Citation
Effects of a dorsal column lesion on somatosensory evoked potentials in primates

Material Information

Title:
Effects of a dorsal column lesion on somatosensory evoked potentials in primates
Creator:
Makous, James Carl, 1963-
Publication Date:
Language:
English
Physical Description:
vii, 171 leaves : ill. ; 29 cm.

Subjects

Subjects / Keywords:
Ankle ( jstor )
Electrodes ( jstor )
Evoked potentials ( jstor )
Lesions ( jstor )
Mental stimulation ( jstor )
Monkeys ( jstor )
Primates ( jstor )
Skin ( jstor )
Spinal cord ( jstor )
Thalamus ( jstor )
Cerebral Cortex -- physiology ( mesh )
Department of Neuroscience thesis Ph.D ( mesh )
Dissertations, Academic -- College of Medicine -- Department of Neuroscience -- UF ( mesh )
Evoked Potentials, Somatosensory ( mesh )
Neural Pathways ( mesh )
Spinal Cord -- physiology ( mesh )
Spinal Cord Injuries -- physiopathology ( mesh )
Genre:
bibliography ( marcgt )
non-fiction ( marcgt )

Notes

Thesis:
Thesis (Ph.D.)--University of Florida, 1993.
Bibliography:
Bibliography: leaves 164-170.
General Note:
Typescript.
General Note:
Vita.
Statement of Responsibility:
by James Carl Makous.

Record Information

Source Institution:
University of Florida
Holding Location:
University of Florida
Rights Management:
Copyright [name of dissertation author]. Permission granted to the University of Florida to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Resource Identifier:
002328727 ( ALEPH )
54535021 ( OCLC )
ALT2371 ( NOTIS )

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Full Text











EFFECTS OF A DORSAL COLUMN LESION ON SOMATOSENSORY EVOKED
POTENTIALS IN PRIMATES











By

JAMES C. MAKOUS


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN
PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF DOCTOR OF PHILOSOPHY


UNIVERSITY OF FLORIDA


1993















ACKNOWLEDGMENTS


I would like to thank my advisor, Charles Vierck, for

taking me into his laboratory at such a late stage in my

graduate education and for his patience and support of my

sometimes unorthodox ideas and experiments. I also thank

the members of my ever-changing committee, David Green,

Bruce Hunter, Richard Johnson, Christiana Leonard, Louis

Ritz and Barry Whitsel, for their critical evaluation and

support of my research. I thank William Luttge for his many

hours spent in making this a better department, John

Middlebrooks for his support during the early stages of my

training and the Center for Neurobiological Sciences for

financial support.

I would also like to thank Jean Kaufman for teaching me

to handle and care for monkeys; Anwarul Azam for keeping the

computers on-line; Carol Martin-Elkins for teaching me basic

histology. I thank Laura Kasper, James Murphy, Anita Puente

and Karl Vierck for technical expertise. I also thank

Robert Friedman, Diana Glendinning and Douglas Swanson for

their support, advice and camaraderie during all the stages

of my education. I am especially indebted to Robert

Friedman for his generosity in sharing his time, knowledge,















laboratory space and equipment all of which were in short

supply (save for his knowledge). I also thank Babbette

Botchin and Dan Thiel for expert veterinary care.

Last, I would like to thank my family; my father whose

advice both personal and professional has never steered me

wrong; and my wife, Elizabeth, who has been an endless

source of love, support and inspiration during these years

of training.


iii















TABLE OF CONTENTS


Pg

ACKNOWLEDGEMENTS........................................

ABSTRACT.................................................

CHAPTERS


age

ii

V


1 GENERAL INTRODUCTION......................... 1

Behavior.......................................... 2
Anatomy and Physiology.......................... 3
Plasticity.................................... 10
Evoked Potentials ............................. 12
Overview of Dissertation..................... 13

2 RECORDINGS FROM THE WHITE MATTER TRACTS
OF THE SPINAL CORD ............................ 15

Methods......................................... 16
Results ....................................... 22
Discussion.................... ...................* 38

3 RECORDINGS FROM THE CEREBRAL CORTEX............ 42

Methods....................................... 44
Results......................................... 54
Discussion.................... ................ 112

4 PHYSIOLOGICAL CHANGES DURING RECOVERY FROM
A DORSAL COLUMN LESION....................... 119

Methods.............. ......................... 120
Results....................................... 123
Discussion............ .................. ...... 150

5 GENERAL DISCUSSION............................. 155

Neural Mechanisms.............................. 155
Conclusions............................. ....... 163

REFERENCES .............................................. 164

BIOGRAPHICAL SKETCH ...................................... 171

iv















Abstract of Dissertation Presented to the Graduate School of
the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy



EFFECTS OF A DORSAL COLUMN LESION ON SOMATOSENSORY EVOKED
POTENTIALS IN PRIMATES


By

James Carl Makous


May 1993



Chairperson: Charles J. Vierck, Jr.
Major Department: Neuroscience


A dorsal column (DC) lesion has a significant lasting

effect on behavioral tasks that require temporal processing

of tactile information (i.e. frequency and duration

discrimination). These experiments describe physiological

correlates of the behavioral deficits in temporal

discrimination observed in primates following DC lesions.

In experiment 1, compound action potentials were

recorded from the major ascending white matter tracts of the

cord. These experiments determined the extent to which

different sensory pathways of the spinal cord responded to

high frequency stimulation. At 10 pulses per second (pps)















pathways in the lateral spinal columns were suppressed to

70-80% of their control values, whereas the DCs were not

suppressed at the same frequency.

In experiment 2, epidural evoked potentials were

recorded from implanted electrodes before and after a DC

lesion. In response to mechanical stimulation, the cortical

evoked potential at 10 pps could not be distinguished from

the background activity (noise) following the DC lesion.

The response to electrocutaneous stimulation showed a

frequency-dependent suppression at 10 pps, after the lesion,

that approximated a 20% reduction in amplitude.

In experiment 3, the cortical evoked potential was

monitored over weeks following the lesion. Under some

conditions, there was a significant increase in the

amplitude of a late (90 ms) peak following the DC lesion.

This increase was correlated with behavioral recovery on a

grasping task. There was no significant recovery for the

early peaks (20 and 50 ms).

In summary, a DC lesion caused an overall decrease in

amplitude of the cortical evoked potential. There was a

significantly greater frequency-dependent suppression of

responses to electrocutaneous stimulation at 10 pps

following the DC lesion. The reduction could be explained in















part by the extent to which the spared spinal pathways

followed 10 pps. There also was an increase in the

amplitude of the 90 ms peak during the weeks following the

lesion that was correlated with a behavioral recovery in

grasping, suggesting a cortically mediated phenomenon.


vii















CHAPTER 1

GENERAL INTRODUCTION



Since the early 1900s investigators have attempted to

use clinical findings in patients with compromised dorsal

columns (DC) to infer the role of this pathway in

perception. These observations suggested that a lesion of

the DCs affects the ability of a patient to detect and

discriminate among a variety of tactile stimuli (see Nathan

et al., 1986). However, for most of these patients, the

lesion involved other spinal pathways as well. In other

instances, most or all of the deficits appeared to recover

over time. Nevertheless, there are deficits that are common

to most accounts of DC interruption, and these are related

to processes that required temporal processing of

somesthetic stimuli. For example, tactile direction

sensitivity or the ability to identify letters written on

the hand (graphesthesia) can be affected by such a lesion.

Graphesthesia requires the patient to integrate the stimulus

over a few seconds. It also has been reported that a

repeated tapping stimulus or an object placed in the

patient's hand will fade over time. However, there are

differing accounts with respect to absolute threshold shifts









2

in response to light tactile stimuli and with respect to

recovery from these deficits.



Behavior

Given the ambiguities in the clinical findings,

investigators have attempted to quantify sensory capacities

in animal models, where a lesion can be isolated to an

individual pathway and confirmed histologically. Vierck

(1977), using Von Frey hair stimulation, showed that there

was no threshold shift on the sole of the foot following a

mid-thoracic DC lesion. For a variety of other tasks,

considerable recovery of function has been observed

following a DC lesion. DeVito and colleagues (1964) found

that monkeys had only a transient deficit in weight

discrimination, and Vierck (1966) found no permanent effect

on limb position sense. Levitt and Schwartzman (1966) showed

a transient deficit in two-point discrimination;

discrimination of size and location of tactile stimuli also

recover (Vierck, 1973; Vierck et al., 1983, 1988). For many

years there was no firm evidence of any permanent sensory

deficit following interruption of the DCs. In fact, Wall

(1970, p. 518) was so bold as to say that the DCs are only

'involved in controlling the analysis of messages arriving

over the other somatosensory pathways.'

More recently, tasks that require some degree of

temporal resolution have shown long lasting sensory deficits









3

in monkeys. Vierck (1974) showed that tactile direction

discrimination was hampered for up to 1 year following a DC

lesion, whereas simple detection of movement across the skin

showed only a transient deficit. Later, Vierck et al.

(1985) showed that monkeys trained to discriminate a 10 Hz

tactile stimulus from a 14 Hz stimulus could not

discriminate 10 Hz from 35 Hz following interruption of the

DC pathway, even after extensive retraining (1 yr). Animals

trained on the same task with lesions of the dorsal-lateral

(DL) and/or antero-lateral (AL) columns showed no such

lasting deficit. In a more recent study (Vierck et al.,

1990), normal monkeys could discriminate between stimulus

trains of 3 pulses (at 10 Hz; 200 ms total duration) from

trains of 5 to 7 pulses (400-600 ms duration); however,

following interruption of the DC pathway, the animals could

not discriminate trains of 3 pulses from trains of as many

as 35 pulses. Thus, it appears that tasks requiring

temporal processing of tactile input, at least in a range of

frequencies from 10-35 Hz, depend uniquely upon input from

the DC.



Anatomy and Physiology

When the DCs are compromised, somatosensory information

reaching the cortex must be carried by the remaining

pathways. The only other spinal pathways that are thought

to contribute significantly to perception are long









4

somatosensory pathways (long tracts) in the dorsal-lateral

(DL), and antero-lateral (AL) columns (Vierck, 1984). Long

tracts in the DL column ascend the spinal cord ipsilateral

to the primary afferent fibers (Rustioni et al., 1979),

whereas the AL tract fibers cross the midline near the root

entry level and ascend the spinal cord in the

antero(ventral)-lateral quadrant of the spinal cord,

contralateral to the primary afferent fibers (Trevino and

Carstens, 1975).

The majority of the fibers constituting the DL and AL

pathways have their cell bodies in the dorsal horn, where

there are a number of modulatory influences. For example,

Jimenez et al. (1987) have shown that there are descending

fibers originating in the brainstem reticular formation and

red nucleus that have presynaptic inputs onto cutaneous

primary afferents entering the dorsal horn. Furthermore,

cutaneous information is carried up the cord to the

reticular formation (Salibi et al., 1980) and the red

nucleus (Berkley, 1986) via the DC nuclei. Therefore, a DC

lesion could result in a change in the regulation of

information entering the dorsal horn, owing to a loss of DC

connections with the reticular formation and red nucleus.

There is also evidence that primary afferents synapsing

in the dorsal horn are directly inhibited by cutaneous

stimulation (Wall, 1958; Janig, 1968). For example,

following cutaneous stimulation, there is an inhibition of









5

primary afferents in the dorsal horn lasting greater that

100 ms; however, primary afferents in the DCs show an

inhibition lasting only 25-35 ms (Wall, 1958). Therefore,

since normal neuronal excitability in the dorsal horn can

have a refractory period of more than 100 ms, it is possible

that changes in perception following interruption of the DC

results from a restriction of temporal processing of

cutaneous information in pathways emanating from the spinal

grey matter.

If pathways other than the DCs are to code for touch,

it is important that the pathways arising from the dorsal

horn carry information about non-noxious, natural cutaneous

stimuli as opposed to information strictly from muscle

afferents. Indeed, a number of studies have shown that the

AL and DL tract fibers respond to natural stimulation of the

skin (Willis et al.,1974; 1975; Surmeier et al., 1988;

Downie et al., 1988) and that they contribute to cortical

responses (Andersson et al., 1975). However, few studies

have looked at frequency coding in the AL tract; the stimuli

used in these studies usually involved a static displacement

of the skin or hair.

The DL tract has been studied much less extensively in

the primate than in the cat, and the two species appear to

differ substantially in the size of the DL pathway

(Nijensohn and Kerr, 1975). Thus, the information carried

in this pathway in primates is not well characterized.









6

However, it has been demonstrated in acute monkey

preparations that an SI cortical evoked potential is smaller

in amplitude but still intact (Andersson et al., 1972)

following interruption of the ipsilateral (to the stimulus)

DCs and the contralateral AL tract, sparing only the

ipsilateral DL tract. This result was obtained in response

to light mechanical stimulation of the skin. Although it is

still not clear the extent to which the DL and AL pathways

carry temporal information, it is apparent that both

pathways carry information that is cutaneous in nature.

The DC, DL and AL tracts synapse in the thalamus before

tactile information is transmitted to the cortex, where it

contributes to normal perception. All three long tracts

have converging inputs onto the ventro-basal complex of the

thalamus (Berkley, 1980; 1983), providing sites for

interaction among the various pathways. Indeed, a number of

studies have demonstrated the existence of excitatory and

inhibitory interaction in the ventro-basal complex of the

thalamus (Anderson et al., 1964; Janig et al., 1979; Salt,

1989). These interactions can last from 50 to 500 ms,

depending upon the cells, and are thought to shape the

spatio-temporal profile of responses that are sent to the

cortex. Thus, removal of one of the inputs to this region

(e.g., a DC lesion) could lead to an imbalance between the

remaining excitatory and inhibitory inputs. This could

change neuronal integration (filtering) in the thalamus,









7

which, in turn, could result in a change in perception.

A number of studies have attempted to ascertain the

role of the various spinal cord pathways in generating a

cortical response through evoked potential measurements. In

general the results have been inconclusive, owing to the

variety of stimuli used, the lack of repeated measures

within individual animals, and the different kinds of

anesthesia.

Gardner and Morin (1953; 1957) showed in pentobarbital

anesthetized monkeys that neither chronic nor acute DC

section altered the latency or threshold of somatosensory

cortical evoked potentials. In this study, they used

electrical stimulation directly on dissected cutaneous and

deep nerves. It was not clear how they determined threshold

or the amplitude of stimulation. It is also possible that

direct stimulation of the nerve recruited predominantly the

large diameter fibers originating in muscle (York, 1985).

Eidelberg and Woodbury (1972) also found no change in

the amplitude or latency of the cortical evoked potential

following chronic (>4 weeks) or acute DC or dorsal quadrant

lesions in monkeys. They stimulated the radial nerve

transcutaneously at 1-3 mA under chloralose anesthesia.

Unfortunately, these results were compared to unoperated

controls rather than preoperative controls from the same

animal.

On the other hand, Andersson et al. (1972) recorded









8

evoked potentials from acute Nembutal anesthetized monkeys

and found that there was an increased latency of 4-5 ms and

a decrease in amplitude of about 25% following DC section.

There was no change in the location of maximum activity from

intradermal electrocutaneous stimulation of the foot or the

hand. In the conditions when a mechanical stimulus was

used, the animal had already received a lesion of either the

ventral quadrant or dorsal quadrant before recordings were

made. This made it difficult to ascertain the contribution

of the DCs to the mechanical response.

A more recent study by Cusick et al.(1979) in monkeys

showed, under ketamine anesthesia, that acute DC section

almost completely eliminated the cortical evoked response to

exposed sciatic nerve stimulation. Following a 4-7 week

period after the lesion, there was a small increase in the

amplitude to about 25% of the preoperative control

amplitude. On the other hand, following a lesion of the DL

and AL pathways, sparing the DCs, there was no appreciable

attenuation of the evoked potential. Thus, the conclusion

from these studies is that the DCs provide sufficient input

to support a cortical evoked potential, but intact DCs are

not necessary for the presence of an evoked potential.

A few investigators have also looked at unit responses

following interruption of the DC pathway or dorsal

hemisection. Andersson et al. (1975) found, in lightly

anesthetized pentobarbitall) monkeys, that acute dorsal









9

hemisection of the cord decreased the number of units per

cortical penetration that could be driven by peripheral

stimulation. There was also a high number of units that

were spontaneously active and were driven unreliably. The

latencies of units did not appear to be longer than control

animals, but units were more often found on the hairy than

on the glabrous skin. Although most of the units tended to

be rapidly adapting, they typically could not follow

repetitive stimulation beyond 4 Hz.

These results are in general agreement with the results

of Dreyer et al. (1974), though they differ in the details.

Dreyer et al. found, in awake monkeys with chronic (21-72

days) DC lesions, that fewer numbers of units were driven by

peripheral stimulation, and the responses were less

reliable. In contrast to Andersson et al. (1975), they

found a high proportion of neurons that responded to deep

stimulation rather than light stimulation. There was a

cortical region, corresponding primarily to the center of

the hand and foot representations in areas 3b and 1, that

was nearly devoid of responses following DC lesion, whereas

the surrounding cortical areas (3a and 2) appeared more

normal in the nature and proportion of responses.

Until now the afferents in the fasciculus gracilis (FG)

from the foot have been presented as if they were

distributed in a pattern similar to that of the fasciculus

cuneatus (FC) from the hand. However, Whitsel et al. (1972)









10

found, in recordings from fibers at cervical levels, that

fibers in the FC innervated both cutaneous and deep

structures, whereas the fibers in the FG were predominantly

cutaneous. This is in contrast to recordings made more

caudally, where the fiber types were similar for both the FC

and the FG. This suggests that there is sorting of fibers

from the FG as it ascends the spinal cord, resulting in a

projection of proprioceptive afferents to the dorsal horn

and then the DL tract (Dreyer et al., 1974). Therefore, it

is possible that a lesion of the FG would produce behavioral

effects that differ from those produced by a lesion of the

FC.


Plasticity

A number of recent findings suggest there is some

degree of plasticity in the adult nervous system (see Wall,

1988 for review). For example, the results of Merzenich et

al. (1984) have shown in recordings from anesthetized

monkeys that the cortical representation of the fingers

adjacent to an amputated finger included the region of

cortex formerly dominated by input from the missing finger.

These changes in the borders of the cortical representation

were on the order of 1-2 mm and appear to represent an

unmasking of inputs that are normally suppressed by the

anesthesia. More recently, Pons et al. (1991) found that

long term (> 12 yrs) dorsal rhizotomy (C2-T4; C = cervical;









11

T = thoracic; L = lumbar) produced large (> 1 cm) changes in

the area and location of cortex represented by the face

relative to control animals. That is, the face

representation invaded the area normally occupied by the

hand. It is not clear where the actual reorganization took

place; however, given the large shift in the cortical map, a

cortical mechanism is unlikely. A more likely locus could

be the spinal cord or thalamus, where the representations of

adjacent body parts are in closer proximity.

Rausell et al. (1992) also looked at the thalamus of

the monkeys used in the Pons et al. (1991) study. They

found a down regulation of gamma-aminobutyric-acid (GABA)

receptors in the deafferented thalamus relative to controls.

They also found changes in calcium binding proteins that are

specific for either lemniscal or nociceptive pathways.

Thus, it appears that there were long term changes in the

thalamus that accompanied the reorganization of the map at

the cortical level.

Changes in spinal cord have also been observed

following deafferentation. For example, Goldberger and

Murray (1982) observed sprouting in the cord following

dorsal rhizotomy in cats. They found an increased

projection to nucleus gracilis and to the spinal laminae

that normally received projections from the spared root.

However, there was no sprouting into areas not normally

receiving projections from the spared root. There also was









12

a tendency for areas that are topographically organized to

not receive any sprouting fibers.

Thus, it appears that neural plasticity does exist in

the adult nervous system, and it is possible that changes

following injury to the brain or spinal cord could be taking

place at many possible points along the neuraxis. It is

likely, then, that a behavioral recovery following a lesion

could reflect changes in the neural connectivity in the

spared pathways.



Evoked Potentials

Evoked potentials are the summated neural response from

a group of neurons depolarizing and/or hyperpolarizing in

synchrony. The amplitude of the evoked potential is

proportional to stimulus amplitude under some stimulus

conditions (Beck and Rosner, 1968; Franzen and Offenloch,

1969; Kulics, 1982); however, this issue has been disputed

(Uttal and Cook, 1964; Schwartz, 1976). Evoked potentials

are often used as a diagnostic tool for the integrity of the

afferent pathways (Pillay, 1984). The first positive peak

in the somatosensory cortical evoked potential is thought to

arise from the depolarization of layer four (a current

sink), whereas the current source arises from the dendrites

at the surface of the cortex. The second peak (negative)

arises from a local spread of activity into immediately

adjacent cortex. The source is layer four and the sink is









13

the cortical surface where axons are contacting dendrites.

The second positive peak is derived from a more global

spread of information to association cortices. In this

condition, the SI cortex serves as a source and the other

cortical areas serve as sinks. This late positive potential

can be recorded over a large area of cortex (Arezzo et al.,

1981; Kulics and Cauller, 1986; Emerson and Pedley, 1990;

Allison et al., 1991).



Overview of Dissertation

The following chapters describe a series of experiments

that were designed to look at the effects of a DC lesion on

somatosensory evoked responses to repetitive stimulation.

These experiments describe physiological accompaniments of

the temporal discrimination deficits observed following such

a lesion. The second chapter looks at the extent to which

compound action potentials recorded in the three long spinal

tracts follow high frequency stimulation. It was expected

that such an experiment would provide evidence concerning

the origin of any frequency-dependent suppression that might

be obtained at the cortical level in the absence of the DC

pathway. The third chapter describes changes in the evoked

cortical response and its frequency-dependent suppression

following the DC lesion. The fourth chapter follows the

evoked potential as it changes over months following the

lesion. This experiment was designed to correlate changes









14

in the cortical evoked potential with behavioral changes

observed in animals recovering from DC lesions. The last

chapter discusses some possible mechanisms for the changes

in the cortical evoked potential that accompany DC

interruption.














CHAPTER 2

RECORDINGS FROM THE WHITE MATTER TRACTS OF THE SPINAL CORD



Following a DC lesion, the remaining pathways that

contribute to perception are the DL and AL tracts (Vierck,

1984). Where there is a deficit in an animal's behavior

following such a lesion, there must also be a deficiency in

the capacity of the spared pathways to carry the neural

information necessary for the animal to perform the task.

For example, interruption of the DC pathway leads to

deficits in frequency discrimination at frequencies above 10

pps and in duration discrimination for trains of pulses at

10 pps (Vierck et al., 1985; 1990). Thus, it is likely that

the spared pathways can not reliably carry these kinds of

information at frequencies of 10 pps or greater.

There is reason to believe that the spared pathways

emanating from the dorsal horn grey matter are subject to

modulatory influences. For example, cutaneous stimuli

suppress the responses to stimuli less than 100 ms later in

the dorsal horn (Wall, 1958). In addition, Jimenez et al.

(1987) have demonstrated presynaptic influences originating

in the brainstem and terminating on primary afferents

entering the dorsal horn. Thus, either one of these









16

mechanisms could regulate the extent to which spared

pathways contribute to perception.

It was this line of reasoning that led to the first set

of experiments. If the pathways emanating from the dorsal

horn were dramatically suppressed at 10 pps, then the dorsal

horn could be a neural locus of the behavioral deficit

observed following DC interruption. Therefore, experiments

were undertaken to record from the white matter tracts of

the cord in response to different stimulus frequencies, and

the extent to which each pathway was suppressed by

increasing frequencies was determined.



Methods



Animals

The subjects were three female macaques (1 Macaca

arctoides and 2 Macaca nemestrina) that weighed between 4.8

and 11.4 kg. They were housed in an outdoor communal

enclosure to maximize the animals' health and psychological

well being. The animals were maintained on a diet of Purina

monkey chow, fruit and water. Prior to the acute

experiments, these animals were used in two procedures: a

behavioral study in which they received a cortical lesion of

the arcuate gyrus, and an anatomical study in which they

received an injection of HPR into the lumbrical muscles of

each hand, one week prior to the acute experiment. Two









17

months prior to the acute experiment, one animal (monkey E)

had a surgical interruption of the dorsal column on the

right side between Til and T12 (see Histology). This

procedure was conducted under sterile surgical conditions by

Dr. C. J. Vierck, Jr. (see Chapter 3 Methods for details).

Preparation. Each animal was premedicated with

intramuscular (i.m.) ketamine HCL (100 mg) and atropine

sulfate (.54 mg), given intravenous (i.v.) fluids lactatedd

Ringers) and then intubated. Isoflurane anesthesia was

passed to the animal and maintained at a level of 1.5-2.5%

throughout the remainder of the experiment. Each animal's

core temperature was monitored with an esophageal

thermometer and was maintained between 37 and 38 degrees C

with a heating pad (K-pad) and warmed paraffin bags. The

back of the animal was then shaved and a rostral-caudal

incision was made over the low thoracic vertebrae. The

muscle and fascia were scraped away from the dorsum of 4 or

5 vertebrae, and 2 or 3 of the dorsal laminae were removed

with rongeurs. The underlying fat and connective tissue

were dissected away, exposing the dura mater. A rostral-

caudal slit was made in the dura, and it was reflected to

expose the pia. The cord was then bathed in warm (37

degrees C) mineral oil. The remaining two spinous processes

at the rostral and caudal extent of the exposure were then

clamped and suspended by a stereotaxic frame.

Stimulation and recording. Each foot was stimulated









18

electrocutaneously at the tibial nerve, posterior to the

medial malleolus at a current sufficient to elicit a small

twitch of the first toe (ca. 5 mA). The duration of each

pulse was 0.2 ms, and the frequency of stimulation was

varied systematically from 1.5 pulses per second (pps) to 50

pps. Stimulating electrodes consisted of silver/lead solder

molded into a small bead 4 mm in diameter. The anode and

cathode were separated by 2 cm (cathode proximal),

lubricated with sergi-lube and held in place with adhesive

pads and tape. The animal was grounded with a ring

electrode placed around each calf proximal to the

stimulating electrode.

Compound action potentials were recorded from the white

matter tracts of the spinal cord by lowering tungsten

electrodes into the cord with a X-Y-Z micro-positioner.

Tungsten electrodes were made by immersing a tungsten rod

(0.007 in. diameter) into a bath of saturated sodium nitrite

and passing an AC voltage (ca. 6 volts) between the tungsten

and a carbon rod, also in the bath. The tungsten was then

slowly removed from the bath, and, in this way, a blunt

point was etched onto the end of the electrode. The

sharpened end of the tungsten was then passed through the

back end of a glass micro-pipette. The tip of the pipette

was broken to allow about 1 cm of exposed tungsten. The

tungsten was held in place by dental wax, and the entire

exposed tip of the electrode was dipped in Insl-x









19

(insulation). The tip of the electrode was then briefly

touched against a hot soldering iron. This usually yielded

impedances in the range of 10 100 kohms (at 1000 Hz),

depending on the duration of contact with the hot iron.

Signals recorded in the spinal cord in response to

electrocutaneous stimulation were differentially amplified

(Bak, 10,000x) in reference to a muscle flap along the

margin of the surgical opening. The signals were digitized

(11 us, Vetter), and recorded on magnetic tape (VCR) for

off-line analysis. The signal was also filtered (3-300 Hz

pass-band) and averaged on-line (286-computer; RC

electronics software) to monitor the potential during each

recording session.

Procedure. The experimental procedure consisted of the

following. The electrode was lowered into each of the major

tracks of the cord after visualizing the dorsal root entry

zone and the midline under a dissecting microscope. For

dorsal column penetrations the electrode was positioned

sufficiently near the midline to evoke a large response to

ipsilateral stimulation of the foot without evoking a

response from the contralateral foot. Dorsal-lateral

penetrations were made slightly lateral to the dorsal root

entry zone and were shallow enough to record little or no

response from stimulation of the contralateral foot.

Antero-lateral penetrations were made slightly more lateral

and deeper than the DL penetrations, to maximize a response










to contralateral stimulation. These locations often

produced an ipsilateral response that was less than 40% the

amplitude of the contralateral response.

After an electrode was placed in one of the tracts by

one of the above functional definitions, a frequency series

was conducted. In the case of the DC and DL tracts the

ipsilateral foot was stimulated, whereas the contralateral

foot was stimulated for the AL recordings. These three

stimulus conditions will be referred to as stimulation of

the experimental foot, whereas stimulation of the non-

experimental foot will be referred to as stimulation of the

control foot. Each frequency series consisted of 100-150

sweeps by the averaging software over a sweep duration of 75

ms. Thus, for the higher frequencies, the animal received

more stimuli (i.e. at 1.5 Hz there was 1 stimulus/sweep and

at 50 Hz there were 3 stimuli/sweep). The stimulus sequence

was typically as follows: experimental foot (at 1.5, 2.5,

5.0, 7.5, 10, 25, 50 and then 1.5 Hz), control foot (1.5

Hz), and experimental foot (1.5 Hz).



Data analysis

The data were analyzed off-line. "Raw" evoked

potential records were read off magnetic tape, band-pass

filtered (3-300 Hz), digitized (300 us bin width) and

averaged by commercially available software (RC

electronics). The 75 ms long averages were converted into











ASCII files and saved on disk. ASCII files were imported

into a spreadsheet, where latencies and amplitudes could be

computed. Latency was computed from the peak of the

stimulus artifact to the peak of each distinct waveform.

The peak amplitude of the potential was computed by taking

the difference between the amplitude 6 ms after the stimulus

artifact and the amplitude at the mean latency of the peak.

The response amplitudes at each frequency were expressed as

a percentage of the amplitude of the response to stimulation

of the experimental foot at 1.5 Hz (referred to as the

standard amplitude).



Histology

At the end of each experiment the animals were given an

overdose of pentobarbital (195 mg i.v.). They were then

perfused through the heart, first with warm (37 degrees C)

phosphate buffer (7.4 pH) and heparin sulfate (1 units/L),

then with fixative (2.5% glutaraldehyde and 2.0%

paraformaldehyde). This was followed by a mixture of

fixative and 10% glycerol and then rinsed with 10% glycerol

in phosphate buffer. The spinal cord was removed from C2

down to LI; the dorsal roots were counted, and the cord was

blocked 2 levels rostral and caudal to the recording

exposure. In the animal with the DC lesion, the cord was

blocked rostral and caudal to the lesion as well. The cord

was cryo-protected in a 10% formalin and 30% sucrose (or









22

glycerol) solution for a minimum of 1 week. Transverse

sections were cut on a freezing microtome at 50 um, mounted

on slides and let dry for a minimum of 1 day. They were

then stained (cresyl violet) and cover-slipped (Permount).

The extent of the DC lesion was drawn, and the electrode

tracks were reconstructed.



Results



Histology

The locations of the recording electrodes were verified

histologically in all recordings. Each of the recording

sites for each animal is shown in Figure 2-1. The DC

recordings were typically near the midline and in the

ventral half of the DCs. In one animal (monkey K), the

recording site bordered the grey matter. The DL recordings

were usually confined to the DL quadrant but occasionally

bordered the ventral quadrant of the cord. The AL

recordings were usually ventral to, but occasionally

bordered, the DL quadrant. During the AL recordings it was

often difficult to eliminate the response from the control

foot, especially at 11 ms.

The DC lesion in monkey E was between Til and T12 and

is shown in Figure 2-2. There was complete interruption of

the right DC at this level. There was very little

involvement of the left DC or the grey matter and no

encroachment into the right DL.











Spinal Recordings

Table 2-1 shows the peak latencies obtained for each

animal in each tract, averaged across all frequencies. The

'n' column corresponds to the number of frequency series

that were conducted in that tract for that animal. Monkey E

received a right DC lesion more than 2 months prior to the

recordings. Note that the AL response had two peaks that

differed in latency by 3 ms in two of the three animals.

There was a tendency for potentials evoked in the post-

synaptic pathways to have a slightly longer latency (0.3 4

ms) than the DC pathway.

Representative averaged responses from each tract are

shown in Figures 2-3, 2-4 and 2-5. These were derived from

one animal (Monkey D) on three separate penetrations. The

response from the DC (Figure 2-3) had a latency of 9.6 ms

and showed little suppression with high frequency

stimulation. There was almost no DC response from the

control foot. The response from the DL tract (Figure 2-4)

had a latency around 10.1 ms, but showed a more pronounced

suppression with increasing frequencies. At 50 pps the

potential was little more than 50% of the standard response

to 1.5 pps. The response from the control foot was small.

The AL tract had the most complex response (Figure 2-5).

The pll response was suppressed to nearly 50% at 10 pps,

whereas the p14 response was not substantially suppressed

until 25 pps. However, the p14 was completely abolished at









Figure 2-1. Electrode recording locations from the
spinal cord white matter of three monkeys. All
recording sites are drawn on a standard mid-thoracic
(T8) section. Black ovals represent approximate
recording locations, while dashed lines connect
recordings sites within one electrode penetration.
Often, two frequency series were recorded at the
electrode location. Abbreviations as in text.





25






D L B ,o D L
64DL DL
DL

e#&I
AL


Monkey K


DC
4 DC DL
D LD
L\ ) I DL \
AL 0

AL


Monkey E


DC


DLDL
DOD
DLAL o A D
D AL A'
AAL
Moe D AL6

Monkey D

















0) C
.0 0 0
-r4 M

1 -4

o 0

o






-4
4 *) 0





0o


-H 0
o r.
0 0
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0 4J














-4M 4-I (1)


*4*


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>
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0 m




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Ec 0
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00 M





c a)







mu- U)


C6


0 0
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cIq


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5 );


co


- Jn
0 E,


00


00


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0;05 -a0C
V- l IIv- v


Ci


00


QE oio


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0
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110
0


0) -W
>-'
(UCe









Figure 2-3. Compound action potentials recorded from
the DC of monkey D. (TOP) The responses to different
frequencies of ipsilateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the contralateral (control) foot at 1.5
pps expressed as percentage of the ipsilateral response
at 1.5 pps.

















Spinal cord recordings
dorsal column


pps


50 pps


10 15


control
foot


- -


1.5 pps


100



80



60



40


20-


- .


I I I I I I I I I I I I Il li
5 10 15 20
time (ms)


-* "^









Figure 2-4. Compound action potential recordings from
the DL tract of monkey D. (TOP) Responses to different
frequencies of ipsilateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the contralateral foot at 1.5 pps.


















Spinal cord recordings
dorsal-lateral


1.5 pps

5 pps-


pps


25 pps


50 pps.


10 15


/" \ /


/, -- j


100



80



60



40


-20


control
foot


I


5 10 15 20
time (ms)









Figure 2-5. Compound action potentials recorded from
the AL tract of monkey D. (TOP) Responses to different
frequencies of contralateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the ipsilateral foot at 1.5 pps.




















Spinal cord recordings
antero-lateral


p1 1


1.5 pps


pps


50 pps


", 10 pps


10 15


control
- foot


-1 a .


10 15 20
time (ms)


100


0
CL
4-0



C.
0
0


20-


! I

















r-4 4) W 0\P r (U
(0 Lt 0 in --4 r.
. (0-4 4J I4
naM n C
2~H 000
w w 0 0 0
. 1)W 0
4J r '
PE- 0 4-J 4-)

0 W a 0


C '0 E-4
O W 0G

+1 0
*"" + 14 *





0 04




" ~4 I W & .
0W 0 0

o0 0
"3 W CM 0
r (- H w1



0 0 0 -H

0 W 4 M M
rq 41 3 ,


0 w r. 3O
aO ) p to



04> 0 0r. r



0 o0 P 0 4j







Pi4 U 0 4J1 4J 4J> U













,- L






-O00


OCCx


/
/


NW I
/
/ 1


I --x


/
/


Q 1
Q_





-co
-to
-CM (I)


0
0

(sdd


I


g'I "lOJ1,uoo


%) pnl!;dLuv


I I


I









37

50 pps, whereas the pll was not. Moreover, the p14 appeared

to shift its latency at 25 pps, which suggests the existence

of yet a third peak that was unmasked at 25 pps. Both

animals with a p14 response exhibited this phenomenon. The

pll response from the control foot was 20% of the standard

response to stimulation of the experimental foot, which was

not uncommon for this electrode location.

Averaged (across animals) frequency-response functions

for each of the tracts are shown in Figure 2-6. The most

obvious result was that responses from the DL and AL columns

did not follow the 50 pps stimulus as well as the potentials

within the DC pathway. However, at 10 pps the late response

from the AL tract (pl4) was not significantly different from

the DC response. In fact, there was even a slight (but not

significant) augmentation of the p14 response at 2.5 pps.

Beyond 10 pps, however, there was a precipitous drop off in

the response at p14 to higher frequencies. The AL response

at pll showed a similar trend to the response from the DL

tract at the low frequencies, but beyond 10 pps the two

functions diverged. The DL response was never suppressed to

more than 70% of control at the highest frequencies, whereas

the pll response from the AL tract at 50 pps was down to 20%

of the standard amplitude.



Summary

In response to electrocutaneous stimulation of the









38

tibial nerve, the DC pathway showed a significantly (p<0.05)

smaller suppression than any other subdivision of the spinal

cord, at stimulus frequencies of greater than 10 pps. At 10

pps or less, the three tracts were suppressed by nearly

comparable amounts. At 10 pps, suppression of the p14

response from the AL tract was not significantly different

than the DC suppression. On the other hand, the DL and the

AL (pll) responses were significantly (p<0.05) more

attenuated at 10 pps than the DC response.



Discussion



The principal result of this study was the observation

that ascending pathways in the lateral columns, which

emanated from the dorsal horn, are not profoundly suppressed

by repetition rates up to 10 pps. Therefore, behavioral

deficits in detection of 10 pps stimulation after

interruption of the dorsal columns are unlikely to be

attributed to a suppression of input to supraspinal targets

of pathways in the DL and AL tracts. At 10 pps, where the

tracts respond at 70% of the standard response or greater,

it is possible that any one of the pathways could contribute

significantly to the perception of a 10 pps stimulus.



Latency

The relative latencies of responses within the three









39

tracts was as expected. The DC pathway had the shortest

latency to peak (10.3 ms), whereas the DL and AL had longer

latencies (10.7 and 10.8 ms, respectively). Since these

latter two pathways comprise post-synaptic populations of

fibers and do not include primary afferents (in contrast to

the DC), it follows that longer latency responses were

obtained from the lateral columns. The AL and DL responses

should be nearly 1 ms later than responses from the DC,

given the mandatory synapse (i.e. delay of 1 ms) in the

dorsal horn. It is possible that a combination of factors

contributed the 0.5 ms difference actually observed. For

one, the DC response from monkey E was about 1.5 ms longer

than the DC response from the other two animals. Since the

DCs also have a large number of post-synaptic cells arising

from the dorsal horn (Rustioni et al., 1979), it is possible

that this recording was made from a division of the DC with

a preponderance of post-synaptic fibers. Since there was a

DC lesion in monkey E on the contralateral side, responses

arising from the control foot were not a determining factor

for this electrode placement, as it could have been in the

other recordings. Another factor that could have

contributed to the small difference between the DC and AL

latencies was the large bin width of 0.3 ms.

In addition to peaks at 11 and 14 ms, there was a peak

at 15 ms that appeared only at 25 pps in the AL response,

but it was abolished at 50 pps. It is possible that this









40

peak was derived from a third group of fibers in the AL,

given its different latency and unique frequency

sensitivity.

One animal (monkey K) showed no appreciable pll

response in the AL tract. It is not clear why this

occurred, since the recording electrode in this animal did

not appear to be in a substantially different location than

the other two animals. It is possible that the high

electrode impedance (100 kohms) used in this animal drew

from a smaller population of fibers than the electrodes used

in the other two animals (15 and 65 kohms).



Frequency Response

The DC response showed less suppression than the other

two tracts at all frequencies above 10 pps. This result was

not unexpected since the DL and AL tracts do not contain

primary afferent fibers. Because each synaptic delay tends

to decrease the reliability of high frequency transmission,

the DC should be better equipped to carry high frequency

information up the cord. Conversely, one could argue that

the AL and DL tracts do carry high frequency information,

but it is lost in the averaged response, owing to a variable

latency of individual responses. If this were the case, one

would expect to see not only a decrease in the amplitude of

the response at high frequencies, but also a broadening of

the peak at high frequencies. This was not observed in

either the DL or the AL tracts.











Summary

These experiments demonstrated, through compound action

potentials recordings from large populations of spinal

fibers, that the extent of suppression for the different

pathways at 10 pps is similar. In the most extreme case,

the AL pll response was 70% of standard amplitude in

contrast to no suppression for the DC response (100% of

standard). Thus, it is likely that the pathways spared of a

DC lesion could reliably carry 10 pps stimulus up the cord.

However, at 50 pps there were large differences in the

frequency-dependent suppression of different pathways.

If any of the long spinal tracts were to be compromised

in some way (i.e. by a lesion), it is possible that, at the

cortex, there would be a decreased response amplitude,

because some percentage of the input to cortex was lost. It

is also possible, given the small difference (ca. 20%) in

slope between the DC and other pathways, that there would be

a concomitant change in slope of the frequency-response

function at the cortex following a DC lesion. If these were

indeed the outcomes of cortical recordings, then the animal

in a behavioral task might require a larger stimulus for

detection and could reveal an alteration in threshold with

stimulation frequency.














CHAPTER 3

RECORDINGS FROM THE CEREBRAL CORTEX



Following a DC lesion, the information arriving at the

cortex is limited by the extent to which the spared pathways

(DL and AL) carry somatosensory information and by the

responsivity of partially deafferented central relays of the

spared input. Since there are behavioral deficits in

discrimination of repetitive stimulation at frequencies of

10 pps and above, it should be instructive to look at

cortical responses to 10 pps before and after a DC lesion.

There are several possible outcomes of these recordings:

1) It is possible that, following a DC lesion, the

cortical evoked potential is diminished in amplitude.

Although this has been the subject of some dispute (see

Chapter 1), it is likely that a removal of one of the long

tracts would result in the diminution of the overall amount

of input to cortex. This result would suggest that an

elevation of detection thresholds could be seen following

the lesion. However, this has not been found with

application of von Frey hairs to the sole of the foot

(Vierck, 1977) or with brush stimuli to the lateral calf

(Vierck, 1974). Thus, it appears that input from infrequent









43

stimulation (e.g., von Frey hairs or brush stimuli) gains

access to the cortex more effectively than input which has

been preceded by recent stimulation (e.g., train of pulses).

2) It is possible that, following a DC lesion, there

is a change in the extent to which the entire cortical

evoked potential is suppressed by increasing frequency.

This result would suggest that information transmitted to

the cortex over the spared pathways is compromised by the

capacity for these alternate pathways (or partially

deafferented relays) to follow a 10 pps stimulus. Such a

frequency-dependent suppression of early and late peaks

would suggest that the locus of the effect is sub-cortical:

either at the dorsal horn or thalamus.

3) It is possible that, following the lesion,

different peaks in the cortical evoked potential would be

suppressed by different amounts, either in absolute

amplitude or in frequency-dependent suppression. For

example, it is possible that the first peak of the evoked

potential, which is associated with the depolarization of

layer four, would show no change in amplitude or frequency-

dependent suppression. If only the later peaks, associated

with the spread of information that arose from layer four,

showed an effect of the lesion, this would suggest that the

pathways spared by the lesion adequately carry the

information to the cortex, but that there are changes at the

cortical level following deafferentation that affect the









44

animal's ability to perform the task.

The above reasoning led to the experiments below. The

idea was to determine changes in the cortical evoked

potential following a DC lesion. In this way, the neural

mechanisms underlying the behavioral deficit might be

ascertained.



Methods



Chronic Recordings



Subjects and Training. The subjects were three female

Macaca arctoides (stumptailed macaques) that weighed between

8.6 and 11.3 kg. These animals were not used in the acute

spinal cord experiments. The animals were housed in an

outdoor communal enclosure to maximize their health and

psychological well being. They were tested five or six days

a week. Each day the animals were led into the laboratory

on a leash and seated comfortably in a plexiglas primate

chair. They were gradually trained to tolerate gentle

restraint of their wrists and ankles by leather straps. In

the chair, apple sauce was dispensed through a tube in

response to the animal pressing a bar. After 10-15 min in

the chair, each animal was returned to its home "run" for

the normal diet of Purina monkey chow, fruit and water (ad

libitum).









45

Surgery. Following chair training, epidural recording

electrodes were implanted over primary somatosensory cortex

(SI). This was done under sterile conditions at the

University of Florida animal surgery facility. The animals

were premedicated with ketamine HCL (100 mg) and atropine

sulfate (0.54 mg) before intubation; then Halothane

anesthesia was administered and maintained at 1.5-2.0%.

During the implantation, the skull was exposed, the

bone was cleared of muscle and fascia, and 10 surgical

grade, stainless steel bone screws were implanted. Five

screws were placed over each SI foot representation, in 3-4

mm increments along (3 mm lateral to) the midline (see

Figure 3-1). The stereotaxic coordinates were chosen so as

to cover and flank the foot representation on each side.

Two or four reference electrodes were also implanted over

each frontal lobe. A teflon coated platinum-iridium wire

(Medwire) was passed from the head of each screw to a

miniature D-25 connector that was encased in dental acrylic,

along with the implanted screws. The skin flaps were closed

to cover the skull not covered by acrylic. The animals were

given antibiotics (Dualpen, i.m.) for 1 week following the

surgery and Torbutrol (0.5mg/6hrs) for pain.

Another surgery was performed after normal (pre-lesion)

evoked potential recordings were collected from each animal

(typically for 2 months post-implant). During this surgery,

a unilateral fasciculus gracilis lesion was made by Dr. C.J.









46

Vierck, Jr. (sponsor) at a mid-thoracic level. A

laminectomy was performed on 2 mid-thoracic vertebrae; the

dura was pulled aside, and the dorsal cord was exposed. The

cord was visualized with a microscope, and the dorsal white

matter was interrupted with precision forceps between the

midline and the root entry zone on one side. The incision

was closed, and each animal was given antibiotics (Dualpen,

i.m.) for 1 week following the surgery.



Recording. The animals were seated in a primate chair

that provided loose restraint of the arms, legs and abdomen.

The male D-25 connector on the head was mated with a female

D-25. The female connector was connected, via individually

shielded cables, to a manual switch box located on the wall

adjacent to the animal. The switch box allowed a choice

between any reference electrode, located over frontal

cortex, and any "active" electrode over SI cortex. The two

outputs from the switch box were differentially amplified

(Bak; 10,000x), digitized (Vetter), and recorded on magnetic

tape (VCR) for off-line analysis. The signal was also

averaged on-line (286-computer; RC electronics software) to

monitor the evoked potential during each recording session.

Stimulation. While in the primate chair, the sole of

each foot was stimulated either electrocutaneously or

mechanically. An S88 stimulator (Grass) generated the

stimuli. The stimulus frequencies typically ranged from 1.5









47

pps to 10 pps for both electrocutaneous and mechanical

stimuli. The number of presentations of each stimulus

condition varied from 64-320, depending upon the stimulus

frequency.

For the electrocutaneous stimuli, the output of the S88

passed through a stimulus isolation unit, a constant current

unit, a current monitor, and then out to the animal. Each

animal received stimulation of the foot via two wells in

adhesive foam pads that were filled with either Sergi-lube

or electrode paste. The amplitude of stimulation (4 mA) was

chosen so as to elicit a recognizable evoked potential

without causing any discomfort to the animals or a

perceptible muscle twitch. The duration was short (0.2 ms)

to minimize the stimulus artifact. Two animals received

electrocutaneous stimulation of the ankle with ring

electrodes made of aluminum foil. Each 3/4 in. strip of

foil was coated on one side with sergi-lube, wrapped around

the ankle or the calf, and held in place with adhesive tape.

Stimulus amplitude was 12 mA, which caused a slight twitch

of the foot during about half of the recording sessions.

Mechanical stimulation was provided by a vibrator (Ling

102) that was driven by a locally designed and constructed

driver that took the voltage output of the S88 (a 10 ms

pulse) and matched it to the current requirements of the

vibrator. The vibrator was mounted on a track that could be

vertically advanced by turning a screw with a 1 mm pitch. A









48

9 mm diameter probe, mounted on the end of the vibrator,

passed up through a linear voltage displacement transducer

(LVDT; Schaevitz) and then through a 1.9 cm hole drilled in

a plexiglass foot rest. The monkey's foot was held in place

by a polyform cast, such that the thenar eminence of the

foot was directly over the 1.9 cm hole. The probe was

advanced to make a 1-2 mm indentation in the skin. The

stimulus amplitude was calibrated to 0.4 mm, monitored

(LVDT) throughout each session on an oscilloscope, and saved

on magnetic tape.



Data analysis. All data were analyzed off-line. The

"raw" evoked potential records were read off tape, low-pass

filtered (100 Hz), and digitized (1000 Hz, 1 ms bin width)

by commercially available software and an A-D board (RC

Electronics). The digitized records were converted into

ASCII files for further analysis by software written in 'C'

(by the author).

The averaged evoked potentials were constructed first

by discarding any traces that fell outside of a user

specified amplitude window (typically 300 uV). This was

intended to reject evoked potentials that contained movement

artifact. The remaining traces from an individual session

were then averaged, and the standard deviation (SD) was

computed for each time point (bin) in the average. Averaged

data from individual days were combined into averages across









49

blocks of days with similar stimulus conditions, and

comparisons between pre-lesion and post-lesion data were

based upon these blocked averages. To compare the evoked

potentials recorded under different conditions, the peak-to-

peak amplitudes of p20-to-n50 and n50-to-p90 were computed

(see Figure 3-3). This was done to avoid problems presented

by a fluctuating baseline, especially at different stimulus

frequencies and after the DC lesion, when baseline

fluctuations approached the amplitude of the evoked

potential.

Estimates of baseline levels of noise were made by

calculating the mean amplitude and variance of the

recordings obtained during the 250 ms before each stimulus

onset at 1.5 pps. This was done by taking a random sample

of 1 ms bins. Each sample was taken from a 10 ms window,

once every 20 ms. This procedure yielded results that did

not differ significantly (p<0.05) from sampling once every

50 ms (at 50 ms the autocorrelation function was zero).

However, this technique provided a better estimate of the

noise by increasing the number of samples.

The statistical analyses were all done by programs

written in 'C' by the author. A t-test was used to identify

significantly different slopes and y-intercepts (Mendenhall

et al., 1986; pg. 464) for functions relating response

amplitude to stimulus frequency. This was done first by

fitting a linear (least-squares-fit) function to the data.









50

Then, the mean and variances of the estimates of the slope

and y-intercept were used to compute the test statistic 't.'

This was a conservative test.



Acute Recordings



Animals. Acute recordings from SI cortex were obtained

from three female stumptailed macaques, two of which were

used in the awake experiments above, and three female rhesus

monkeys (Macaca mulatta). The rhesus monkeys were

previously used in behavioral experiments in vision, and had

received horseradish peroxidase injections in small muscles

of the hand and forearm one week prior to the acute

experiment.



Preparation. Each animal was premedicated with

atropine (1.0 cc), and then put into a 72 liter plastic

container that had been filled with isoflurane (about 4%).

The animal was removed once it was flaccid (about 5 mins).

It was then intubated, given isoflurane anesthesia and

intravenous fluids consisting of: lactated Ringer's, sodium

bicarbonate (1 meq/kg/6hrs), mannitol (1 g/kg), and a

corticosteroid (dexamethasone, 2 mg/kg/8hrs). Isoflurane

anesthesia was maintained at a level between 1.5-2.5%

throughout all surgical manipulations. Each animal's core

temperature was monitored with an esophageal thermometer and









51

was maintained between 37 and 38 degrees C with a heating

pad (K-pad) and warmed paraffin bags. After placement in a

stereotaxic head holding device, the head was shaved, and an

incision was made along the midline of the head. The bone

was scraped clean of tissue, and a single 1.4 cm hole was

made unilaterally over SI cortex with a trephine. Rongeurs

were used to extend the hole to the midline. The dura was

dissected away with iridectomy scissors and precision

forceps to expose the underlying pia. The cortex was then

bathed in artificial cerebral spinal fluid (CSF; Merlis,

1940).



Recording. A recording chamber was mounted over the

opening with stainless steel screws and dental acrylic. It

was filled with artificial CSF and closed-off with a device

designed to hold a recording electrode and microdrive. This

setup formed a tight seal, but it allowed the electrode to

be positioned anywhere within the chamber, while keeping

track of the x-y coordinates to within 1/4 mm. The head was

then supported by a screw imbedded in the dental acrylic on

the skull, and the ear and eye bars were removed.

Electroencephalogram (EEG) electrodes were attached to two

screws that had been threaded into the skull over the

frontal and occipital cortices. The EEG was then

differentially amplified (10,000x), filtered (low-pass 40

Hz) and displayed continuously on an oscilloscope. Once the








52

surgery was complete, and the animal's head was suspended by

the screw in the acrylic cap, the anesthetic was changed to

nitrous oxide (66%) and isoflurane 0.5-1.0% (Tigwell and

Sauter, 1992). The animal was then given a dose of

Pancuronium (0.03 mg/kg/3hrs i.v.) and put on an artificial

respirator (Harvard; 20 breaths/min; 10 ml/kg body mass).

The plane of anesthesia was monitored by the EEG, and the

expired CO2 was maintained between 35 and 40 mm Hg.

Glass and Insl-x coated tungsten electrodes (impedance

= 50-200 kohms at 1000 Hz; see chapter 2 for electrode

construction) were lowered into the cortex with the

microdrive (Narishige). The electrode depth was chosen to

maximize the early negative potential (ca. 20 ms). In this

way, the recordings were always near to, but deeper than,

layer IV. Evoked potentials were differentially amplified

(10,000x), digitized (Vetter) and saved on magnetic tape

(VCR). The potentials were also filtered (3-300 Hz) and

averaged on-line (1 ms bin width; RC Electronics A-D board

and software). The averages were saved on disk in ASCII

format.



Stimulation. Electrocutaneous stimuli were delivered

to the thenar eminence and ankle of each foot. These

stimuli were similar to those described above in the Chronic

Recordings. The amplitude of the thenar stimulus was

typically 5-6 mA, whereas the ankle stimulus was 12 mA.









53

Stimulus frequencies were 1.5, 2.5, 5, 7.5, and 10 pps.



Histology. At the end of each experiment, the animal

was given an overdose of sodium pentobarbital (195 mg i.v.)

and perfused through the heart. The stumptails were

perfused with saline and 1 ml/L of heparin sulfate, and then

with 10% formalin. The rhesus monkeys were perfused first

with warmed (36 degrees C) phosphate buffer (7.4 pH) and

heparin sulfate, and then with fixative (2% paraformaldehyde

and 2.5% glutaraldehyde). This was followed by a mixture of

fixative and 10% glycerol and rinsed with 10% glycerol in

phosphate buffer. The brain and spinal cord were removed,

and the cortex was photographed. The spinal cord and cortex

were blocked and cryo-protected in 30% sucrose (or glycerol)

and 10% formalin for a minimum of 1 week. Frozen sections

were cut at 50 um, and stained with cresyl violet. In

animals with DC lesions, the extent of the lesion in the

cord was reconstructed with camera lucida drawings.



Data Analysis. Averages were compiled on-line from

100-150 stimuli, converted to ASCII files and saved on disk

for later analysis. The data were analyzed with spreadsheet

software where peak values of n20 were computed relative to

a baseline value. The baseline was taken as the maximum

amplitude between about 10 and 15 ms after the stimulus.

For each recording location, evoked potential amplitudes









54

were expressed as percent of the response to 1.5 pps.



Results

Chronic Recordings



Histology. The locations of the recording electrodes

for the three animals are shown in Figure 3-1 (arrows). The

active electrodes were either directly over or bordered the

SI cortex in all three animals. In monkey C, the active

electrodes (indicated by arrows) were located over the

posterior half of the precentral gyrus (in the motor strip).

The electrode used to record from the DC deafferented cortex

(on the left) was actually over the midline in monkey C.

However, the potentials from the two sides of the animal

were similar in shape and latency, and these potentials were

similar to those obtained in the other animals. Therefore,

it is likely that recordings from all three animals arose

from similar sources in the cortex.

The dorsal column lesions in all three animals were

complete and are shown in Figure 3-2. Monkey F received two

consecutive lesions separated by four months. The first DC

lesion (right side) was at spinal cord level T7, included

some of the grey matter in the dorsal horn and crossed the

midline in the most dorsal part of the left DC. The second

DC lesion in monkey F was between level T3 and T4 on the

left, and it included gray matter in the dorsal horn at the









55

midline. This lesion crossed the midline to include the

dorsal aspect of the right DC, and it crossed the dorsal

root entry zone to include a small portion of the DL tract.

The DC lesion in monkey S was on the right, between T8 and

T9; it crossed the midline to include the ventro-medial

portion of the left DC, and it included dorsal grey matter

up to and including the central canal. The DC lesion in

monkey C was the largest of the three animals. It was

between T7 and T8 on the right, and it included much of the

left DC, sparing a dorsal-lateral portion. In addition,

part of the right DL tract was included in this lesion.



Mechanical stimulation. A normal epidural evoked

potential recorded over SI cortex (see Figure 3-1 for

location) in response to a mechanical displacement of the

skin (0.4 mm, 10 ms, 1.5 pps) is shown in Figure 3-3. The

solid line denotes the average response (monkey S),

accumulated from 210 stimulus presentations over 5 recording

sessions (days), and the dashed lines represent plus and

minus one standard error (SE) at each time point along that

average (1 ms bin width). The first major positive peak

occurred around 20 ms after the onset of the stimulus (see

also Table 3-la). The next two major peaks in the response

were around 50 ms and 90 ms. Although these peaks did not

always occur at exactly these latencies under all stimulus

conditions in all animals, p20, n50 and p90 will be used to









56

refer to these major peaks for ease of nomenclature.

The effects of different stimulus frequencies on the

evoked potential from normal monkeys are shown in Figure 3-

4. Stimulus frequencies ranged from 1.5 to 10 pps and are

listed to the right of each trace. The control frequency

(1.5 pps) was repeated at the end of each series to monitor

any possible changes in the response over the recording

session. In this Figure, the stimuli were averaged in

sweeps of 500 ms. At 10 pps the evoked potentials from

successive stimuli interact, since each response lasted

longer than the inter-stimulus-interval (100 ms). Following

interruption of the DC, the evoked potential in response to

mechanical stimulation was attenuated considerably, even at

1.5 pps (Figure 3-5, monkey S). At 10 pps the potential was

nearly buried in the noise. Note that the amplification

scale is the same in both Figures 3-4 and 3-5. After DC

lesions, a large attenuation of responses to all frequencies

was observed in all three animals when stimulated

mechanically.

This result is shown quantitatively for the three

animals in Figure 3-6 by expressing the amplitudes of the

p20-n50 complex (top) and p90-n50 complex (bottom) in terms

of average percent of the pre-lesion amplitude at 1.5 pps.

The pre-lesion (solid line, open triangles) frequency-

response function does not drop below 50% at 10 pps for

either complex. On the other hand, the post-lesion response









57

(long dashes, open squares) to 1.5 pps is nearly 20% of the

pre-lesion response to 1.5 pps, and the post-lesion response

to 10 pps is just above the noise (solid line = average

noise, short dashes = 95% confidence interval). For both

the p20-n50 and p90-n50 complexes there was a statistically

significant effect of the lesion on response amplitude (y-

intercept) at the p<0.01 level. Each individual animal also

showed a significant amplitude shift (see Tables 3-2 and 3-

3).

It was also of interest to determine if there was a

change in the slope of the frequency-response function with

the lesion. That is, did the lesion cause a greater

frequency-dependent suppression at 10 pps relative to 1.5

pps? This is shown quantitatively in Figure 3-7 by

expressing the amplitude of both pre- and post-lesion

complexes in terms of percent amplitude of the each response

to 1.5 pps. Neither the p20-n50 nor the p90-n50 complexes

showed a significant change in slope, as a result of the

lesion, in response to mechanical stimulation. This was

also true for individual animals (Tables 3-2 and 3-3);

however, the post-lesion potentials were limited by a floor

effect, starting with considerable attenuation of responses

to the low frequency (Figure 3-6).

Not only were responses to a mechanical stimulus

significantly suppressed at stimulus frequencies between 1.5

and 10 pps, but a similar result was obtained from one









58

animal (monkey C), with stimulation at 0.1 pps in both the

pre-lesion and post-lesion conditions. The post-lesion p20-

n50 and p90-n50 complexes were suppressed to 23.4% and 18.4%

of pre-lesion amplitudes, respectively. These results

suggests that, over a 100 fold range of stimulus

frequencies, interruption of the DCs suppressed responses to

mechanical stimulation by at least 40% at all frequencies,

and by greater than 70% at low frequencies.



Electrocutaneous Stimulation. A normal evoked

potential, recorded over SI cortex (monkey S) in response to

electrocutaneous stimulation of the foot (0.2 ms, 4 mA, 1.5

pps), is shown in Figure 3-8. This potential was recorded

from the same electrode location as the potential shown in

Figure 3-3; however, it was recorded on alternate days. The

average (solid line) and SE (dashed lines) of the response

at each time point are shown for 303 stimulus presentations

collected over five separate days. The latencies of the

different peaks were approximately the same as for the

mechanical stimulation (Table 3-1b). However, in this

figure a stimulus artifact can be seen at 0 ms.

Responses to different frequencies of electrocutaneous

stimulation are shown in Figure 3-9 for the normal cortex

and Figure 3-10 for the DC deafferented cortex. In general,

the shape of the normal evoked potential did not change

substantially in response to different stimulus frequencies,









59

except for 10 pps, where successive responses interacted.

There was also a shift in the n50 minimum to an earlier

latency at frequencies between 2.5 pps and 5 pps. The

effect of a DC lesion on the responses to electrocutaneous

stimulation was to decrease the overall amplitude, though

not to the extent seen for mechanical stimulation (shown in

Figures 3-3 and 3-4). This improvement in the post-lesion

signal-to-noise ratio provided an opportunity to examine

frequency-dependent suppression in the absence of a floor

effect, in contrast to the response from the mechanical

stimulus.

Figure 3-11 shows the effect of a DC lesion on averaged

frequency-response amplitudes, for both the p20-n50 (top)

and p90-n50 (bottom) complexes. The p20-n50 complex was

reduced in amplitude by 60% or more at all frequencies post-

lesion relative to the pre-lesion amplitude at 1.5 pps

(p<0.01). This decrease in amplitude was also significant

(p<0.01) for the p20-n50 complex in each of the three

animals. The y-intercept was not significantly altered for

the p90-n50 complex; however, since the average function was

not linear, this was not a valid test. When the difference

between the pre-lesion mean amplitude (across frequency) and

post-lesion mean amplitude of the p90-n50 complex was tested

for significance (t-test), there was a reliable difference

between means (p<0.05). One animal (monkey S) that had a

relatively linear function showed a significant change in









60

the y-intercepts (p<0.01) of the functions relating

amplitude of the p90-n50 complex to frequency (see also

Tables 3-2 and 3-3).

The DC lesion led to an increased frequency-dependent

suppression of the p20-n50 response to electrocutaneous

stimulation of the foot (Figure 3-12, top). This effect was

not observed in the p90-n50 complex (Figure 3-12, bottom).

The slope of the frequency response function was

significantly (p<0.01) steeper in the post-lesion cortex

than the pre-lesion cortex for p20-n50. There was about a

20% greater reduction in amplitude at 10 pps following the

lesion, relative to the pre-lesion suppression by 10 pps.

This frequency-dependent suppression was true for two of the

three individual lesions (p<0.05; see Table 3-2).

Thus, the p20-n50 complex of the evoked responses to

electrocutaneous stimulation was significantly decreased in

amplitude by a DC lesion, and frequency-dependent

suppression was increased. This was also true for the p90-

n50 complex in amplitude but not for frequency-dependent

suppression.



Ankle stimulation. A normal evoked potential, recorded

over SI cortex (monkey C) in response to electrocutaneous

stimulation of the ankle (0.2 ms, 12 mA, 1.5 pps), is shown

in Figure 3-13. This potential was recorded from the

electrode location shown in Figure 3-1. The average (solid









61

line) and SE (dashed lines) of the response at each time

point are shown for 320 stimulus presentations collected

over five separate days. The latencies of the different

peaks were approximately the same as for mechanical

stimulation and electrocutaneous stimulation to the foot

(Table 3-ic). In this Figure, the stimulus artifact is a

small negative deflection at 0 ms.

Averaged responses to different frequencies of ankle

stimulation are shown in Figure 3-14 for normal cortex and

Figure 3-15 for the DC deafferented cortex. In the normal

cortex, p20 remained relatively constant with changes is

stimulus frequency, whereas p90 suppressed with increasing

frequency. Following the DC lesion, there was about a 40%

reduction in the amplitude of the p20-n50 complex at all

frequencies (Figure 3-16). After the lesion, the p90-n50

complex showed about a 50% reduction in amplitude at 1.5 pps

but only a 10-15% reduction in amplitude at 10 pps. Both

the p20-n50 and p90-n50 complexes showed a significant

(p<0.01) decrease in amplitude following the lesion. The

individual animals also showed this effect (see Tables 3-2

and 3-3).

The frequency-dependent suppression following the DC

lesion was similar to the pre-lesion condition. There was a

20-50% reduction at 10 pps relative to 1.5 pps for both

complexes (Figure 3-17). One of the animals (monkey S)

showed a significant difference in slope for the p20-n50









62

complex between the normal and the DC-deafferented cortex

(p<0.05), but this was not true for the average of the

animals. It should be noted that, in monkey S, the

comparison between the sides was made after the DC lesion;

consequently, there was a partial DC lesion on the control

side of this animal.

The evoked potential recorded in response to

electrocutaneous stimulation of the ankle showed that

interruption of the DC led to a change in the amplitude of

both the p20-n50 and p90-n50 complexes. However, there was

no significant change in the slope of either frequency-

response function following the DC lesion, in contrast to

the results from electrocutaneous stimulation of the thenar

eminence of the foot.



Summary of Chronic Recordings. The awake recordings

showed that under all stimulus conditions there was a

statistically significant change in the amplitude of the

evoked potential following interruption of the DC. When

electrocutaneous stimulation to the sole of the foot was

used, there was a significant change in the frequency-

dependent suppression of the early response after a DC

lesion. This result was not observed under conditions of

mechanical stimulation of the foot or electrical stimulation

of the ankle.


















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Table 3-1. Evoked potential latencies. Each block shows the peak latencies for each
component of the evoked potential in response to electrocutaneous, mechanical or ankle
stimulation before and after a DC lesion.

Monkey Stimulus Pre-les Pre-les Pre-les Pst-les Pst-les Pst-les
/Foot p20 (ms) n50 (ms) p90 (ms) p20 (ms) n50 (ms) p90 (ms)
F/R elec 21.0 48.0 96.0 23.0 48.0 93.0
F/L elec 21.0 48.0 95.0 23.0 45.0 87.0
S/R elec 19.5 55.0 83.0 23.0 56.0 94.0
Average 20.5 50.3 91.3 23.0 49.7 91.3
Std. Dev. 0.87 4.04 7.23 0.00 5.69 3.79
C/R mech 23.0 58.5 85.5 25.0 46.0 92.0
F/L mech 23.0 55.0 93.0 23.0 53.0 93.0
S/R mech 22.0 47.0 89.5 26.0 42.0 90.0
Average 22.7 53.5 89.3 24.7 47.0 91.7
Std. Dev. 0.58 5.89 3.75 1.53 5.57 1.53
S/L* ankle 17.0 33.0 88.0 -
S/R ankle 19.0 55.0 77.0
C/R ankle 19.0 55.0 84.0 19.0 47.0 87.0
Average 18.0 44.0 86.0 12.7 34.0 54.7
Std. Dev. 1.41 15.56 2.83 10.97 29.72 47.61

* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle
stimulation. All recordings were made (after a right DC lesion) on the control and deafferented
sides.
















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Figure 3-3. Averaged pre-lesion evoked potential,
recorded over SI cortex in response to mechanical
stimulation of the foot (monkey S). Solid line
represents the average of responses to 210 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.
















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Figure 3-6. Combined averages of 3 monkeys' evoked
potentials in response to mechanical stimulation,
before and after a DC lesion. Amplitudes are expressed
as percent of the pre-lesion response to 1.5 pps.
Error bars are + 1 SE. (TOP) The amplitude of the
p20-n50 complex. (BOTTOM) The amplitude of the p90-
n50 complex. Solid line along each x-axis represents
the mean amplitude of the noise, and the short dashes
represent the 95% confidence interval of that noise.









P20-N50
Mechanical stimulation


A pre-lesion
0 post-lesion


----- ----- -----: ^ -- --- -

2 4 6 8 10
Stimulus frequency (pps)


P90-N50
Mechanical stimulation


A pre-lesion
a post-lesion


10
10


100-


100-


i I I .
---------- -------- --


2 4 6 8
Stimulus frequency (pps)









Figure 3-7. Combined averages of 3 monkeys' evoked
potentials in response to mechanical stimulation,
before and after a DC lesion. Amplitudes are expressed
as percent of either the pre-lesion or post-lesion
response to 1.5 pps. (TOP) The amplitude of the p20-
n50 complex. (BOTTOM) The amplitude of the p90-n50
complex. Error bars are + 1 SE.









P20-N50
Mechanical stimulation


-1


A pre-lesion
o post-lesion


4 6
ulus frequency


P90-N50
Mechanical stimulation


A pre-lesion
0 post-lesion


' I


2
Stimulus


4 6
frequency


100-







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" 60-

0
U
40-

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2S
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100-


8
(pps)


i i


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Figure 3-8. The averaged pre-lesion evoked potential
recorded over SI cortex in response to electrocutaneous
stimulation of the foot (monkey S). Solid line
represents average of responses to 303 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.





81











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40-
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Figure 3-11. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
before and after a DC lesion (3 lesions). Amplitudes
are expressed as percent of the pre-lesion response to
1.5 pps. Error bars are + 1 SE. (TOP) The amplitude of
the p20-n50 complex. (BOTTOM) The amplitude of the
p90-n50 complex. Solid line along each x-axis
represents the mean amplitude of the noise, and the
short dashes represent the 95% confidence interval of
that noise.










P20-N50
electrocutaneous stimulation
A pre-lesion
7T post-lesion


0-



- ---- --.



0- I I

0 2 4 6 8 10
Stimulus frequency (pps)


P90-N50
electrocutaneous stimulation
A pre-lesion
0 post-lesion


\ ---


100-


100-


80



60-



40-



20-



0-


2 4 6 8
Stimulus frequency (pps)


I








Figure 3-12. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
before and after a DC lesion (3 lesions). Amplitudes
are expressed as percent of either the pre-lesion or
post-lesion response to 1.5 pps. Error bars are + 1 SE.
(TOP) The amplitude of the p20-n50 complex. (BOTTOM)
The amplitude of the p90-n50 complex. Lines drawn
through data points are least-squares-fit.










P20-N50


mulation
A pre-lesion
3 post-lesion


N
N N


I 6I
2 4 6
Stimulus frequency


8
(pps)


P90-N50
electrocutaneous stimula


10





tion
A pre-lesion
a post-lesion


2 4S 6 8
Stimulus frequency (pps)


100-

0-
in
g_ 80-
uin


100-


O-
S80

LO


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0

U
u






E


10


i









Figure 3-13. The averaged pre-lesion evoked potential
recorded over SI cortex in response to electrocutaneous
stimulation of the ankle (monkey C). Solid line
represents average of responses to 320 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.

















Ankle stimulation


p90


p20


n50


-30 -
-100


1
-50


I I I
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Full Text
Figure 3-9. Pre-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 10 pps (right of each trace).
From 303 to 320 averages were accumulated from recordings on 5 days.


167
Mendenhall, W., Scheaffer, R.L., Wackerly, D.D. (1986)
Mathematical statistics with applications. Third
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Merzenich, M.M., Nelson, R.J., Stryker, M.P., Cynader, M.S.,
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cortical map changes following digit amputation in
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Nathan, P.W., Smith, M.C., Cook, A.W. (1986) Sensory
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Nijensohn, D.E., Kerr, F.W.L. (1975) The ascending
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cord in primate. J. Comp. Neurol. 161:459-470.
Pillay, N. (1984) Visual, brainstem auditory and
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17
months prior to the acute experiment, one animal (monkey E)
had a surgical interruption of the dorsal column on the
right side between Til and T12 (see Histology). This
procedure was conducted under sterile surgical conditions by
Dr. C. J. Vierck, Jr. (see Chapter 3 Methods for details).
Preparation. Each animal was premedicated with
intramuscular (i.m.) ketamine HCL (100 mg) and atropine
sulfate (.54 mg), given intravenous (i.v.) fluids (lactated
Ringers) and then intubated. Isoflurane anesthesia was
passed to the animal and maintained at a level of 1.5-2.5%
throughout the remainder of the experiment. Each animal's
core temperature was monitored with an esophageal
thermometer and was maintained between 37 and 38 degrees C
with a heating pad (K-pad) and warmed paraffin bags. The
back of the animal was then shaved and a rostral-caudal
incision was made over the low thoracic vertebrae. The
muscle and fascia were scraped away from the dorsum of 4 or
5 vertebrae, and 2 or 3 of the dorsal laminae were removed
with rongeurs. The underlying fat and connective tissue
were dissected away, exposing the dura mater. A rostral-
caudal slit was made in the dura, and it was reflected to
expose the pia. The cord was then bathed in warm (37
degrees C) mineral oil. The remaining two spinous processes
at the rostral and caudal extent of the exposure were then
clamped and suspended by a stereotaxic frame.
Stimulation and recording. Each foot was stimulated


56
refer to these major peaks for ease of nomenclature.
The effects of different stimulus frequencies on the
evoked potential from normal monkeys are shown in Figure 3-
4. Stimulus frequencies ranged from 1.5 to 10 pps and are
listed to the right of each trace. The control frequency
(1.5 pps) was repeated at the end of each series to monitor
any possible changes in the response over the recording
session. In this Figure, the stimuli were averaged in
sweeps of 500 ms. At 10 pps the evoked potentials from
successive stimuli interact, since each response lasted
longer than the inter-stimulus-interval (100 ms). Following
interruption of the DC, the evoked potential in response to
mechanical stimulation was attenuated considerably, even at
1.5 pps (Figure 3-5, monkey S). At 10 pps the potential was
nearly buried in the noise. Note that the amplification
scale is the same in both Figures 3-4 and 3-5. After DC
lesions, a large attenuation of responses to all frequencies
was observed in all three animals when stimulated
mechanically.
This result is shown quantitatively for the three
animals in Figure 3-6 by expressing the amplitudes of the
p20-n50 complex (top) and p90-n50 complex (bottom) in terms
of average percents of the pre-lesion amplitude at 1.5 pps.
The pre-lesion (solid line, open triangles) frequency-
response function does not drop below 50% at 10 pps for
either complex. On the other hand, the post-lesion response


44
animal's ability to perform the task.
The above reasoning led to the experiments below. The
idea was to determine changes in the cortical evoked
potential following a DC lesion. In this way, the neural
mechanisms underlying the behavioral deficit might be
ascertained.
Methods
Chronic Recordings
Subjects and Training. The subjects were three female
Macaca arctoides (stumptailed macaques) that weighed between
8.6 and 11.3 kg. These animals were not used in the acute
spinal cord experiments. The animals were housed in an
outdoor communal enclosure to maximize their health and
psychological well being. They were tested five or six days
a week. Each day the animals were led into the laboratory
on a leash and seated comfortably in a plexigls primate
chair. They were gradually trained to tolerate gentle
restraint of their wrists and ankles by leather straps. In
the chair, apple sauce was dispensed through a tube in
response to the animal pressing a bar. After 10-15 min in
the chair, each animal was returned to its home "run" for
the normal diet of Purina monkey chow, fruit and water (ad
libitum).


EFFECTS OF A DORSAL COLUMN LESION ON SOMATOSENSORY EVOKED
POTENTIALS IN PRIMATES
By
JAMES C. MAKOUS
A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN
PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF DOCTOR OF PHILOSOPHY
UNIVERSITY OF FLORIDA
1993


120
occur in the thalamus (Garraghty and Kass, 1991; Rausell et
al., 1992) or cortex (Merzenich et al., 1984; Pons et al.,
1991) .
This line of reasoning was the impetus for the
experiments below. If the cortical evoked potential changed
over weeks after a DC lesion, this would provide evidence
for changes in connectivity of the spared pathways. An
alteration in the early peak would suggest a subcortical
change because that peak arises from input to layer IV and
its associated depolarization. If a change were restricted
to one of the later peaks, this would reflect a cortical
modification following the lesion, since those peaks arise
from a spread of intracortical activity. No change in the
response could result from the evoked potential measure
being insensitive to changes that occur, but it would also
indicate that there was not a substantial reorganization
taking place within the spared pathways.
METHODS
The methods for these experiments were similar to those
outlined in Chapter 3; therefore, they will only be briefly
outlined here. Any differences in methodology will be
noted.


2
in response to light tactile stimuli and with respect to
recovery from these deficits.
Behavior
Given the ambiguities in the clinical findings,
investigators have attempted to quantify sensory capacities
in animal models, where a lesion can be isolated to an
individual pathway and confirmed histologically. Vierck
(1977), using Von Frey hair stimulation, showed that there
was no threshold shift on the sole of the foot following a
mid-thoracic DC lesion. For a variety of other tasks,
considerable recovery of function has been observed
following a DC lesion. DeVito and colleagues (1964) found
that monkeys had only a transient deficit in weight
discrimination, and Vierck (1966) found no permanent effect
on limb position sense. Levitt and Schwartzman (1966) showed
a transient deficit in two-point discrimination;
discriminations of size and location of tactile stimuli also
recover (Vierck, 1973; Vierck et al., 1983, 1988). For many
years there was no firm evidence of any permanent sensory
deficit following interruption of the DCs. In fact, Wall
(1970, p. 518) was so bold as to say that the DCs are only
'involved in controlling the analysis of messages arriving
over the other somatosensory pathways.'
More recently, tasks that require some degree of
temporal resolution have shown long lasting sensory deficits


Figure 2-6. Responses obtained from each subdivision of the spinal
cord, averaged across animals. Amplitudes are expressed as a percentage
of the response to 1.5 pps. Error bars represent + 1 SE. The SEs for
the AL, pl4 response were omitted for clarity and ranged from about 5%
to about 20% depending on the stimulus frequency. The points shown in
the lower left of the Figure represent responses to stimulation of the
control foot for each subdivision.


Figure 4-11. Time course (days) of changes in the
evoked potential amplitude (p90) averaged across
animals. The data from three monkeys, shown in Figure
4-7, were averaged into 10 day blocks of time. Each
block contained anywhere from 2 to 14 values with a
median of 6. Error bars are + 1 SE.


Figure 2-3. Compound action potentials recorded from
the DC of monkey D. (TOP) The responses to different
frequencies of ipsilateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the contralateral (control) foot at 1.5
pps expressed as percentage of the ipsilateral response
at 1.5 pps.


Figure 3-21. Evoked potentials recorded from normal
cortex during acute experiments in response to
electrocutaneous stimulation. Solid lines represent
the response to 1.5 pps, and the dashed lines represent
the response to 10 pps. (TOP) Responses recorded near
the CS in response to stimulation of the foot.
(BOTTOM) Response recorded near the 1,2 border in
response to ankle stimulation. (a and b represent the
time windows over which the peak-to-peak amplitude was
computed.


20
to contralateral stimulation. These locations often
produced an ipsilateral response that was less than 40% the
amplitude of the contralateral response.
After an electrode was placed in one of the tracts by
one of the above functional definitions, a frequency series
was conducted. In the case of the DC and DL tracts the
ipsilateral foot was stimulated, whereas the contralateral
foot was stimulated for the AL recordings. These three
stimulus conditions will be referred to as stimulation of
the experimental foot. whereas stimulation of the non-
experimental foot will be referred to as stimulation of the
control foot. Each frequency series consisted of 100-150
sweeps by the averaging software over a sweep duration of 75
ms. Thus, for the higher frequencies, the animal received
more stimuli (i.e. at 1.5 Hz there was 1 stimulus/sweep and
at 50 Hz there were 3 stimuli/sweep). The stimulus sequence
was typically as follows: experimental foot (at 1.5, 2.5,
5.0, 7.5, 10, 25, 50 and then 1.5 Hz), control foot (1.5
Hz), and experimental foot (1.5 Hz).
Data analysis
The data were analyzed off-line. "Raw" evoked
potential records were read off magnetic tape, band-pass
filtered (3-300 Hz), digitized (300 us bin width) and
averaged by commercially available software (RC
electronics). The 75 ms long averages were converted into


30
Spinal cord recordings
dorsal column
time (ms)


22
glycerol) solution for a minimum of 1 week. Transverse
sections were cut on a freezing microtome at 50 urn, mounted
on slides and let dry for a minimum of 1 day. They were
then stained (cresyl violet) and cover-slipped (Permount).
The extent of the DC lesion was drawn, and the electrode
tracks were reconstructed.
Results
Histology
The locations of the recording electrodes were verified
histologically in all recordings. Each of the recording
sites for each animal is shown in Figure 2-1. The DC
recordings were typically near the midline and in the
ventral half of the DCs. In one animal (monkey K), the
recording site bordered the grey matter. The DL recordings
were usually confined to the DL quadrant but occasionally
bordered the ventral quadrant of the cord. The AL
recordings were usually ventral to, but occasionally
bordered, the DL quadrant. During the AL recordings it was
often difficult to eliminate the response from the control
foot, especially at 11 ms.
The DC lesion in monkey E was between Til and T12 and
is shown in Figure 2-2. There was complete interruption of
the right DC at this level. There was very little
involvement of the left DC or the grey matter and no
encroachment into the right DL.


55
midline. This lesion crossed the midline to include the
dorsal aspect of the right DC, and it crossed the dorsal
root entry zone to include a small portion of the DL tract.
The DC lesion in monkey S was on the right, between T8 and
T9; it crossed the midline to include the ventro-medial
portion of the left DC, and it included dorsal grey matter
up to and including the central canal. The DC lesion in
monkey C was the largest of the three animals. It was
between T7 and T8 on the right, and it included much of the
left DC, sparing a dorsal-lateral portion. In addition,
part of the right DL tract was included in this lesion.
Mechanical stimulation. A normal epidural evoked
potential recorded over SI cortex (see Figure 3-1 for
location) in response to a mechanical displacement of the
skin (0.4 mm, 10 ms, 1.5 pps) is shown in Figure 3-3. The
solid line denotes the average response (monkey S),
accumulated from 210 stimulus presentations over 5 recording
sessions (days), and the dashed lines represent plus and
minus one standard error (SE) at each time point along that
average (1 ms bin width). The first major positive peak
occurred around 20 ms after the onset of the stimulus (see
also Table 3-la). The next two major peaks in the response
were around 50 ms and 90 ms. Although these peaks did not
always occur at exactly these latencies under all stimulus
conditions in all animals, p20, n50 and p90 will be used to


18
electrocutaneously at the tibial nerve, posterior to the
medial malleolus at a current sufficient to elicit a small
twitch of the first toe (ca. 5 mA). The duration of each
pulse was 0.2 ms, and the frequency of stimulation was
varied systematically from 1.5 pulses per second (pps) to 50
pps. Stimulating electrodes consisted of silver/lead solder
molded into a small bead 4 mm in diameter. The anode and
cathode were separated by 2 cm (cathode proximal),
lubricated with sergi-lube and held in place with adhesive
pads and tape. The animal was grounded with a ring
electrode placed around each calf proximal to the
stimulating electrode.
Compound action potentials were recorded from the white
matter tracts of the spinal cord by lowering tungsten
electrodes into the cord with a X-Y-Z micro-positioner.
Tungsten electrodes were made by immersing a tungsten rod
(0.007 in. diameter) into a bath of saturated sodium nitrite
and passing an AC voltage (ca. 6 volts) between the tungsten
and a carbon rod, also in the bath. The tungsten was then
slowly removed from the bath, and, in this way, a blunt
point was etched onto the end of the electrode. The
sharpened end of the tungsten was then passed through the
back end of a glass micro-pipette. The tip of the pipette
was broken to allow about 1 cm of exposed tungsten. The
tungsten was held in place by dental wax, and the entire
exposed tip of the electrode was dipped in Insl-x


Amplitude ($ control: prelesion) Amplitude (5? control: prelesion)
77
P20-N50
40-
0 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
100-1
80-
60-
40-
P90-N50
Stimulus frequency (pps)
lesion
-lesion
lesion
-lesion


58
animal (monkey C), with stimulation at 0.1 pps in both the
pre-lesion and post-lesion conditions. The post-lesion p20-
n50 and p90-n50 complexes were suppressed to 23.4% and 18.4%
of pre-lesion amplitudes, respectively. These results
suggests that, over a 100 fold range of stimulus
frequencies, interruption of the DCs suppressed responses to
mechanical stimulation by at least 40% at all frequencies,
and by greater than 70% at low frequencies.
Electrocutaneous Stimulation. A normal evoked
potential, recorded over SI cortex (monkey S) in response to
electrocutaneous stimulation of the foot (0.2 ms, 4 mA, 1.5
pps), is shown in Figure 3-8. This potential was recorded
from the same electrode location as the potential shown in
Figure 3-3; however, it was recorded on alternate days. The
average (solid line) and SE (dashed lines) of the response
at each time point are shown for 303 stimulus presentations
collected over five separate days. The latencies of the
different peaks were approximately the same as for the
mechanical stimulation (Table 3-lb). However, in this
figure a stimulus artifact can be seen at 0 ms.
Responses to different frequencies of electrocutaneous
stimulation are shown in Figure 3-9 for the normal cortex
and Figure 3-10 for the DC deafferented cortex. In general,
the shape of the normal evoked potential did not change
substantially in response to different stimulus frequencies,


116
amplitude. It is possible that the effects of Nembutal
anesthesia attenuated the effects of the lesion. Cusick et
al. ( 1979) on the other hand, found about a 75% reduction in
amplitude of the evoked response to electrocutaneous
stimulation after a chronic DC lesion, while under ketamine
anesthesia. Once again, the anesthetic may have affected
the recordings, but given the difference between the
approaches, this is in reasonable agreement with the current
findings.
Acute Recordings
The recordings from the anesthetized cortex showed that
there was an increased variability in the n20 response to
electrocutaneous stimulation of the foot and ankle. It was
difficult to quantify later peaks of the evoked potentials,
because they varied with recording location in both relative
amplitude and latency. Thus, only the n20 potential was
examined.
The increased variability following a DC lesion could
suggest a variety of mechanisms. It is possible that the
increased variability was merely a reflection of the fact
that the potential is small and therefore closer to the
noise. It is also possible that the noise was greater in
the DC-deafferented cortex, although none of the awake
recordings showed this result. Perhaps the anesthesia has a
greater affect on the deafferented cortex than on the normal


Figure 4-3. Time course (days) changes in of the
evoked potential amplitude following a the second DC
lesion after a long term (> 150 days) implant (monkey
F). Recordings made from both sides of the cortex are
shown. Solid lines are from a least-squares-fit to the
data points.


48
9 mm diameter probe, mounted on the end of the vibrator,
passed up through a linear voltage displacement transducer
(LVDT; Schaevitz) and then through a 1.9 cm hole drilled in
a plexiglass foot rest. The monkey's foot was held in place
by a polyform cast, such that the thenar eminence of the
foot was directly over the 1.9 cm hole. The probe was
advanced to make a 1-2 mm indentation in the skin. The
stimulus amplitude was calibrated to 0.4 mm, monitored
(LVDT) throughout each session on an oscilloscope, and saved
on magnetic tape.
Data analysis. All data were analyzed off-line. The
"raw" evoked potential records were read off tape, low-pass
filtered (100 Hz), and digitized (1000 Hz, 1 ms bin width)
by commercially available software and an A-D board (RC
Electronics). The digitized records were converted into
ASCII files for further analysis by software written in 'C
(by the author).
The averaged evoked potentials were constructed first
by discarding any traces that fell outside of a user
specified amplitude window (typically + 300 uV). This was
intended to reject evoked potentials that contained movement
artifact. The remaining traces from an individual session
were then averaged, and the standard deviation (SD) was
computed for each time point (bin) in the average. Averaged
data from individual days were combined into averages across


Figure 3-6. Combined averages of 3 monkeys' evoked
potentials in response to mechanical stimulation,
before and after a DC lesion. Amplitudes are expressed
as percent of the pre-lesion response to 1.5 pps.
Error bars are + 1 SE. (TOP) The amplitude of the
p20-n50 complex. (BOTTOM) The amplitude of the p90-
n50 complex. Solid line along each x-axis represents
the mean amplitude of the noise, and the short dashes
represent the 95% confidence interval of that noise.


p90 amplitude (uV)
136
1 I I I I 1 1 1 1 1 1
0 10 20 30 40 50 60 70 80 90 100
days post-lesion
-10-


Amplitude
Ankle stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
10 pps
1.5 pps
VO
U1


134
Monkey C
mechanical stimulus


113
change in the slope of the frequency-response function to
electrocutaneous stimulation of the foot. This increase in
frequency-dependent suppression was not observed for any
other stimulus condition. There also was an increased
variability in the amplitude of the n20 potential, in
anesthetized animals, following the DC lesion.
Chronic Recordings
The results from the awake recordings showed that there
was a large (40-80%) decrease in the amplitude of all
components of the evoked potential following a DC lesion.
This suggests that the DC in a normal animal contributes
significantly to the perception and detection of tactile
(non-noxious) stimuli. Indeed, the decrease in amplitude
following the lesion was most dramatic in the case of
mechanical stimulation; thus, the information about a
natural stimulus may be carried predominantly by the DCs.
It is likely that following such a lesion there would
be a shift in threshold for detection of a mechanical
stimulus. Although this was not found by Vierck (1977) with
von Frey stimulation, there is preliminary evidence from one
animal that a threshold shift of about 10-15 dB exists
following DC lesion for a mechanical stimulus that is in
constant contact with the skin (unpublished observations,
Friedman and Vierck). When a stimulus probe is in constant
contact with the skin, there is inevitably a form of


50
Then, the mean and variances of the estimates of the slope
and y-intercept were used to compute the test statistic 't.'
This was a conservative test.
Acute Recordings
Animals. Acute recordings from SI cortex were obtained
from three female stumptailed macaques, two of which were
used in the awake experiments above, and three female rhesus
monkeys (Macaca mulatta). The rhesus monkeys were
previously used in behavioral experiments in vision, and had
received horseradish peroxidase injections in small muscles
of the hand and forearm one week prior to the acute
experiment.
Preparation. Each animal was premedicated with
atropine (1.0 cc), and then put into a 72 liter plastic
container that had been filled with isoflurane (about 4%).
The animal was removed once it was flaccid (about 5 mins).
It was then intubated, given isoflurane anesthesia and
intravenous fluids consisting of: lactated Ringer's, sodium
bicarbonate (1 meq/kg/6hrs), mannitol (1 g/kg), and a
corticosteroid (dexamethasone, 2 mg/kg/8hrs). Isoflurane
anesthesia was maintained at a level between 1.5-2.5%
throughout all surgical manipulations. Each animal's core
temperature was monitored with an esophageal thermometer and


21
ASCII files and saved on disk. ASCII files were imported
into a spreadsheet, where latencies and amplitudes could be
computed. Latency was computed from the peak of the
stimulus artifact to the peak of each distinct waveform.
The peak amplitude of the potential was computed by taking
the difference between the amplitude 6 ms after the stimulus
artifact and the amplitude at the mean latency of the peak.
The response amplitudes at each frequency were expressed as
a percentage of the amplitude of the response to stimulation
of the experimental foot at 1.5 Hz (referred to as the
standard amplitude).
Histology
At the end of each experiment the animals were given an
overdose of pentobarbital (195 mg i.v.). They were then
perfused through the heart, first with warm (37 degrees C)
phosphate buffer (7.4 pH) and heparin sulfate (1 units/L),
then with fixative (2.5% glutaraldehyde and 2.0%
paraformaldehyde). This was followed by a mixture of
fixative and 10% glycerol and then rinsed with 10% glycerol
in phosphate buffer. The spinal cord was removed from C2
down to LI; the dorsal roots were counted, and the cord was
blocked 2 levels rostral and caudal to the recording
exposure. In the animal with the DC lesion, the cord was
blocked rostral and caudal to the lesion as well. The cord
was cryo-protected in a 10% formalin and 30% sucrose (or


45
Surgery. Following chair training, epidural recording
electrodes were implanted over primary somatosensory cortex
(SI). This was done under sterile conditions at the
University of Florida animal surgery facility. The animals
were premedicated with ketamine HCL (100 mg) and atropine
sulfate (0.54 mg) before intubation; then Halothane
anesthesia was administered and maintained at 1.5-2.0%.
During the implantation, the skull was exposed, the
bone was cleared of muscle and fascia, and 10 surgical
grade, stainless steel bone screws were implanted. Five
screws were placed over each SI foot representation, in 3-4
mm increments along (3 mm lateral to) the midline (see
Figure 3-1). The stereotaxic coordinates were chosen so as
to cover and flank the foot representation on each side.
Two or four reference electrodes were also implanted over
each frontal lobe. A teflon coated platinum-iridium wire
(Medwire) was passed from the head of each screw to a
miniature D-25 connector that was encased in dental acrylic,
along with the implanted screws. The skin flaps were closed
to cover the skull not covered by acrylic. The animals were
given antibiotics (Dualpen, i.m.) for 1 week following the
surgery and Torbutrol (0.5mg/6hrs) for pain.
Another surgery was performed after normal (pre-lesion)
evoked potential recordings were collected from each animal
(typically for 2 months post-implant). During this surgery,
a unilateral fasciculus gracilis lesion was made by Dr. C.J.


25
Monkey D


Figure 2-1. Electrode recording locations from the
spinal cord white matter of three monkeys. All
recording sites are drawn on a standard mid-thoracic
(T8) section. Black ovals represent approximate
recording locations, while dashed lines connect
recordings sites within one electrode penetration.
Often, two frequency series were recorded at the
electrode location. Abbreviations as in text.


Amplitude
electrocutaneous stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
10 pps
1.5 pps
00


114
repetitive stimulation that results from small movements of
the foot relative to the probe. Because repetitive tactile
stimulation reduces the amplitude of SI cortical responses,
thresholds for detection should be elevated relative to
testing with infrequent stimulation by von Frey hairs. Such
an effect would be particularly pronounced for DC-
deaf ferented cortex, where responses to repetitive
stimulation are imbedded in background noise.
A change in the slope of the frequency-response
functions following a DC lesion was evident in the case of
the electrocutaneous stimulation of the foot. This is
physiological evidence that the DCs play a role in the
coding of stimulus frequencies between 1.5 and 10 pps. It
is possible that a slope change might have been detected in
the presence of the mechanical stimulus following the DC
lesion had the stimulus been large enough to drive the
response out of the noise.
There also was a slope change in the frequency-response
function to ankle stimulation in one of the two animals for
the p20-n50 complex on the DC deafferented side relative to
the control side. However, there were no pre-lesion data
from the ankle stimulation of this animal, and averaged
results from 2 animals showed no significant change in the
slope of the frequency-response function following the
lesion. This result suggests that frequency-dependent
suppression in exaggerated in animals with lesions for


57
(long dashes, open squares) to 1.5 pps is nearly 20% of the
pre-lesion response to 1.5 pps, and the post-lesion response
to 10 pps is just above the noise (solid line = average
noise, short dashes = 95% confidence interval). For both
the p20-n50 and p90-n50 complexes there was a statistically
significant effect of the lesion on response amplitude (y-
intercept) at the p<0.01 level. Each individual animal also
showed a significant amplitude shift (see Tables 3-2 and 3-
3).
It was also of interest to determine if there was a
change in the slope of the frequency-response function with
the lesion. That is, did the lesion cause a greater
frequency-dependent suppression at 10 pps relative to 1.5
pps? This is shown quantitatively in Figure 3-7 by
expressing the amplitude of both pre- and post-lesion
complexes in terms of percent amplitude of the each response
to 1.5 pps. Neither the p20-n50 nor the p90-n50 complexes
showed a significant change in slope, as a result of the
lesion, in response to mechanical stimulation. This was
also true for individual animals (Tables 3-2 and 3-3);
however, the post-lesion potentials were limited by a floor
effect, starting with considerable attenuation of responses
to the low frequency (Figure 3-6).
Not only were responses to a mechanical stimulus
significantly suppressed at stimulus frequencies between 1.5
and 10 pps, but a similar result was obtained from one


Figure 3-19. Approximate locations of all electrode
penetrations in the cortex. Penetrations are drawn on a
representative sagittal section of cortex taken about 2
mm from the midline. (TOP) Sixty-three penetrations
are shown in normal cortex. (BOTTOM) Fifty-four
penetrations are shown in DC-deafferented cortex. (A =
anterior; P = posterior; CS = central sulcus; 1,2 =
approximate location of border between Brodmann's areas
1 and 2.; 3,1 = approximate location of border between
Brodmann's areas 3 and 1)


160
whereas responses from the DL column were about 80% of the
DC response. If the average suppression relative to the DC
response is computed/ there was an overall 20% reduction in
the amplitude at 10 pps relative to the DC. If the simple
assumption is made that activity in the afferent pathways is
linearly summed at the cortex, then the result of this
computation is in agreement with the 20% increase in
frequency-dependent suppression that was observed in the
cortex following the DC lesion (see Figure 3-12).
Along a similar line of reasoning, if the amplitude of
the cortical evoked potential is proportional to the amount
of input to the cortex, then the cortical recordings from
animals with DC lesions are in accord with behavioral
deficits in frequency and duration discriminations. The
amplitude of the cortical response was reduced to 20-40% of
pre-lesion control responses to 1.5 pps, and the reduced
capacity to follow repetitive stimulation pushed the
response amplitude into the baseline noise at 10 pps. Since
the response to 10 pps was closest to the noise before the
lesion, it would follow that it would be most susceptible to
engulfment by the noise after the lesion.
Following a DC lesion, a substantial stimulus of 0.4 mm
was not sufficient to drive the cortical response above the
noise floor with stimulation at 10 pps. This suggests that
the DC is an important pathway for light mechanical
stimulation, which is supported by the unit findings


ACKNOWLEDGMENTS
I would like to thank my advisor, Charles Vierck, for
taking me into his laboratory at such a late stage in my
graduate education and for his patience and support of my
sometimes unorthodox ideas and experiments. I also thank
the members of my ever-changing committee, David Green,
Bruce Hunter, Richard Johnson, Christiana Leonard, Louis
Ritz and Barry Whitsel, for their critical evaluation and
support of my research. I thank William Luttge for his many
hours spent in making this a better department, John
Middlebrooks for his support during the early stages of my
training and the Center for Neurobiological Sciences for
financial support.
I would also like to thank Jean Kaufman for teaching me
to handle and care for monkeys; Anwarul Azam for keeping the
computers on-line; Carol Martin-Elkins for teaching me basic
histology. I thank Laura Kasper, James Murphy, Anita Puente
and Karl Vierck for technical expertise. I also thank
Robert Friedman, Diana Glendinning and Douglas Swanson for
their support, advice and camaraderie during all the stages
of my education. I am especially indebted to Robert
Friedman for his generosity in sharing his time, knowledge,
ii


10
found, in recordings from fibers at cervical levels, that
fibers in the FC innervated both cutaneous and deep
structures, whereas the fibers in the FG were predominantly
cutaneous. This is in contrast to recordings made more
caudally, where the fiber types were similar for both the FC
and the FG. This suggests that there is sorting of fibers
from the FG as it ascends the spinal cord, resulting in a
projection of proprioceptive afferents to the dorsal horn
and then the DL tract (Dreyer et al., 1974). Therefore, it
is possible that a lesion of the FG would produce behavioral
effects that differ from those produced by a lesion of the
FC.
Plasticity
A number of recent findings suggest there is some
degree of plasticity in the adult nervous system (see Wall,
1988 for review). For example, the results of Merzenich et
al. (1984) have shown in recordings from anesthetized
monkeys that the cortical representation of the fingers
adjacent to an amputated finger included the region of
cortex formerly dominated by input from the missing finger.
These changes in the borders of the cortical representation
were on the order of 1-2 mm and appear to represent an
unmasking of inputs that are normally suppressed by the
anesthesia. More recently, Pons et al. (1991) found that
long term (> 12 yrs) dorsal rhizotomy (C2-T4; C = cervical;


CHAPTER 4
PHYSIOLOGICAL CHANGES DURING RECOVERY FROM
A DORSAL COLUMN LESION
Following a DC lesion, a number of behavioral tasks
show significant improvement from an initial deficit that
eventually return to pre-lesion levels of performance. For
example, two-point discrimination (Levitt and Schwartzman,
1966), weight discrimination (DeVito et al., 1964), proximal
limb movements (Vierck, 1978a) and tactile size
discrimination (Vierck, 1973) recover from the lesion to
the DCs. This recovery can take anywhere from 1 to 6
months.
One problem with these findings is that it is not clear
whether the recovery resulted from neural plasticity or from
the animal learning to attend to different sensory cues.
For example, it is possible that the animals learned to
attend to the information normally carried in the pathways
spared by the lesion. On the other hand, it is also
possible that there is a change in the neural connectivity
of the spared pathways to compensate for the loss of the
DCs. These changes could take place in the dorsal horn
and/or dorsal column nuclei, where the primary afferents
synapse (Goldberger and Murray, 1982). Changes could also
119


34
Spinal cord recordings
antero-lateral
20 \
- I
tiir| i iii|iiii p
5 10 15
time (ms)
control
' foot
~l
20
0


p90 amplitude (uV)
130
-1 oH 1 1 1 1 1 1 1 1 1
0 10 20 30 40 50 60 70 80 90 100
days postlesion


UNIVERSITY OF FLORIDA
3 1262 08557 0371


152
a decrease in calcium binding proteins specific for the
lemniscal afferent pathway, whereas there was an increase in
calcium binding proteins specific for spinal thalamic tract
neurons. There was also a down regulation of GABA (type A)
receptors (same monkeys as Pons et al., 1991). Indeed,
these changes were found in an area of high convergence: the
ventro-basal complex of the thalamus (Berkley, 1980; 1983).
Thus, these changes would affect responses at the cortical
level.
Garraghty and Kass (1991) also found changes in the
thalamus following median and ulnar nerve transection and
ligation, which completely deafferents a region of rostral
somatosensory pathways. Receptive fields on hairy skin were
observed in a region of the thalamus that normally has
receptive fields only on the glabrous skin of the hand.
Thus, there was a change, again in the ventro-basal complex
of the thalamus, in physiological response properties after
a 2-5 month recovery from nerve transection.
There also have been reports of sprouting in the dorsal
horn and dorsal column nuclei following dorsal rhizotomy in
cats (Goldberger and Murray, 1982). However, these changes
were limited to regions of the cord that normally receive
projections from a root spared of the rhizotomy and to
regions devoid of a detailed somatotopic map. Thus, it is
unlikely that sprouting at this level would lead to changes
in the somatotopic map in the cortex, though they might


100
Acute Recordings
Two stimulus configurations were used to record evoked
potentials from anesthetized animals; electrocutaneous
stimulation was delivered to the thenar eminence of the foot
and to the ankle. Electrode penetrations were made at about
1 mm increments, typically covering more than 1/2 square cm
of SI cortex.
Histology. Figure 3-18 shows a sagittal section taken
from a macaque cortex 7 mm from the midline (Winters et al.,
1969). The central sulcus (CS), post-central sulcus (PCS),
intra-parietal sulcus (IPS) and cingulate sulcus (CgS) can
be clearly seen in this figure. Two of these landmarks
(central sulcus and cingulate sulcus) are also on a
representative section (Figure 3-19), which was taken about
2 mm from the midline. Figure 3-19 shows the distribution
of electrode penetrations in the normal animals (top) and
the DC deafferented animals (bottom). It shows that ninety-
eight percent of the electrode penetrations were located in
the deep layers or underlying white matter of Brodmann's
areas 3,1 and 2. Two penetrations were localized to the
most caudal aspect of area 4, along the midline.
The histological reconstructions of the DC lesions for
the acute experiments is shown in Figure 3-2 for monkey F
and C and for monkey R6 in Figure 3-20. See the Histology
section under Chronic Recordings for discussion of the


control: 1.5
1 10
Stimulus frequency (pps)


p90 amplitude (uV)
144
50 n
40-
30-
20-
10
10-
Combined response (normalized)
control side
A
a x
a x a
x A a
A A
A x
A
X
~ A
0 ~¡0 20 30 40 50 60 70 80 90~
days postlesion
A monkey F
x monkey S
Too


40
peak was derived from a third group of fibers in the AL,
given its different latency and unique frequency
sensitivity.
One animal (monkey K) showed no appreciable pll
response in the AL tract. It is not clear why this
occurred, since the recording electrode in this animal did
not appear to be in a substantially different location than
the other two animals. It is possible that the high
electrode impedance (100 kohms) used in this animal drew
from a smaller population of fibers than the electrodes used
in the other two animals (15 and 65 kohms).
Frequency Response
The DC response showed less suppression than the other
two tracts at all frequencies above 10 pps. This result was
not unexpected since the DL and AL tracts do not contain
primary afferent fibers. Because each synaptic delay tends
to decrease the reliability of high frequency transmission,
the DC should be better equipped to carry high frequency
information up the cord. Conversely, one could argue that
the AL and DL tracts do carry high frequency information,
but it is lost in the averaged response, owing to a variable
latency of individual responses. If this were the case, one
would expect to see not only a decrease in the amplitude of
the response at high frequencies, but also a broadening of
the peak at high frequencies. This was not observed in
either the DL or the AL tracts.


BIOGRAPHICAL SKETCH
James Carl Makous was born to Marilyn and Walter on 9
August 1963, in Mt. Kisco, New York. After growing up in
Seattle and graduating from Ingraham High School in 1981, he
moved back east to New York to pursue his interest in
physics at the University of Rochester. After taking a few
courses in biopsychology he changed his major to
neuroscience. He then entered the laboratory of William E.
O'Neill and undertook experiments on the neurophysiology of
bat echolocation. After graduating in 1985 with a B.S. in
neuroscience, he worked in Robert Doty's laboratory under
the watchful eye of Sandy Bolanowski and participated in
experiments in visual psychophysics and physiology. He then
returned to his first love, the auditory system, when he was
accepted into the laboratory of John Middlebrooks at the
University of Florida. There he studied the neural basis of
sound localization. After 3 years, he transferred into the
laboratory of Charles Vierck where he began to study
temporal coding in the somatosensory system. While working
on his doctorate, he was happily married to Elizabeth Ann
Scott. He is now planning to return again to New York where
he will pursue his interests in somesthetic temporal coding
at Syracuse University.
171


163
that the DC-lemniscal system exerts over the projection
cells of the thalamus leaves these cells to the oscillatory
influences of the reticular nucleus. This could in turn
lead to variable responses to identical stimuli, depending
upon the excitation state of the thalamo-cortical cells.
Conclusions
It is possible that changes in behavioral and
physiological responses following a DC lesion have arisen
through a variety of mechanisms at a number of neural loci.
Reduction in the amplitude and enhancement of frequency-
dependent suppression of cortical evoked potentials could
have resulted from; 1) an overall decrease in total inputs
to the cortex and 2) a selective reduction in drive from RA
and PC afferents that are present in the DCs. It is also
possible that the extent to which the spared spinal pathways
followed high frequency stimulation contributed to the
deficits; however, it is unlikely that this was the sole
determining factor, given that the frequency suppression in
the spared pathways was small at 10 pps. Another likely
candidate for a locus of the deficit is the thalamus. There
are specialized excitatory and inhibitory influences in the
thalamus that are controlled by input from the dorsal column
nuclei and other brainstem centers that shape the output to
the cortex. To further elucidate these mechanisms
additional studies involving single unit analysis at
multiple sites within the nervous system is required.


126
until about 220 days after the recording implant.
Monkey C also showed an significant (p<0.05) increase
in the p90 amplitude following a DC lesion, although this
was not as large an increase as for monkey F. Figure 4-4
shows this result in which p90 amplitude in response to a
1.5 pps mechanical stimulus to the right foot is plotted as
function of days following the right DC lesion. The left
foot was about 50% deafferented by the right DC lesion (see
Figure 3-2). This foot showed no significant increase in
amplitude after the lesion; however, time was a significant
variable (p<0.05).
Monkey S showed an insignificant increase in p90
amplitude after the lesion; however, there was a significant
change (p<0.05) in amplitude over time in response to
electrocutaneous stimulation following the lesion (Figure 4-
5). The p90 response to the mechanical stimulus, although
it was similar in shape to the electrocutaneous response,
did not vary significant over time (Figure 4-6).
Since there was a significant change or increase in the
p90 amplitude over time in each of the three animals under
some condition, these specific instances will be combined
below in an effort to describe the shape of this effect when
it occurs. Also, this procedure facilitated comparisons
ywith the effect of time on other peaks and on the potential
recorded from normal cortex. Before the results from each
animal were combined, the responses were normalized as
described in the Methods.


A


CHAPTER 1
GENERAL INTRODUCTION
Since the early 1900s investigators have attempted to
use clinical findings in patients with compromised dorsal
columns (DC) to infer the role of this pathway in
perception. These observations suggested that a lesion of
the DCs affects the ability of a patient to detect and
discriminate among a variety of tactile stimuli (see Nathan
et al.# 1986). However, for most of these patients, the
lesion involved other spinal pathways as well. In other
instances, most or all of the deficits appeared to recover
over time. Nevertheless, there are deficits that are common
to most accounts of DC interruption, and these are related
to processes that required temporal processing of
somesthetic stimuli. For example, tactile direction
sensitivity or the ability to identify letters written on
the hand (graphesthesia) can be affected by such a lesion.
Graphesthesia requires the patient to integrate the stimulus
over a few seconds. It also has been reported that a
repeated tapping stimulus or an object placed in the
patient's hand will fade over time. However, there are
differing accounts with respect to absolute threshold shifts
1


67
Table 3-1. Evoked potential latencies. Each block shows the peak latencies for each
component of the evoked potential in response to electrocutaneous, mechanical or ankle
stimulation before and after a DC lesion.
Monkey
Stimulus
Pre-les
Pre-les
Pre-les
Pst-les
Pst-les
Pst-les
/Foot
p20 (ms)
n50 (ms)
p90 (ms)
p20 (ms)
n50 (ms)
p90 (ms)
F/R
elec
21.0
48.0
96.0
23.0
48.0
93.0
F/L
elec
21.0
48.0
95.0
23.0
45.0
87.0
S/R
elec
19.5
55.0
83.0
23.0
56.0
94.0
Average
20.5
50.3
91.3
23.0
49.7
91.3
Std. Dev.
0.87
4.04
7.23
0.00
5.69
3.79
C/R
mech
23.0
58.5
85.5
25.0
46.0
92.0
F/L
mech
23.0
55.0
93.0
23.0
53.0
93.0
S/R
mech
22.0
47.0
89.5
26.0
42.0
90.0
Average
22.7
53.5
89.3
24.7
47.0
91.7
Std. Dev.
0.58
5.89
3.75
1.53
5.57
1.53
S/L*
ankle
17.0
33.0
88.0
-
-
-
S/R
ankle
-
-
-
19.0
55.0
77.0
C/R
ankle
19.0
55.0
84.0
19.0
47.0
87.0
Average
18.0
44.0
86.0
12.7
34.0
54.7
Std. Dev.
1.41
15.56
2.83
10.97
29.72
47.61
* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle
stimulation. All recordings were made (after a right DC lesion) on the control and deafferented
sides.


Figure 2-5. Compound action potentials recorded from
the AL tract of monkey D. (TOP) Responses to different
frequencies of contralateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the ipsilateral foot at 1.5 pps.


8
evoked potentials from acute Nembutal anesthetized monkeys
and found that there was an increased latency of 4-5 ms and
a decrease in amplitude of about 25% following DC section.
There was no change in the location of maximum activity from
intradermal electrocutaneous stimulation of the foot or the
hand. In the conditions when a mechanical stimulus was
used, the animal had already received a lesion of either the
ventral quadrant or dorsal quadrant before recordings were
made. This made it difficult to ascertain the contribution
of the DCs to the mechanical response.
A more recent study by Cusick et al.(1979) in monkeys
showed, under ketamine anesthesia, that acute DC section
almost completely eliminated the cortical evoked response to
exposed sciatic nerve stimulation. Following a 4-7 week
period after the lesion, there was a small increase in the
amplitude to about 25% of the preoperative control
amplitude. On the other hand, following a lesion of the DL
and AL pathways, sparing the DCs, there was no appreciable
attenuation of the evoked potential. Thus, the conclusion
from these studies is that the DCs provide sufficient input
to support a cortical evoked potential, but intact DCs are
not necessary for the presence of an evoked potential.
A few investigators have also looked at unit responses
following interruption of the DC pathway or dorsal
hemisection. Andersson et al. (1975) found, in lightly
anesthetized (pentobarbital) monkeys, that acute dorsal


51
was maintained between 37 and 38 degrees C with a heating
pad (K-pad) and warmed paraffin bags. After placement in a
stereotaxic head holding device, the head was shaved, and an
incision was made along the midline of the head. The bone
was scraped clean of tissue, and a single 1.4 cm hole was
made unilaterally over SI cortex with a trephine. Rongeurs
were used to extend the hole to the midline. The dura was
dissected away with iridectomy scissors and precision
forceps to expose the underlying pia. The cortex was then
bathed in artificial cerebral spinal fluid (CSF; Merlis,
1940) .
Recording. A recording chamber was mounted over the
opening with stainless steel screws and dental acrylic. It
was filled with artificial CSF and closed-off with a device
designed to hold a recording electrode and microdrive. This
setup formed a tight seal, but it allowed the electrode to
be positioned anywhere within the chamber, while keeping
track of the x-y coordinates to within 1/4 mm. The head was
then supported by a screw imbedded in the dental acrylic on
the skull, and the ear and eye bars were removed.
Electroencephalogram (EEG) electrodes were attached to two
screws that had been threaded into the skull over the
frontal and occipital cortices. The EEG was then
differentially amplified (10,000x), filtered (low-pass 40
Hz) and displayed continuously on an oscilloscope. Once the


Figure 4-10. Time course (days) of changes in the
evoked potential amplitude before a DC lesion in 3
monkeys. The p90 responses of the animals were
normalized (see Methods). Recordings over SI cortex on
both sides of the cortex are shown. Solid line is a
least-squares-fit to the data points.


153
contribute to changes in the amount or types of information
getting up the cord to the cortex. This is a situation
analogous to the present study, where a DC lesion partially
deafferents a portion of rostral somatotopic maps.
If the changes following DC-deafferentation were
derived from subcortical structures (i.e. the thalamus or
spinal cord), then it follows that a change in the evoked
potential should be evident in the first peak (i.e. the
input to and depolarization of layer IV). However, in the
present experiment, significant changes were observed in all
the animals in only the late (p90) peak. The early peak
showed an increasing trend, but it was not statistically
significant. Thus, it appears that the recovery was a
cortically mediated phenomenon. It is also possible that
there was a subcortical component that contributed to the
changes in cortical potential, but it was too small to be
detected with the evoked potential method.
Summary. There was a change in the amplitude of the
p90 component of the somatosensory evoked potential
following interruption of the DC pathway. This effect was
significant when the potential amplitude was large enough to
rise above the noise and when the recording electrodes had
not been implanted for more than 150 days. When the results
from the three animals were combined, the function showed a
precipitous increase in amplitude from 10 to 20 days post
lesion that corresponded with behavioral recovery on a


p90 amplitude (uV)
140
monkey F
monkey S
monkey C


122
Stimulation and Recording. On a daily basis,
recordings were made in response to electrocutaneous and
mechanical stimulation of the thenar eminence of the foot.
The signals were amplified and saved on magnetic tape for
off-line analysis. The amplifier was calibrated once a week
to ensure that there was no drift in the amplification over
time. The signal was also averaged on-line to monitor the
evoked potential during each recording session.
Data analysis. All data were analyzed off-line. The
"raw" evoked potential records were read off magnetic tape,
low-pass filtered (100 Hz), and digitized (1000 Hz, 1 ms bin
width) by commercially available software and an A-D board
(RC Electronics). The digitized records were converted into
ASCII files for further analysis by software written in 'C
(by the author).
The evoked potentials were first analyzed by discarding
any evoked potential traces that fell outside of a user
specified amplitude window (usually > + 300 uV). This was
intended to reject traces that contained movement artifact.
The remaining traces were then compressed and saved on disk.
Across days, these compressed files were then copied
together in series for analysis. The average amplitude of
the p20, n50 and p90 peaks from each recording session (day)
were plotted as a function of days post-lesion and were
tested to determine whether the slope was significantly


61
line) and SE (dashed lines) of the response at each time
point are shown for 320 stimulus presentations collected
over five separate days. The latencies of the different
peaks were approximately the same as for mechanical
stimulation and electrocutaneous stimulation to the foot
(Table 3-lc). In this Figure, the stimulus artifact is a
small negative deflection at 0 ms.
Averaged responses to different frequencies of ankle
stimulation are shown in Figure 3-14 for normal cortex and
Figure 3-15 for the DC deafferented cortex. In the normal
cortex, p20 remained relatively constant with changes is
stimulus frequency, whereas p90 suppressed with increasing
frequency. Following the DC lesion, there was about a 40%
reduction in the amplitude of the p20-n50 complex at all
frequencies (Figure 3-16). After the lesion, the p90-n50
complex showed about a 50% reduction in amplitude at 1.5 pps
but only a 10-15% reduction in amplitude at 10 pps. Both
the p20-n50 and p90-n50 complexes showed a significant
(p<0.01) decrease in amplitude following the lesion. The
individual animals also showed this effect (see Tables 3-2
and 3-3).
The frequency-dependent suppression following the DC
lesion was similar to the pre-lesion condition. There was a
20-50% reduction at 10 pps relative to 1.5 pps for both
complexes (Figure 3-17). One of the animals (monkey S)
showed a significant difference in slope for the p20-n50


124
3, Figure 3-1). The DC lesions are shown in Figure 3-2 and
were all complete. See Chapter 3 (Histology) for further
details.
Grasping
Two animals learned to grasp food with each foot; a
third animal was unable to learn the task. The averaged
results from the two animals, tested once a week, are shown
in Figure 4-1. This Figure shows, on the top, the effect of
a DC lesion on the percent successful attempts at grasping
each food item (foot ipsilateral to lesion). On the bottom
the control (contralateral) foot is shown. Both animals
showed a significant (p<0.05) decrease in the percentage of
successful attempts following the DC lesion from 98%+2%
(monkey C) and 80%+12% (monkey S) on the 3 sessions (weeks)
before the lesion to 60%+10% (monkey C) and 40%+12% (monkey
S) on the 3 sessions immediately after the lesion.
The latency results showed that the animals' successful
grasps took slightly longer to make after the lesion.
Monkey S averaged 3.9+0.5 s in the three sessions before the
lesion, whereas she averaged 4.4+0.3 s in the three sessions
after the lesion. This was not a significant increase.
However, monkey C showed a significant (p<0.01) increase
following the lesion. She went from 3.1+0.3 s on the three
sessions before surgery to 5.6+0.7 s on the three sessions
after the lesion.


151
amplitude over days in all the potentials measured. This
animal had received the recording implant more than 150 days
before the second lesion, and the recordings continued out
to nearly 220 days after the implant. Since there was a
decrease in all of the peaks on both sides following the
second lesion, it is likely that there was a degenerative
change in the recording properties of the implanted
electrodes over this time period.
These results provide evidence for functional recovery
from interruption of a major spinal pathway. This lesion
spared input from the periphery to alternative pathways with
central connections that run separately but have converging
inputs on to DC-lemniscal projection cells. Previous
investigators of functional recovery have generally used a
different model involving complete interruption of input
from a peripheral region. These peripheral lesions (e.g.,
Merzenich et al., 1984; Pons et al., 1991) produce both
short term (several days) and long term (months or years)
changes in the somatotopic map of the body after digit
amputation or dorsal rhizotomy (C2-T4). It was argued that
the short term changes (on the order of a few mm) could be
the result of alterations in synaptic efficacy at the
cortex; however, the long term changes ( > 1 cm) were
thought to arise from regions of the nervous system that
possess a smaller somatotopic map than the cortex.
For example, the thalamus (Rausell et at., 1992) showed


59
except for 10 pps, where successive responses interacted.
There was also a shift in the n50 minimum to an earlier
latency at frequencies between 2.5 pps and 5 pps. The
effect of a DC lesion on the responses to electrocutaneous
stimulation was to decrease the overall amplitude, though
not to the extent seen for mechanical stimulation (shown in
Figures 3-3 and 3-4). This improvement in the post-lesion
signal-to-noise ratio provided an opportunity to examine
frequency-dependent suppression in the absence of a floor
effect, in contrast to the response from the mechanical
stimulus.
Figure 3-11 shows the effect of a DC lesion on averaged
frequency-response amplitudes, for both the p20-n50 (top)
and p90-n50 (bottom) complexes. The p20-n50 complex was
reduced in amplitude by 60% or more at all frequencies post
lesion relative to the pre-lesion amplitude at 1.5 pps
(p<0.01). This decrease in amplitude was also significant
(p<0.01) for the p20-n50 complex in each of the three
animals. The y-intercept was not significantly altered for
the p90-n50 complex; however, since the average function was
not linear, this was not a valid test. When the difference
between the pre-lesion mean amplitude (across frequency) and
post-lesion mean amplitude of the p90-n50 complex was tested
for significance (t-test), there was a reliable difference
between means (p<0.05). One animal (monkey S) that had a
relatively linear function showed a significant change in


91
Ankle stimulation
30I
-100
-50
~~50 OO 1~50 200 250
time (ms)
o


p90 amplitude (uV)
138
40 -i
Monkey S
mechanical stimulus
30-
20-
10-
o-
A
A
-10-
0
I I I I I I I I I I
10 20 30 40 50 60 70 80 90 100
days postlesion


I
Monkey C
T7-T8
R
R
Monkey S
T8-T9
Monkey F
T7
CTi
Monkey F
T3-T4
R


41
Summary
These experiments demonstrated, through compound action
potentials recordings from large populations of spinal
fibers, that the extent of suppression for the different
pathways at 10 pps is similar. In the most extreme case,
the AL pll response was 70% of standard amplitude in
contrast to no suppression for the DC response (100% of
standard). Thus, it is likely that the pathways spared of a
DC lesion could reliably carry 10 pps stimulus up the cord.
However, at 50 pps there were large differences in the
frequency-dependent suppression of different pathways.
If any of the long spinal tracts were to be compromised
in some way (i.e. by a lesion), it is possible that, at the
cortex, there would be a decreased response amplitude,
because some percentage of the input to cortex was lost. It
is also possible, given the small difference (ca. 20%) in
slope between the DC and other pathways, that there would be
a concomitant change in slope of the frequency-response
function at the cortex following a DC lesion. If these were
indeed the outcomes of cortical recordings, then the animal
in a behavioral task might require a larger stimulus for
detection and could reveal an alteration in threshold with
stimulation frequency.


121
Subjects and Training. The subjects were the three
female stumptailed macaques that were used in the awake
recordings (Chapter 3). Recordings were obtained five or
six days a week. The animals were led into the laboratory on
a leash and seated comfortably in a plexigls primate chair.
They were gradually adapted to the primate chair and the
stimulation.
Two of the animals were also trained (once a week) on a
grasping task before the DC lesion was made. Grasping has
previously been shown (Vierck, 1978a) to be affected by such
a lesion and to reveal considerable recovery with time.
Therefore, this provided an assay for the integrity of the
lesion and for recovery of function following the lesion.
The animals were trained to pick up banana slices and small
marshmallows with each foot. The number of successful
attempts was noted, and, on successful attempts, the time it
took (latency) for the animal to place the food in its mouth
(latency) was measured with a stopwatch.
Surgery. Following chair training, epidural recording
electrodes were implanted over SI cortex. This was done
under sterile conditions at the University of Florida animal
surgery facility. After pre-lesion data were collected, a
unilateral interruption of the DC was made at a mid-thoracic
level (see Chapter 3 Methods for details).


53
Stimulus frequencies were 1.5, 2.5, 5, 7.5, and 10 pps.
Histology. At the end of each experiment, the animal
was given an overdose of sodium pentobarbital (195 mg i.v.)
and perfused through the heart. The stumptails were
perfused with saline and 1 ml/L of heparin sulfate, and then
with 10% formalin. The rhesus monkeys were perfused first
with warmed (36 degrees C) phosphate buffer (7.4 pH) and
heparin sulfate, and then with fixative (2% paraformaldehyde
and 2.5% glutaraldehyde). This was followed by a mixture of
fixative and 10% glycerol and rinsed with 10% glycerol in
phosphate buffer. The brain and spinal cord were removed,
and the cortex was photographed. The spinal cord and cortex
were blocked and cryo-protected in 30% sucrose (or glycerol)
and 10% formalin for a minimum of 1 week. Frozen sections
were cut at 50 urn, and stained with cresyl violet. In
animals with DC lesions, the extent of the lesion in the
cord was reconstructed with camera lucida drawings.
Data Analysis. Averages were compiled on-line from
100-150 stimuli, converted to ASCII files and saved on disk
for later analysis. The data were analyzed with spreadsheet
software where peak values of n20 were computed relative to
a baseline value. The baseline was taken as the maximum
amplitude between about 10 and 15 ms after the stimulus.
For each recording location, evoked potential amplitudes


6
However, it has been demonstrated in acute monkey
preparations that an SI cortical evoked potential is smaller
in amplitude but still intact (Andersson et al., 1972)
following interruption of the ipsilateral (to the stimulus)
DCs and the contralateral AL tract, sparing only the
ipsilateral DL tract. This result was obtained in response
to light mechanical stimulation of the skin. Although it is
still not clear the extent to which the DL and AL pathways
carry temporal information, it is apparent that both
pathways carry information that is cutaneous in nature.
The DC, DL and AL tracts synapse in the thalamus before
tactile information is transmitted to the cortex, where it
contributes to normal perception. All three long tracts
have converging inputs onto the ventro-basal complex of the
thalamus (Berkley, 1980; 1983), providing sites for
interaction among the various pathways. Indeed, a number of
studies have demonstrated the existence of excitatory and
inhibitory interaction in the ventro-basal complex of the
thalamus (Anderson et al., 1964; Janig et al., 1979; Salt,
1989). These interactions can last from 50 to 500 ms,
depending upon the cells, and are thought to shape the
spatio-temporal profile of responses that are sent to the
cortex. Thus, removal of one of the inputs to this region
(e.g., a DC lesion) could lead to an imbalance between the
remaining excitatory and inhibitory inputs. This could
change neuronal integration (filtering) in the thalamus,


Figure 3-12. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
before and after a DC lesion (3 lesions). Amplitudes
are expressed as percent of either the pre-lesion or
post-lesion response to 1.5 pps. Error bars are + 1 SE.
(TOP) The amplitude of the p20-n50 complex. (BOTTOM)
The amplitude of the p90-n50 complex. Lines drawn
through data points are least-squares-fit.


3
in monkeys. Vierck (1974) showed that tactile direction
discrimination was hampered for up to 1 year following a DC
lesion, whereas simple detection of movement across the skin
showed only a transient deficit. Later, Vierck et al.
(1985) showed that monkeys trained to discriminate a 10 Hz
tactile stimulus from a 14 Hz stimulus could not
discriminate 10 Hz from 35 Hz following interruption of the
DC pathway, even after extensive retraining (1 yr). Animals
trained on the same task with lesions of the dorsal-lateral
(DL) and/or antero-lateral (AL) columns showed no such
lasting deficit. In a more recent study (Vierck et al.,
1990), normal monkeys could discriminate between stimulus
trains of 3 pulses (at 10 Hz; 200 ms total duration) from
trains of 5 to 7 pulses (400-600 ms duration); however,
following interruption of the DC pathway, the animals could
not discriminate trains of 3 pulses from trains of as many
as 35 pulses. Thus, it appears that tasks requiring
temporal processing of tactile input, at least in a range of
frequencies from 10-35 Hz, depend uniquely upon input from
the DC.
Anatomy and Physiology
When the DCs are compromised, somatosensory information
reaching the cortex must be carried by the remaining
pathways. The only other spinal pathways that are thought
to contribute significantly to perception are long


148
Averaged Blocks
~o
o
a>
Q_
10
~r
20
i i i i i i 1 1
30 40 50 60 70 80 90 100
days postlesion


13
the cortical surface where axons are contacting dendrites.
The second positive peak is derived from a more global
spread of information to association cortices. In this
condition, the SI cortex serves as a source and the other
cortical areas serve as sinks. This late positive potential
can be recorded over a large area of cortex (Arezzo et al.,
1981; Kulics and Cauller, 1986; Emerson and Pedley, 1990;
Allison et al., 1991).
Overview of Dissertation
The following chapters describe a series of experiments
that were designed to look at the effects of a DC lesion on
somatosensory evoked responses to repetitive stimulation.
These experiments describe physiological accompaniments of
the temporal discrimination deficits observed following such
a lesion. The second chapter looks at the extent to which
compound action potentials recorded in the three long spinal
tracts follow high frequency stimulation. It was expected
that such an experiment would provide evidence concerning
the origin of any frequency-dependent suppression that might
be obtained at the cortical level in the absence of the DC
pathway. The third chapter describes changes in the evoked
cortical response and its frequency-dependent suppression
following the DC lesion. The fourth chapter follows the
evoked potential as it changes over months following the
lesion. This experiment was designed to correlate changes


Figure 4-7. Time course (days) of changes in the
evoked potential amplitude following a DC lesion for
three monkeys. The p90 response of the animals were
normalized (see Methods). Recordings over SI cortex
contralateral to the DC lesion are shown. Solid line
is a least-squares-fit to the data points.


Abstract of Dissertation Presented to the Graduate School of
the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy
EFFECTS OF A DORSAL COLUMN LESION ON SOMATOSENSORY EVOKED
POTENTIALS IN PRIMATES
By
James Carl Makous
May 1993
Chairperson: Charles J. Vierck, Jr.
Major Department: Neuroscience
A dorsal column (DC) lesion has a significant lasting
effect on behavioral tasks that require temporal processing
of tactile information (i.e. frequency and duration
discrimination). These experiments describe physiological
correlates of the behavioral deficits in temporal
discrimination observed in primates following DC lesions.
In experiment 1, compound action potentials were
recorded from the major ascending white matter tracts of the
cord. These experiments determined the extent to which
different sensory pathways of the spinal cord responded to
high frequency stimulation. At 10 pulses per second (pps)
v


4
somatosensory pathways (long tracts) in the dorsal-lateral
(DL), and antero-lateral (AL) columns (Vierck, 1984). Long
tracts in the DL column ascend the spinal cord ipsilateral
to the primary afferent fibers (Rustioni et al., 1979),
whereas the AL tract fibers cross the midline near the root
entry level and ascend the spinal cord in the
antero(ventral)-lateral quadrant of the spinal cord,
contralateral to the primary afferent fibers (Trevino and
Carstens, 1975).
The majority of the fibers constituting the DL and AL
pathways have their cell bodies in the dorsal horn, where
there are a number of modulatory influences. For example,
Jimenez et al. (1987) have shown that there are descending
fibers originating in the brainstem reticular formation and
red nucleus that have presynaptic inputs onto cutaneous
primary afferents entering the dorsal horn. Furthermore,
cutaneous information is carried up the cord to the
reticular formation (Salibi et al., 1980) and the red
nucleus (Berkley, 1986) via the DC nuclei. Therefore, a DC
lesion could result in a change in the regulation of
information entering the dorsal horn, owing to a loss of DC
connections with the reticular formation and red nucleus.
There is also evidence that primary afferents synapsing
in the dorsal horn are directly inhibited by cutaneous
stimulation (Wall, 1958; Janig, 1968). For example,
following cutaneous stimulation, there is an inhibition of


Amplitude
Mechanical stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
10 pps
1.5 pps
U>


Figure 2-2. Reconstruction of the DC lesion for one monkey E. The
drawing was made from a projection of the stained spinal cord section.
The cross-hatched area represents the extent of the thoracic lesion
(T12).



103


47
pps to 10 pps for both electrocutaneous and mechanical
stimuli. The number of presentations of each stimulus
condition varied from 64-320, depending upon the stimulus
frequency.
For the electrocutaneous stimuli, the output of the S88
passed through a stimulus isolation unit, a constant current
unit, a current monitor, and then out to the animal. Each
animal received stimulation of the foot via two wells in
adhesive foam pads that were filled with either Sergi-lube
or electrode paste. The amplitude of stimulation (4 mA) was
chosen so as to elicit a recognizable evoked potential
without causing any discomfort to the animals or a
perceptible muscle twitch. The duration was short (0.2 ms)
to minimize the stimulus artifact. Two animals received
electrocutaneous stimulation of the ankle with ring
electrodes made of aluminum foil. Each 3/4 in. strip of
foil was coated on one side with sergi-lube, wrapped around
the ankle or the calf, and held in place with adhesive tape.
Stimulus amplitude was 12 mA, which caused a slight twitch
of the foot during about half of the recording sessions.
Mechanical stimulation was provided by a vibrator (Ling
102) that was driven by a locally designed and constructed
driver that took the voltage output of the S88 (a 10 ms
pulse) and matched it to the current requirements of the
vibrator. The vibrator was mounted on a track that could be
vertically advanced by turning a screw with a 1 mm pitch. A


(% control: 1.5 pps) Amplitude (% control: 1.5 pps)
99
100-i
80-
60-
P20-N50
D
40-
20-
0 2 4 6 8 10
Stimulus frequency (pps)
P90-N50


166
Franzen, O., Offenloch, K. (1969) Evoked response
correlates of psychophysical magnitude estimates for
tactile stimulation in man. Exp. Brain Res. 8:1-18.
Gardner, E.D., Morin, F. (1953) Spinal pathways for
projection of cutaneous and muscular afferents to the
sensory and motor cortex of the monkey (Macaca
mulatta). Am. J. Physiol. 174:149-154.
Gardner, E.D., Morin, F. (1957) Projection of fast
afferents to the cerebral cortex of monkeys. Am. J.
Physiol. 189:152-158.
Garraghty, P.E., Kass, J.H. (1991) Functional reorganization
in adult monkey thalamus after peripheral nerve injury.
NeuroReport 2:747-750.
Goldberger, M.E., Murray, M. (1982) Lack of sprouting and
its presence after lesions of the cat spinal cord.
Brain Res. 241:227-239.
Hahn, J.F. (1958) Cutaneous vibratory thresholds for
square-wave electrical pulses. Sci. 127:879-880.
Janig, W., Schmidt, R.F., Zimmerman, M. (1968) Two specific
feedback pathways to the central afferent terminals of
phasic and tonic mechanoreceptors. Exp. Brain Res.
6:116-129.
Janig, W., Spencer, W.A., Younkin, S.G. (1979) Spatial and
temporal features of afferent inhibition of
thalamocortical relay cells. J. Neurophysiol.
42(5):1450-1460.
Jimenez, I., Rudomin, P., Solodkin, M. (1987) Mechanisms
involved in the depolarization of cutaneous afferents
produced by segmental and descending inputs in the cat
spinal cord. Exp. Brain Res. 69:195-207.
Kulics, A.T. (1982) Cortical neural evoked correlates of
somatosensory stimulus detection in the rhesus monkey.
Electroencephalogr. Clin Neurophysiol. 53:78-93.
Kulics, A.T., Cauller, L.J. (1986) Cerebral cortical
somatosensory evoked responses, multiple unit activity
and current source-densities: their interrelationships
and significance to somatic sensation as revealed by
stimulation of the awake monkey's hand. Exp. Brain
Res. 62:46-60.
Levitt, M. Schwartzman, R.J., (1966) Spinal sensory tracts
and two-point tactile sensitivity. Anat. Rec. 154:377.


39
tracts was as expected. The DC pathway had the shortest
latency to peak (10.3 ms), whereas the DL and AL had longer
latencies (10.7 and 10.8 ms, respectively). Since these
latter two pathways comprise post-synaptic populations of
fibers and do not include primary afferents (in contrast to
the DC), it follows that longer latency responses were
obtained from the lateral columns. The AL and DL responses
should be nearly 1 ms later than responses from the DC,
given the mandatory synapse (i.e. delay of 1 ms) in the
dorsal horn. It is possible that a combination of factors
contributed the 0.5 ms difference actually observed. For
one, the DC response from monkey E was about 1.5 ms longer
than the DC response from the other two animals. Since the
DCs also have a large number of post-synaptic cells arising
from the dorsal horn (Rustioni et al., 1979), it is possible
that this recording was made from a division of the DC with
a preponderance of post-synaptic fibers. Since there was a
DC lesion in monkey E on the contralateral side, responses
arising from the control foot were not a determining factor
for this electrode placement, as it could have been in the
other recordings. Another factor that could have
contributed to the small difference between the DC and AL
latencies was the large bin width of 0.3 ms.
In addition to peaks at 11 and 14 ms, there was a peak
at 15 ms that appeared only at 25 pps in the AL response,
but it was abolished at 50 pps. It is possible that this


Amplitude (se control: prelesion) Amplitude (se control: prelesion)
87
i 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
o
o
Stimulus frequency (pps)
n
10
lesion
-lesion
lesion
-lesion


laboratory space and equipment all of which were in short
supply (save for his knowledge). I also thank Babbette
Botchin and Dan Thiel for expert veterinary care.
Last, I would like to thank my family; my father whose
advice both personal and professional has never steered me
wrong; and my wife, Elizabeth, who has been an endless
source of love, support and inspiration during these years
of training.
iii


Amplitude
electrocutaneous stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
10 pps
1.5 pps
00
CO


CHAPTER 3
RECORDINGS FROM THE CEREBRAL CORTEX
Following a DC lesion, the information arriving at the
cortex is limited by the extent to which the spared pathways
(DL and AL) carry somatosensory information and by the
responsivity of partially deafferented central relays of the
spared input. Since there are behavioral deficits in
discrimination of repetitive stimulation at frequencies of
10 pps and above, it should be instructive to look at
cortical responses to 10 pps before and after a DC lesion.
There are several possible outcomes of these recordings:
1) It is possible that, following a DC lesion, the
cortical evoked potential is diminished in amplitude.
Although this has been the subject of some dispute (see
Chapter 1), it is likely that a removal of one of the long
tracts would result in the diminution of the overall amount
of input to cortex. This result would suggest that an
elevation of detection thresholds could be seen following
the lesion. However, this has not been found with
application of von Frey hairs to the sole of the foot
(Vierck, 1977) or with brush stimuli to the lateral calf
(Vierck, 1974). Thus, it appears that input from infrequent
42


p20 amplitude (uV)
142
50 n
Combined response (normalized)
deafferented cortex
40-
x
30-
x
20-
10-
0-
-10
0
x A
monkey C
10 20 30 40 50 60 70 80 90 100
days postlesion


125
Recordings
All three animals showed a significant change in p90
amplitude over three months following a DC lesion under one
of the recording conditions. Two animals (monkey F and
monkey C) showed a significant (p<0.05) increase over time
in p90 amplitude following the lesion, whereas monkey S
showed that time was a significant (p<0.05) variable. On
the other hand, some stimulus and recording conditions did
not show significant increase or change over time. Monkey S
showed no significant effect of time in response to the
mechanical stimulus, and monkey F showed a significant
decrease in all potentials on both sides of the cortex after
the second lesion. Since there was such a diversity of
results, each condition will be discussed separately.
Monkey F showed the largest increase in p90 amplitude
following the first (right) DC lesion. Figure 4-2 shows the
response over time to electrocutaneous stimulation (1.5 pps)
of the right foot. This increase was significant for p90
(p<0.05) but not for either of the other two peaks on the
deafferented side or for any peak on the control side.
These recordings occurred over 90 days after implanting the
recording electrodes. However, following the second lesion,
which occurred at about 150 days after the implantation,
there was a continuous decrease in the amplitude of all
peaks recorded on both sides of the cortex (Figure 4-3 shows
the p90 response only). These recordings were collected


CHAPTER 5
GENERAL DISCUSSION
The changes in the evoked potential following a DC
lesion, taken together with clinical findings in humans and
behavioral results in non-human primates suggest new
implications for the role of the DCs in conscious
perception. Not only are the DCs essential for normal
temporal processing of information, but they may also be
involved in the perception of static skin indentation. It
is possible that these deficits could arise at any one of a
number of locations along the neuraxis.
Neural Mechanisms
Nathan et al. (1986) described two cases where
interruption of the DCs affected the patients ability to
feel the ongoing presence of a object placed in the hand.
These patients appeared to have difficulty perceiving
differences between graded pressure stimuli and feeling a
repeated tapping stimulus. Although these clinical findings
are difficult to interpret, owing to inadequate
psychophysical techniques and because of pathology involving
155


Amplitude ($g control: normal) Amplitude (% control: normal)
97
oH 1 , ,
0 2 4 6 8 10
Stimulus frequency (pps)
100-i
80-
60-
40-
20-
P90-N50
"0
0
0
I 1 1 1 1 1 1 1 1
2 4 6 8 10
Stimulus frequency (pps)
normal
deafferented
normal
deafferented


112
There was no systematic variation in frequency
suppression of the n20 response at different locations
within the SI cortex. The mean amplitude of the n20
potential at 10 pps relative to 1.5 pps (control frequency)
was not reliably different in the deafferented cortex (66.8%
+ 30%; +SD) than in the normal cortex (63.2% + 14%). There
also was no difference between the recordings obtained in
response to foot or ankle stimulation (save for latency).
However, the amplitude at 10 pps (relative to 1.5 pps) in
the deafferented cortex was significantly more variable
(p<0.05) than in the normal cortex (Figure 3-22).
These results indicate that there was an increased
variability in the responsiveness of the cortex to
electrocutaneous stimulation of either the foot or the ankle
following a DC lesion. There did not appear to be any
difference between the normal and deafferented cortex in the
extent to which the n20 potential was suppressed at 10 pps.
However, the lesion did result in a significant increase in
the latency to the n20 peak following ankle stimulation.
DISCUSSION
The above results showed that interruption of the DCs
led to a decrease in amplitude of the epidural evoked
potential under all stimulus conditions and frequencies.
The early components of the post-lesion potentials showed a


117
cortex. Since the first peak was affected, it is likely
that the increased variability arose from subcortical
structures such as the thalamus.
In the awake recordings there was significantly greater
suppression at 10 pps, relative to 1.5 pps, in the DC-
deaf ferented cortex. It is not clear why the acute
recordings did not show a similar effect. It is possible
that the anesthetic raised the level of the noise during
these experiments, which in turn may have led to a floor
effect, similar to that seen in the awake recordings in
response to mechanical stimulation (see Figure 3-6).
Similarly, recordings from a restricted area of the cortex
in the acute experiments may have reduce the signal-to-noise
ratio. It is also possible that averaging across all the
locations of acute recordings masked an effect that was
present in only certain locations (e.g., at the center of
the representation of the distal extremity).
The increased variability in frequency-dependent
suppression at different recording locations in DC-
deafferented cortex is consistent with previous recordings
from units in SI cortex that responded to brush stimulation.
Vierck et al. (1990) found an increased variability in the
driving of DC-deafferented cortical units by each stimulus
in a repetitive train. Therefore, it is possible that the
focal evoked potentials were drawing from different groups


60
the y-intercepts (p<0.01) of the functions relating
amplitude of the p90-n50 complex to frequency (see also
Tables 3-2 and 3-3).
The DC lesion led to an increased frequency-dependent
suppression of the p20-n50 response to electrocutaneous
stimulation of the foot (Figure 3-12, top). This effect was
not observed in the p90-n50 complex (Figure 3-12, bottom).
The slope of the frequency response function was
significantly (p<0.01) steeper in the post-lesion cortex
than the pre-lesion cortex for p20-n50. There was about a
20% greater reduction in amplitude at 10 pps following the
lesion, relative to the pre-lesion suppression by 10 pps.
This frequency-dependent suppression was true for two of the
three individual lesions (p<0.05; see Table 3-2).
Thus, the p20-n50 complex of the evoked responses to
electrocutaneous stimulation was significantly decreased in
amplitude by a DC lesion, and frequency-dependent
suppression was increased. This was also true for the p90-
n50 complex in amplitude but not for frequency-dependent
suppression.
Ankle stimulation. A normal evoked potential, recorded
over SI cortex (monkey C) in response to electrocutaneous
stimulation of the ankle (0.2 ms, 12 mA, 1.5 pps), is shown
in Figure 3-13. This potential was recorded from the
electrode location shown in Figure 3-1. The average (solid


Figure 3-18. Photograph of a sagittal section, taken 7 mm from the
midline of a Macaca nemestrina (Winters et al., 1969; page 13, panel
L7) Reproduced with permission of publisher. (CS = central sulcus; pcs
= post-central sulcus; IPS = intra-parietal sulcus; CgS = cingulate
sulcus)


170
York, D.H. (1985) Somatosensory evoked potentials in man:
Differentiation of spinal pathways responsible for
conduction from the forelimb vs hindlimb. Progress in
Neurobiology 25:1-25.


32
Spinal cord recordings
dorsallateral
-20-
r \ ^ x N
/ \ x
v /
-ii ; r
10
time (ms)
control
foot
0
1 r
5
-1 1ii 1 1
15 20


Figure 4-9. Time course (days) of changes in the
evoked potential amplitude following a DC lesion for
two monkeys. The p90 responses of the animals were
normalized (see Methods). Recordings over normal SI
cortex ipsilateral to the DC lesion are shown. Solid
line is a least-squares-fit to the data points.


Figure 4-8. Time course (days) of changes in the
evoked potential amplitude following a DC lesion for
three monkeys. The p20 responses of the animals were
normalized (see Methods). Recordings over SI cortex
contralateral to the DC lesion are shown. Solid line
is a least-squares-fit to the data points.


Figure 3-5. Post-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 to 10 pps (right of each trace).
From 1065 to 1183 averages were accumulated from recordings on 20 days.


7
which, in turn, could result in a change in perception.
A number of studies have attempted to ascertain the
role of the various spinal cord pathways in generating a
cortical response through evoked potential measurements. In
general the results have been inconclusive, owing to the
variety of stimuli used, the lack of repeated measures
within individual animals, and the different kinds of
anesthesia.
Gardner and Morin (1953; 1957) showed in pentobarbital
anesthetized monkeys that neither chronic nor acute DC
section altered the latency or threshold of somatosensory
cortical evoked potentials. In this study, they used
electrical stimulation directly on dissected cutaneous and
deep nerves. It was not clear how they determined threshold
or the amplitude of stimulation. It is also possible that
direct stimulation of the nerve recruited predominantly the
large diameter fibers originating in muscle (York, 1985).
Eidelberg and Woodbury (1972) also found no change in
the amplitude or latency of the cortical evoked potential
following chronic (>4 weeks) or acute DC or dorsal quadrant
lesions in monkeys. They stimulated the radial nerve
transcutaneously at 1-3 mA under chloralose anesthesia.
Unfortunately, these results were compared to unoperated
controls rather than preoperative controls from the same
animal.
On the other hand, Andersson et al. (1972) recorded


101
lesions in monkeys F and C. Monkey R6 had a complete lesion
of the right DC between T4 and T5. There was a slight
involvement of the left DC and the right DL tracts, but
there was little involvement of the spinal grey matter.
Since this was a long term lesion (> 1 yr), there was
noticeable shrinkage of the right DC.
Recordings. The waveforms shown in Figure 3-21 were
recorded at two different locations in normal cortex
following foot stimulation and ankle stimulation. This
Figure shows that responses to the 10 pps stimulus was
suppressed relative to the 1.5 pps stimulus for both the
foot and ankle stimulation; this was typically the case.
The first negative peak was present most reliably across all
locations in cortex. The mean latency of the first
potential from the thenar in the no lesion condition was
22.0+0.79 ms (+SE), whereas the latency in the presence of a
lesion was 23.6+0.83 ms (not significant). The latency from
the ankle stimulus was 17.6+0.34 ms in the absence of a
lesion and 20.0+0.60 ms with the lesion (significant,
p<0.01). Although the ankle stimulation, with or
without a lesion, yielded a n20 latency that was about 4 ms
shorter than the thenar stimulus (significant, p<0.01), this
potential probably arose from the same generators under both
stimulus conditions. It is likely that the shorter latency
resulted from the larger stimulus to the ankle (typically 12
mA versus 5-6 mA).


Figure 3-3. Averaged pre-lesion evoked potential,
recorded over SI cortex in response to mechanical
stimulation of the foot (monkey S). Solid line
represents the average of responses to 210 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.


168
Salt, T.E. (1989) Gamma-aminobutyric acid and afferent
inhibition in the cat and rat ventrobasal thalamus.
Neurosci. 28(l):17-26.
Schwartz, M. (1976) Averaged evoked responses
encoding of perception. Psychophysiology
553.
and the
13(6):546-
Steriade, M., Jones, E.G., Llinas, R.R. (1990) Thalamic
oscillations and signaling. Wiley, New York.
Surmeier, D.J., Honda, C.N., Willis, W.D.,Jr. (1988)
Natural groupings of primate spinothalamic neurons
based on cutaneous stimulation. Physiological and
anatomical features. J. Neurophysiol. 59:833-860.
Tigwell, D.A., Sauter, J. (1992) On the use of isoflourane
as an anaesthetic for visual neurophysiology. Exp.
Brain Res. 88:224-228.
Trevino, D.L. Carstens, E. (1975) Confirmation of the
location of spinothalamic neurons in the cat and monkey
by the retrograde transport of horseradish peroxidase.
Brain Res. 98:177-182.
Uttal W.R. Cook, L. (1964) Systematics of the evoked
somatosensory cortical potential: A psychophysical-
electrophysiological comparison. Annals New York
Academy of Sciences. 112:60-80.
Vierck, C.J.,Jr. (1966) Spinal pathways mediating limb
position sense. Anat. Rec. 154:437.
Vierck, C.J.,Jr. (1973) Alterations of spatio-tactile
discrimination after lesions of primate spinal cord.
Brain Res. 58:69-79.
Vierck, C.J.,Jr. (1974) Tactile movement detection and
discrimination following dorsal column lesions in
monkeys. Exp. Brain. Res. 20:331-346.
Vierck, C.J.,Jr. (1977) Absolute and differential
sensitivities to touch stimuli after spinal cord
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Vierck, C.J.,Jr. (1978a) Comparison of forelimb and
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of behavioral neurobiology; (1) Sensory integration.
Ed. R. Bruce Masterton. Plenum Press, New York.


TABLE OF CONTENTS
Page
ACKNOWLEDGEMENTS ii
ABSTRACT v
CHAPTERS
1 GENERAL INTRODUCTION 1
Behavior 2
Anatomy and Physiology 3
Plasticity 10
Evoked Potentials 12
Overview of Dissertation 13
2 RECORDINGS FROM THE WHITE MATTER TRACTS
OF THE SPINAL CORD 15
Methods 16
Results 22
Discussion 38
3 RECORDINGS FROM THE CEREBRAL CORTEX 42
Methods 44
Results 54
Discussion 112
4 PHYSIOLOGICAL CHANGES DURING RECOVERY FROM
A DORSAL COLUMN LESION 119
Methods 120
Results 123
Discussion 150
5 GENERAL DISCUSSION 155
Neural Mechanisms 155
Conclusions 163
REFERENCES 164
BIOGRAPHICAL SKETCH 171
iv


Figure 2-4. Compound action potential recordings from
the DL tract of monkey D. (TOP) Responses to different
frequencies of ipsilateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the contralateral foot at 1.5 pps.


19
(insulation). The tip of the electrode was then briefly
touched against a hot soldering iron. This usually yielded
impedances in the range of 10 100 kohms (at 1000 Hz),
depending on the duration of contact with the hot iron.
Signals recorded in the spinal cord in response to
electrocutaneous stimulation were differentially amplified
(Bak, 10,000x) in reference to a muscle flap along the
margin of the surgical opening. The signals were digitized
(11 us, Vetter), and recorded on magnetic tape (VCR) for
off-line analysis. The signal was also filtered (3-300 Hz
pass-band) and averaged on-line (286-computer; RC
electronics software) to monitor the potential during each
recording session.
Procedure. The experimental procedure consisted of the
following. The electrode was lowered into each of the major
tracks of the cord after visualizing the dorsal root entry
zone and the midline under a dissecting microscope. For
dorsal column penetrations the electrode was positioned
sufficiently near the midline to evoke a large response to
ipsilateral stimulation of the foot without evoking a
response from the contralateral foot. Dorsal-lateral
penetrations were made slightly lateral to the dorsal root
entry zone and were shallow enough to record little or no
response from stimulation of the contralateral foot.
Antero-lateral penetrations were made slightly more lateral
and deeper than the DL penetrations, to maximize a response


Number of Observations
111
no lesion DC lesion
Response at 10pps relative to response at 1.5pps
(percent)


Amplitude (% control: 1.5 pps) Amplitude (sg control: 1.5 pps)
89
P20-N50
100-1
80-
60-
40-
20-
0-i 1 1 1 1 1 1 1 1 r-
0 2 4 6 8 10
Stimulus frequency (pps)
100-1
80-
60-
40-
20-
0 2 4 6
Stimulus frequency (pps)
t 1 1
8 10


11
T = thoracic; L = lumbar) produced large (> 1 cm) changes in
the area and location of cortex represented by the face
relative to control animals. That is, the face
representation invaded the area normally occupied by the
hand. It is not clear where the actual reorganization took
place; however, given the large shift in the cortical map, a
cortical mechanism is unlikely. A more likely locus could
be the spinal cord or thalamus, where the representations of
adjacent body parts are in closer proximity.
Rausell et al. (1992) also looked at the thalamus of
the monkeys used in the Pons et al. (1991) study. They
found a down regulation of gamma-aminobutyric-acid (GABA)
receptors in the deafferented thalamus relative to controls.
They also found changes in calcium binding proteins that are
specific for either lemniscal or nociceptive pathways.
Thus, it appears that there were long term changes in the
thalamus that accompanied the reorganization of the map at
the cortical level.
Changes in spinal cord have also been observed
following deafferentation. For example, Goldberger and
Murray (1982) observed sprouting in the cord following
dorsal rhizotomy in cats. They found an increased
projection to nucleus gracilis and to the spinal laminae
that normally received projections from the spared root.
However, there was no sprouting into areas not normally
receiving projections from the spared root. There also was


p90 amplitude (uV)
146
monkey F
monkey S
monkey C


Figure 3-4. Pre-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 10 pps (right of trace). From
210 to 297 averages were accumulated from recordings on 5 days.


169
Vierck, C.J.,Jr. (1984) The spinal lemniscal pathways. In
Handbook of the spinal cord. Ed. Robert A. Davidoff.
Marcel Dekker, Inc. New York and Basel.
Vierck, C.J.,Jr., R.H. Cohen and Brian Y. Cooper (1983)
Effects of Spinal tractotomy on spatial sequence
recognition in macaques. J. Neuroscience 3(2):280-290.
Vierck, C.J.,Jr., R.H. Cohen and Brian Y. Cooper (1985)
Effects of spinal lesions on temporal resolution of
cutaneous sensations. Somatosensory Res. 3(l):45-56.
Vierck, C.J.,Jr., Favorov, O., Whitsel, B.L. (1988) Neural
mechanisms of absolute tactile localization in monkeys.
Somatosensory Res. 6:41-61.
Vierck, C.J.,Jr., Whitsel, B.L., Makous, J.C., Friedman,
R.M. (1990) Soc. for Neurosci. Abst. 16:1081.
Wall, J.T. (1988) Variable organization in cortical maps of
the skin as an indication of the lifelong adaptive
capacities of circuits in the mammalian brain. Trends
in Neurosci. 11:549-557.
Wall, P.D. (1958) Excitability changes in afferent fibre
terminations and their relation to slow potentials. J.
Physiol. 142:1-21.
Wall, P.D. (1970) The sensory and motor role of impulses
travelling in the dorsal columns towards cerebral
cortex. Brain 93:505-524.
Whitsel, B.L., Petrucelli, L.M., Ha, H., Dreyer, D.A. (1972)
The resorting of spinal afferents as antecedent to the
body representation in the postcentral gyrus. Brain
Behav. Evol. 5:303-341.
Willis, W.D., Trevino, D.L., Coulter, J.D., Maunz, R.A.
(1974) Responses of primate spinothalamic tract
neurons to natural stimulation of hindlimb. J.
Neurophysiol. 37:358-372.
Willis, W.D., Maunz, R.A., Foreman, R.D., Coulter, J.D.
(1975) Static and dynamic responses of spinothalamic
tract neurons to mechanical stimuli. J. Neurophysiol.
38:587-600.
Winters, W.D., Kado, R.T., Adey, W.R. (1969) A stereotaxic
atlas for Macaca nemestrina. University of California
Press. Berkeley and Los Angeles, California.


37
50 pps, whereas the pll was not. Moreover, the pl4 appeared
to shift its latency at 25 pps, which suggests the existence
of yet a third peak that was unmasked at 25 pps. Both
animals with a pl4 response exhibited this phenomenon. The
pll response from the control foot was 20% of the standard
response to stimulation of the experimental foot, which was
not uncommon for this electrode location.
Averaged (across animals) frequency-response functions
for each of the tracts are shown in Figure 2-6. The most
obvious result was that responses from the DL and AL columns
did not follow the 50 pps stimulus as well as the potentials
within the DC pathway. However, at 10 pps the late response
from the AL tract (pi4) was not significantly different from
the DC response. In fact, there was even a slight (but not
significant) augmentation of the pl4 response at 2.5 pps.
Beyond 10 pps, however, there was a precipitous drop off in
the response at pl4 to higher frequencies. The AL response
at pll showed a similar trend to the response from the DL
tract at the low frequencies, but beyond 10 pps the two
functions diverged. The DL response was never suppressed to
more than 70% of control at the highest frequencies, whereas
the pll response from the AL tract at 50 pps was down to 20%
of the standard amplitude.
Summary
In response to electrocutaneous stimulation of the


161
discussed above (Whitsel et al., 1972; Ferrington et
al.,1988; Downie et al.,1988; Surmeier et al.,1988).
However, the cortical response to electrocutaneous
stimulation at 10 pps was only suppressed by the lesion to
about 35% of the control amplitude (see Figure 3-11). This
finding, taken together with the fact that electrocutaneous
stimulation is less specific than a mechanical stimulus,
suggests that the electrocutaneous stimulus activates fibers
that do not carry purely tactile information. This line of
reasoning indicates that afferents supplying deep tissues
make a larger contribution to the DL and AL pathways than to
the DC pathway. Physiological recordings from the dorsal
columns have demonstrated this in both primates (Whitsel et
al., 1972) and cats (Dart and Gordon, 1973).
Thalamus
Another possible mechanism for the deficits in
processing of temporal information may result from changes
in the thalamus following a DC lesion. Ralston (1991) has
shown that medial lemniscal fibers arriving in the ventro-
basal complex of the thalamus have synapses on the proximal
dendrites of thalamic neurons that project to somatosensory
cortex. The same lemniscal cells also have synapses on
local GABA interneurons. These interneurons in turn have
synapses on the same cortical projection neurons as the
lemniscal fibers. Thus, a single thalamo-cortical cell


Figure 3-20. DC lesion from one of the monkeys used in the acute
recordings. The drawing was made from a projection of the stained
spinal cord sections. The cross-hatched area represents the extent of
the lesion.


12
a tendency for areas that are topographically organized to
not receive any sprouting fibers.
Thus, it appears that neural plasticity does exist in
the adult nervous system, and it is possible that changes
following injury to the brain or spinal cord could be taking
place at many possible points along the neuraxis. It is
likely, then, that a behavioral recovery following a lesion
could reflect changes in the neural connectivity in the
spared pathways.
Evoked Potentials
Evoked potentials are the summated neural response from
a group of neurons depolarizing and/or hyperpolarizing in
synchrony. The amplitude of the evoked potential is
proportional to stimulus amplitude under some stimulus
conditions (Beck and Rosner, 1968; Franzen and Offenloch,
1969; Kulics, 1982); however, this issue has been disputed
(Uttal and Cook, 1964; Schwartz, 1976). Evoked potentials
are often used as a diagnostic tool for the integrity of the
afferent pathways (Pillay, 1984). The first positive peak
in the somatosensory cortical evoked potential is thought to
arise from the depolarization of layer four (a current
sink), whereas the current source arises from the dendrites
at the surface of the cortex. The second peak (negative)
arises from a local spread of activity into immediately
adjacent cortex. The source is layer four and the sink is


Weeks post DC-lesion
Percent Successful Grasps
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128


part by the extent to which the spared spinal pathways
followed 10 pps. There also was an increase in the
amplitude of the 90 ms peak during the weeks following the
lesion that was correlated with a behavioral recovery in
grasping, suggesting a cortically mediated phenomenon.
vii


I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
7Vi A -
David M. Green
Graduate Research Professor of
Psychology
I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
Richard Johnson
Associate Professor of Veterinary
Medicine


Figure 3-13. The averaged pre-lesion evoked potential
recorded over SI cortex in response to electrocutaneous
stimulation of the ankle (monkey C). Solid line
represents average of responses to 320 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.


Amplitude (uV) Amplitude (uV)
109
time (ms)
ankle stimulation


157
It is possible that interruption of the DCs produces a
substantial loss of RA input and also disrupts the coding of
static skin displacement resulting from a substantial
deafferentation of cells in the DC nuclei that receive input
from SA fiber types. That is, a combination of effects may
be required to account for the finding that patients with DC
lesions have difficulty perceiving static pressure (Nathan
et al., 1986). Similarly, one monkey, in preliminary
experiments, has shown a 10-15 dB threshold shift on a
detection task in which the stimulus probe was in contact
with the skin between the delivery of 10 ms indentations for
detection (Friedman and Vierck, unpublished observations).
If one assumes that the nervous system summates the
inputs from SA and RA fibers to detect each pulse, these
results indicate that input from both RA and SA afferents is
affected by a DC lesion. However, detection thresholds for
touch of the foot are not elevated by DC interruption when
the skin is not contacted between trials (Vierck, 1977).
This result indicates that elevation of touch threshold
depends upon testing situations such as constant contact,
which in generally associated with activation of SA
afferents. However, prolonged contact with an object
invariably is associated with small movements of the skin
relative to the object, providing a repetitive sequence of
phasic tactile stimuli. In the context of the demonstration
in the present study, in which frequency-dependent


Figure 4-1. The effect of a unilateral DC lesion on
pedal grasping. Average performance of two monkeys (S
and C) on grasping food items with their feet is shown
before the lesion (weeks -8 to -1) and after the lesion
(weeks 1-7). (TOP) Performance with the DC-
deaf ferented foot. (Bottom) Performance with the foot
spared of the lesion.


CHAPTER 2
RECORDINGS FROM THE WHITE MATTER TRACTS OF THE SPINAL CORD
Following a DC lesion, the remaining pathways that
contribute to perception are the DL and AL tracts (Vierck,
1984). Where there is a deficit in an animal's behavior
following such a lesion, there must also be a deficiency in
the capacity of the spared pathways to carry the neural
information necessary for the animal to perform the task.
For example, interruption of the DC pathway leads to
deficits in frequency discrimination at frequencies above 10
pps and in duration discrimination for trains of pulses at
10 pps (Vierck et al., 1985; 1990). Thus, it is likely that
the spared pathways can not reliably carry these kinds of
information at frequencies of 10 pps or greater.
There is reason to believe that the spared pathways
emanating from the dorsal horn grey matter are subject to
modulatory influences. For example, cutaneous stimuli
suppress the responses to stimuli less than 100 ms later in
the dorsal horn (Wall, 1958). In addition, Jimenez et al.
(1987) have demonstrated presynaptic influences originating
in the brainstem and terminating on primary afferents
entering the dorsal horn. Thus, either one of these
15


EFFECTS OF A DORSAL COLUMN LESION ON SOMATOSENSORY EVOKED
POTENTIALS IN PRIMATES
By
JAMES C. MAKOUS
A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN
PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF DOCTOR OF PHILOSOPHY
UNIVERSITY OF FLORIDA
1993

ACKNOWLEDGMENTS
I would like to thank my advisor, Charles Vierck, for
taking me into his laboratory at such a late stage in my
graduate education and for his patience and support of my
sometimes unorthodox ideas and experiments. I also thank
the members of my ever-changing committee, David Green,
Bruce Hunter, Richard Johnson, Christiana Leonard, Louis
Ritz and Barry Whitsel, for their critical evaluation and
support of my research. I thank William Luttge for his many
hours spent in making this a better department, John
Middlebrooks for his support during the early stages of my
training and the Center for Neurobiological Sciences for
financial support.
I would also like to thank Jean Kaufman for teaching me
to handle and care for monkeys; Anwarul Azam for keeping the
computers on-line; Carol Martin-Elkins for teaching me basic
histology. I thank Laura Kasper, James Murphy, Anita Puente
and Karl Vierck for technical expertise. I also thank
Robert Friedman, Diana Glendinning and Douglas Swanson for
their support, advice and camaraderie during all the stages
of my education. I am especially indebted to Robert
Friedman for his generosity in sharing his time, knowledge,
ii

laboratory space and equipment all of which were in short
supply (save for his knowledge). I also thank Babbette
Botchin and Dan Thiel for expert veterinary care.
Last, I would like to thank my family; my father whose
advice both personal and professional has never steered me
wrong; and my wife, Elizabeth, who has been an endless
source of love, support and inspiration during these years
of training.
iii

TABLE OF CONTENTS
Page
ACKNOWLEDGEMENTS ii
ABSTRACT v
CHAPTERS
1 GENERAL INTRODUCTION 1
Behavior 2
Anatomy and Physiology 3
Plasticity 10
Evoked Potentials 12
Overview of Dissertation 13
2 RECORDINGS FROM THE WHITE MATTER TRACTS
OF THE SPINAL CORD 15
Methods 16
Results 22
Discussion 38
3 RECORDINGS FROM THE CEREBRAL CORTEX 42
Methods 44
Results 54
Discussion 112
4 PHYSIOLOGICAL CHANGES DURING RECOVERY FROM
A DORSAL COLUMN LESION 119
Methods 120
Results 123
Discussion 150
5 GENERAL DISCUSSION 155
Neural Mechanisms 155
Conclusions 163
REFERENCES 164
BIOGRAPHICAL SKETCH 171
iv

Abstract of Dissertation Presented to the Graduate School of
the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy
EFFECTS OF A DORSAL COLUMN LESION ON SOMATOSENSORY EVOKED
POTENTIALS IN PRIMATES
By
James Carl Makous
May 1993
Chairperson: Charles J. Vierck, Jr.
Major Department: Neuroscience
A dorsal column (DC) lesion has a significant lasting
effect on behavioral tasks that require temporal processing
of tactile information (i.e. frequency and duration
discrimination). These experiments describe physiological
correlates of the behavioral deficits in temporal
discrimination observed in primates following DC lesions.
In experiment 1, compound action potentials were
recorded from the major ascending white matter tracts of the
cord. These experiments determined the extent to which
different sensory pathways of the spinal cord responded to
high frequency stimulation. At 10 pulses per second (pps)
v

pathways in the lateral spinal columns were suppressed to
70-80% of their control values, whereas the DCs were not
suppressed at the same frequency.
In experiment 2, epidural evoked potentials were
recorded from implanted electrodes before and after a DC
lesion. In response to mechanical stimulation, the cortical
evoked potential at 10 pps could not be distinguished from
the background activity (noise) following the DC lesion.
The response to electrocutaneous stimulation showed a
frequency-dependent suppression at 10 pps, after the lesion,
that approximated a 20% reduction in amplitude.
In experiment 3, the cortical evoked potential was
monitored over weeks following the lesion. Under some
conditions, there was a significant increase in the
amplitude of a late (90 ms) peak following the DC lesion.
This increase was correlated with behavioral recovery on a
grasping task. There was no significant recovery for the
early peaks (20 and 50 ms).
In summary, a DC lesion caused an overall decrease in
amplitude of the cortical evoked potential. There was a
significantly greater frequency-dependent suppression of
responses to electrocutaneous stimulation at 10 pps
following the DC lesion. The reduction could be explained in
vi

part by the extent to which the spared spinal pathways
followed 10 pps. There also was an increase in the
amplitude of the 90 ms peak during the weeks following the
lesion that was correlated with a behavioral recovery in
grasping, suggesting a cortically mediated phenomenon.
vii

CHAPTER 1
GENERAL INTRODUCTION
Since the early 1900s investigators have attempted to
use clinical findings in patients with compromised dorsal
columns (DC) to infer the role of this pathway in
perception. These observations suggested that a lesion of
the DCs affects the ability of a patient to detect and
discriminate among a variety of tactile stimuli (see Nathan
et al., 1986). However, for most of these patients, the
lesion involved other spinal pathways as well. In other
instances, most or all of the deficits appeared to recover
over time. Nevertheless, there are deficits that are common
to most accounts of DC interruption, and these are related
to processes that required temporal processing of
somesthetic stimuli. For example, tactile direction
sensitivity or the ability to identify letters written on
the hand (graphesthesia) can be affected by such a lesion.
Graphesthesia requires the patient to integrate the stimulus
over a few seconds. It also has been reported that a
repeated tapping stimulus or an object placed in the
patient's hand will fade over time. However, there are
differing accounts with respect to absolute threshold shifts
1

2
in response to light tactile stimuli and with respect to
recovery from these deficits.
Behavior
Given the ambiguities in the clinical findings,
investigators have attempted to quantify sensory capacities
in animal models, where a lesion can be isolated to an
individual pathway and confirmed histologically. Vierck
(1977), using Von Frey hair stimulation, showed that there
was no threshold shift on the sole of the foot following a
mid-thoracic DC lesion. For a variety of other tasks,
considerable recovery of function has been observed
following a DC lesion. DeVito and colleagues (1964) found
that monkeys had only a transient deficit in weight
discrimination, and Vierck (1966) found no permanent effect
on limb position sense. Levitt and Schwartzman (1966) showed
a transient deficit in two-point discrimination;
discriminations of size and location of tactile stimuli also
recover (Vierck, 1973; Vierck et al., 1983, 1988). For many
years there was no firm evidence of any permanent sensory
deficit following interruption of the DCs. In fact, Wall
(1970, p. 518) was so bold as to say that the DCs are only
'involved in controlling the analysis of messages arriving
over the other somatosensory pathways.'
More recently, tasks that require some degree of
temporal resolution have shown long lasting sensory deficits

3
in monkeys. Vierck (1974) showed that tactile direction
discrimination was hampered for up to 1 year following a DC
lesion, whereas simple detection of movement across the skin
showed only a transient deficit. Later, Vierck et al.
(1985) showed that monkeys trained to discriminate a 10 Hz
tactile stimulus from a 14 Hz stimulus could not
discriminate 10 Hz from 35 Hz following interruption of the
DC pathway, even after extensive retraining (1 yr). Animals
trained on the same task with lesions of the dorsal-lateral
(DL) and/or antero-lateral (AL) columns showed no such
lasting deficit. In a more recent study (Vierck et al.,
1990), normal monkeys could discriminate between stimulus
trains of 3 pulses (at 10 Hz; 200 ms total duration) from
trains of 5 to 7 pulses (400-600 ms duration); however,
following interruption of the DC pathway, the animals could
not discriminate trains of 3 pulses from trains of as many
as 35 pulses. Thus, it appears that tasks requiring
temporal processing of tactile input, at least in a range of
frequencies from 10-35 Hz, depend uniquely upon input from
the DC.
Anatomy and Physiology
When the DCs are compromised, somatosensory information
reaching the cortex must be carried by the remaining
pathways. The only other spinal pathways that are thought
to contribute significantly to perception are long

4
somatosensory pathways (long tracts) in the dorsal-lateral
(DL), and antero-lateral (AL) columns (Vierck, 1984). Long
tracts in the DL column ascend the spinal cord ipsilateral
to the primary afferent fibers (Rustioni et al., 1979),
whereas the AL tract fibers cross the midline near the root
entry level and ascend the spinal cord in the
antero(ventral)-lateral quadrant of the spinal cord,
contralateral to the primary afferent fibers (Trevino and
Carstens, 1975).
The majority of the fibers constituting the DL and AL
pathways have their cell bodies in the dorsal horn, where
there are a number of modulatory influences. For example,
Jimenez et al. (1987) have shown that there are descending
fibers originating in the brainstem reticular formation and
red nucleus that have presynaptic inputs onto cutaneous
primary afferents entering the dorsal horn. Furthermore,
cutaneous information is carried up the cord to the
reticular formation (Salibi et al., 1980) and the red
nucleus (Berkley, 1986) via the DC nuclei. Therefore, a DC
lesion could result in a change in the regulation of
information entering the dorsal horn, owing to a loss of DC
connections with the reticular formation and red nucleus.
There is also evidence that primary afferents synapsing
in the dorsal horn are directly inhibited by cutaneous
stimulation (Wall, 1958; Janig, 1968). For example,
following cutaneous stimulation, there is an inhibition of

5
primary afferents in the dorsal horn lasting greater that
100 ms; however, primary afferents in the DCs show an
inhibition lasting only 25-35 ms (Wall, 1958). Therefore,
since normal neuronal excitability in the dorsal horn can
have a refractory period of more than 100 ms, it is possible
that changes in perception following interruption of the DC
results from a restriction of temporal processing of
cutaneous information in pathways emanating from the spinal
grey matter.
If pathways other than the DCs are to code for touch,
it is important that the pathways arising from the dorsal
horn carry information about non-noxious, natural cutaneous
stimuli as opposed to information strictly from muscle
afferents. Indeed, a number of studies have shown that the
AL and DL tract fibers respond to natural stimulation of the
skin (Willis et al.,1974; 1975; Surmeier et al., 1988;
Downie et al., 1988) and that they contribute to cortical
responses (Andersson et al., 1975). However, few studies
have looked at frequency coding in the AL tract; the stimuli
used in these studies usually involved a static displacement
of the skin or hair.
The DL tract has been studied much less extensively in
the primate than in the cat, and the two species appear to
differ substantially in the size of the DL pathway
(Nijensohn and Kerr, 1975). Thus, the information carried
in this pathway in primates is not well characterized.

6
However, it has been demonstrated in acute monkey
preparations that an SI cortical evoked potential is smaller
in amplitude but still intact (Andersson et al., 1972)
following interruption of the ipsilateral (to the stimulus)
DCs and the contralateral AL tract, sparing only the
ipsilateral DL tract. This result was obtained in response
to light mechanical stimulation of the skin. Although it is
still not clear the extent to which the DL and AL pathways
carry temporal information, it is apparent that both
pathways carry information that is cutaneous in nature.
The DC, DL and AL tracts synapse in the thalamus before
tactile information is transmitted to the cortex, where it
contributes to normal perception. All three long tracts
have converging inputs onto the ventro-basal complex of the
thalamus (Berkley, 1980; 1983), providing sites for
interaction among the various pathways. Indeed, a number of
studies have demonstrated the existence of excitatory and
inhibitory interaction in the ventro-basal complex of the
thalamus (Anderson et al., 1964; Janig et al., 1979; Salt,
1989). These interactions can last from 50 to 500 ms,
depending upon the cells, and are thought to shape the
spatio-temporal profile of responses that are sent to the
cortex. Thus, removal of one of the inputs to this region
(e.g., a DC lesion) could lead to an imbalance between the
remaining excitatory and inhibitory inputs. This could
change neuronal integration (filtering) in the thalamus,

7
which, in turn, could result in a change in perception.
A number of studies have attempted to ascertain the
role of the various spinal cord pathways in generating a
cortical response through evoked potential measurements. In
general the results have been inconclusive, owing to the
variety of stimuli used, the lack of repeated measures
within individual animals, and the different kinds of
anesthesia.
Gardner and Morin (1953; 1957) showed in pentobarbital
anesthetized monkeys that neither chronic nor acute DC
section altered the latency or threshold of somatosensory
cortical evoked potentials. In this study, they used
electrical stimulation directly on dissected cutaneous and
deep nerves. It was not clear how they determined threshold
or the amplitude of stimulation. It is also possible that
direct stimulation of the nerve recruited predominantly the
large diameter fibers originating in muscle (York, 1985).
Eidelberg and Woodbury (1972) also found no change in
the amplitude or latency of the cortical evoked potential
following chronic (>4 weeks) or acute DC or dorsal quadrant
lesions in monkeys. They stimulated the radial nerve
transcutaneously at 1-3 mA under chloralose anesthesia.
Unfortunately, these results were compared to unoperated
controls rather than preoperative controls from the same
animal.
On the other hand, Andersson et al. (1972) recorded

8
evoked potentials from acute Nembutal anesthetized monkeys
and found that there was an increased latency of 4-5 ms and
a decrease in amplitude of about 25% following DC section.
There was no change in the location of maximum activity from
intradermal electrocutaneous stimulation of the foot or the
hand. In the conditions when a mechanical stimulus was
used, the animal had already received a lesion of either the
ventral quadrant or dorsal quadrant before recordings were
made. This made it difficult to ascertain the contribution
of the DCs to the mechanical response.
A more recent study by Cusick et al.(1979) in monkeys
showed, under ketamine anesthesia, that acute DC section
almost completely eliminated the cortical evoked response to
exposed sciatic nerve stimulation. Following a 4-7 week
period after the lesion, there was a small increase in the
amplitude to about 25% of the preoperative control
amplitude. On the other hand, following a lesion of the DL
and AL pathways, sparing the DCs, there was no appreciable
attenuation of the evoked potential. Thus, the conclusion
from these studies is that the DCs provide sufficient input
to support a cortical evoked potential, but intact DCs are
not necessary for the presence of an evoked potential.
A few investigators have also looked at unit responses
following interruption of the DC pathway or dorsal
hemisection. Andersson et al. (1975) found, in lightly
anesthetized (pentobarbital) monkeys, that acute dorsal

9
hemisection of the cord decreased the number of units per
cortical penetration that could be driven by peripheral
stimulation. There was also a high number of units that
were spontaneously active and were driven unreliably. The
latencies of units did not appear to be longer than control
animals, but units were more often found on the hairy than
on the glabrous skin. Although most of the units tended to
be rapidly adapting, they typically could not follow
repetitive stimulation beyond 4 Hz.
These results are in general agreement with the results
of Dreyer et al. (1974), though they differ in the details.
Dreyer et al. found, in awake monkeys with chronic (21-72
days) DC lesions, that fewer numbers of units were driven by
peripheral stimulation, and the responses were less
reliable. In contrast to Andersson et al. (1975), they
found a high proportion of neurons that responded to deep
stimulation rather than light stimulation. There was a
cortical region, corresponding primarily to the center of
the hand and foot representations in areas 3b and 1, that
was nearly devoid of responses following DC lesion, whereas
the surrounding cortical areas (3a and 2) appeared more
normal in the nature and proportion of responses.
Until now the afferents in the fasciculus gracilis (FG)
from the foot have been presented as if they were
distributed in a pattern similar to that of the fasciculus
cuneatus (FC) from the hand. However, Whitsel et al. (1972)

10
found, in recordings from fibers at cervical levels, that
fibers in the FC innervated both cutaneous and deep
structures, whereas the fibers in the FG were predominantly
cutaneous. This is in contrast to recordings made more
caudally, where the fiber types were similar for both the FC
and the FG. This suggests that there is sorting of fibers
from the FG as it ascends the spinal cord, resulting in a
projection of proprioceptive afferents to the dorsal horn
and then the DL tract (Dreyer et al., 1974). Therefore, it
is possible that a lesion of the FG would produce behavioral
effects that differ from those produced by a lesion of the
FC.
Plasticity
A number of recent findings suggest there is some
degree of plasticity in the adult nervous system (see Wall,
1988 for review). For example, the results of Merzenich et
al. (1984) have shown in recordings from anesthetized
monkeys that the cortical representation of the fingers
adjacent to an amputated finger included the region of
cortex formerly dominated by input from the missing finger.
These changes in the borders of the cortical representation
were on the order of 1-2 mm and appear to represent an
unmasking of inputs that are normally suppressed by the
anesthesia. More recently, Pons et al. (1991) found that
long term (> 12 yrs) dorsal rhizotomy (C2-T4; C = cervical;

11
T = thoracic; L = lumbar) produced large (> 1 cm) changes in
the area and location of cortex represented by the face
relative to control animals. That is, the face
representation invaded the area normally occupied by the
hand. It is not clear where the actual reorganization took
place; however, given the large shift in the cortical map, a
cortical mechanism is unlikely. A more likely locus could
be the spinal cord or thalamus, where the representations of
adjacent body parts are in closer proximity.
Rausell et al. (1992) also looked at the thalamus of
the monkeys used in the Pons et al. (1991) study. They
found a down regulation of gamma-aminobutyric-acid (GABA)
receptors in the deafferented thalamus relative to controls.
They also found changes in calcium binding proteins that are
specific for either lemniscal or nociceptive pathways.
Thus, it appears that there were long term changes in the
thalamus that accompanied the reorganization of the map at
the cortical level.
Changes in spinal cord have also been observed
following deafferentation. For example, Goldberger and
Murray (1982) observed sprouting in the cord following
dorsal rhizotomy in cats. They found an increased
projection to nucleus gracilis and to the spinal laminae
that normally received projections from the spared root.
However, there was no sprouting into areas not normally
receiving projections from the spared root. There also was

12
a tendency for areas that are topographically organized to
not receive any sprouting fibers.
Thus, it appears that neural plasticity does exist in
the adult nervous system, and it is possible that changes
following injury to the brain or spinal cord could be taking
place at many possible points along the neuraxis. It is
likely, then, that a behavioral recovery following a lesion
could reflect changes in the neural connectivity in the
spared pathways.
Evoked Potentials
Evoked potentials are the summated neural response from
a group of neurons depolarizing and/or hyperpolarizing in
synchrony. The amplitude of the evoked potential is
proportional to stimulus amplitude under some stimulus
conditions (Beck and Rosner, 1968; Franzen and Offenloch,
1969; Kulics, 1982); however, this issue has been disputed
(Uttal and Cook, 1964; Schwartz, 1976). Evoked potentials
are often used as a diagnostic tool for the integrity of the
afferent pathways (Pillay, 1984). The first positive peak
in the somatosensory cortical evoked potential is thought to
arise from the depolarization of layer four (a current
sink), whereas the current source arises from the dendrites
at the surface of the cortex. The second peak (negative)
arises from a local spread of activity into immediately
adjacent cortex. The source is layer four and the sink is

13
the cortical surface where axons are contacting dendrites.
The second positive peak is derived from a more global
spread of information to association cortices. In this
condition, the SI cortex serves as a source and the other
cortical areas serve as sinks. This late positive potential
can be recorded over a large area of cortex (Arezzo et al.,
1981; Kulics and Cauller, 1986; Emerson and Pedley, 1990;
Allison et al., 1991).
Overview of Dissertation
The following chapters describe a series of experiments
that were designed to look at the effects of a DC lesion on
somatosensory evoked responses to repetitive stimulation.
These experiments describe physiological accompaniments of
the temporal discrimination deficits observed following such
a lesion. The second chapter looks at the extent to which
compound action potentials recorded in the three long spinal
tracts follow high frequency stimulation. It was expected
that such an experiment would provide evidence concerning
the origin of any frequency-dependent suppression that might
be obtained at the cortical level in the absence of the DC
pathway. The third chapter describes changes in the evoked
cortical response and its frequency-dependent suppression
following the DC lesion. The fourth chapter follows the
evoked potential as it changes over months following the
lesion. This experiment was designed to correlate changes

14
in the cortical evoked potential with behavioral changes
observed in animals recovering from DC lesions. The last
chapter discusses some possible mechanisms for the changes
in the cortical evoked potential that accompany DC
interruption.

CHAPTER 2
RECORDINGS FROM THE WHITE MATTER TRACTS OF THE SPINAL CORD
Following a DC lesion, the remaining pathways that
contribute to perception are the DL and AL tracts (Vierck,
1984). Where there is a deficit in an animal's behavior
following such a lesion, there must also be a deficiency in
the capacity of the spared pathways to carry the neural
information necessary for the animal to perform the task.
For example, interruption of the DC pathway leads to
deficits in frequency discrimination at frequencies above 10
pps and in duration discrimination for trains of pulses at
10 pps (Vierck et al., 1985; 1990). Thus, it is likely that
the spared pathways can not reliably carry these kinds of
information at frequencies of 10 pps or greater.
There is reason to believe that the spared pathways
emanating from the dorsal horn grey matter are subject to
modulatory influences. For example, cutaneous stimuli
suppress the responses to stimuli less than 100 ms later in
the dorsal horn (Wall, 1958). In addition, Jimenez et al.
(1987) have demonstrated presynaptic influences originating
in the brainstem and terminating on primary afferents
entering the dorsal horn. Thus, either one of these
15

16
mechanisms could regulate the extent to which spared
pathways contribute to perception.
It was this line of reasoning that led to the first set
of experiments. If the pathways emanating from the dorsal
horn were dramatically suppressed at 10 pps, then the dorsal
horn could be a neural locus of the behavioral deficit
observed following DC interruption. Therefore, experiments
were undertaken to record from the white matter tracts of
the cord in response to different stimulus frequencies, and
the extent to which each pathway was suppressed by
increasing frequencies was determined.
Methods
Animals
The subjects were three female macaques (1 Macaca
arctoides and 2 Macaca nemestrina) that weighed between 4.8
and 11.4 kg. They were housed in an outdoor communal
enclosure to maximize the animals' health and psychological
well being. The animals were maintained on a diet of Purina
monkey chow, fruit and water. Prior to the acute
experiments, these animals were used in two procedures: a
behavioral study in which they received a cortical lesion of
the arcuate gyrus, and an anatomical study in which they
received an injection of HPR into the lumbrical muscles of
each hand, one week prior to the acute experiment. Two

17
months prior to the acute experiment, one animal (monkey E)
had a surgical interruption of the dorsal column on the
right side between Til and T12 (see Histology). This
procedure was conducted under sterile surgical conditions by
Dr. C. J. Vierck, Jr. (see Chapter 3 Methods for details).
Preparation. Each animal was premedicated with
intramuscular (i.m.) ketamine HCL (100 mg) and atropine
sulfate (.54 mg), given intravenous (i.v.) fluids (lactated
Ringers) and then intubated. Isoflurane anesthesia was
passed to the animal and maintained at a level of 1.5-2.5%
throughout the remainder of the experiment. Each animal's
core temperature was monitored with an esophageal
thermometer and was maintained between 37 and 38 degrees C
with a heating pad (K-pad) and warmed paraffin bags. The
back of the animal was then shaved and a rostral-caudal
incision was made over the low thoracic vertebrae. The
muscle and fascia were scraped away from the dorsum of 4 or
5 vertebrae, and 2 or 3 of the dorsal laminae were removed
with rongeurs. The underlying fat and connective tissue
were dissected away, exposing the dura mater. A rostral-
caudal slit was made in the dura, and it was reflected to
expose the pia. The cord was then bathed in warm (37
degrees C) mineral oil. The remaining two spinous processes
at the rostral and caudal extent of the exposure were then
clamped and suspended by a stereotaxic frame.
Stimulation and recording. Each foot was stimulated

18
electrocutaneously at the tibial nerve, posterior to the
medial malleolus at a current sufficient to elicit a small
twitch of the first toe (ca. 5 mA). The duration of each
pulse was 0.2 ms, and the frequency of stimulation was
varied systematically from 1.5 pulses per second (pps) to 50
pps. Stimulating electrodes consisted of silver/lead solder
molded into a small bead 4 mm in diameter. The anode and
cathode were separated by 2 cm (cathode proximal),
lubricated with sergi-lube and held in place with adhesive
pads and tape. The animal was grounded with a ring
electrode placed around each calf proximal to the
stimulating electrode.
Compound action potentials were recorded from the white
matter tracts of the spinal cord by lowering tungsten
electrodes into the cord with a X-Y-Z micro-positioner.
Tungsten electrodes were made by immersing a tungsten rod
(0.007 in. diameter) into a bath of saturated sodium nitrite
and passing an AC voltage (ca. 6 volts) between the tungsten
and a carbon rod, also in the bath. The tungsten was then
slowly removed from the bath, and, in this way, a blunt
point was etched onto the end of the electrode. The
sharpened end of the tungsten was then passed through the
back end of a glass micro-pipette. The tip of the pipette
was broken to allow about 1 cm of exposed tungsten. The
tungsten was held in place by dental wax, and the entire
exposed tip of the electrode was dipped in Insl-x

19
(insulation). The tip of the electrode was then briefly
touched against a hot soldering iron. This usually yielded
impedances in the range of 10 - 100 kohms (at 1000 Hz),
depending on the duration of contact with the hot iron.
Signals recorded in the spinal cord in response to
electrocutaneous stimulation were differentially amplified
(Bak, 10,000x) in reference to a muscle flap along the
margin of the surgical opening. The signals were digitized
(11 us, Vetter), and recorded on magnetic tape (VCR) for
off-line analysis. The signal was also filtered (3-300 Hz
pass-band) and averaged on-line (286-computer; RC
electronics software) to monitor the potential during each
recording session.
Procedure. The experimental procedure consisted of the
following. The electrode was lowered into each of the major
tracks of the cord after visualizing the dorsal root entry
zone and the midline under a dissecting microscope. For
dorsal column penetrations the electrode was positioned
sufficiently near the midline to evoke a large response to
ipsilateral stimulation of the foot without evoking a
response from the contralateral foot. Dorsal-lateral
penetrations were made slightly lateral to the dorsal root
entry zone and were shallow enough to record little or no
response from stimulation of the contralateral foot.
Antero-lateral penetrations were made slightly more lateral
and deeper than the DL penetrations, to maximize a response

20
to contralateral stimulation. These locations often
produced an ipsilateral response that was less than 40% the
amplitude of the contralateral response.
After an electrode was placed in one of the tracts by
one of the above functional definitions, a frequency series
was conducted. In the case of the DC and DL tracts the
ipsilateral foot was stimulated, whereas the contralateral
foot was stimulated for the AL recordings. These three
stimulus conditions will be referred to as stimulation of
the experimental foot, whereas stimulation of the non-
experimental foot will be referred to as stimulation of the
control foot. Each frequency series consisted of 100-150
sweeps by the averaging software over a sweep duration of 75
ms. Thus, for the higher frequencies, the animal received
more stimuli (i.e. at 1.5 Hz there was 1 stimulus/sweep and
at 50 Hz there were 3 stimuli/sweep). The stimulus sequence
was typically as follows: experimental foot (at 1.5, 2.5,
5.0, 7.5, 10, 25, 50 and then 1.5 Hz), control foot (1.5
Hz), and experimental foot (1.5 Hz).
Data analysis
The data were analyzed off-line. "Raw" evoked
potential records were read off magnetic tape, band-pass
filtered (3-300 Hz), digitized (300 us bin width) and
averaged by commercially available software (RC
electronics). The 75 ms long averages were converted into

21
ASCII files and saved on disk. ASCII files were imported
into a spreadsheet, where latencies and amplitudes could be
computed. Latency was computed from the peak of the
stimulus artifact to the peak of each distinct waveform.
The peak amplitude of the potential was computed by taking
the difference between the amplitude 6 ms after the stimulus
artifact and the amplitude at the mean latency of the peak.
The response amplitudes at each frequency were expressed as
a percentage of the amplitude of the response to stimulation
of the experimental foot at 1.5 Hz (referred to as the
standard amplitude).
Histology
At the end of each experiment the animals were given an
overdose of pentobarbital (195 mg i.v.). They were then
perfused through the heart, first with warm (37 degrees C)
phosphate buffer (7.4 pH) and heparin sulfate (1 units/L),
then with fixative (2.5% glutaraldehyde and 2.0%
paraformaldehyde). This was followed by a mixture of
fixative and 10% glycerol and then rinsed with 10% glycerol
in phosphate buffer. The spinal cord was removed from C2
down to LI; the dorsal roots were counted, and the cord was
blocked 2 levels rostral and caudal to the recording
exposure. In the animal with the DC lesion, the cord was
blocked rostral and caudal to the lesion as well. The cord
was cryo-protected in a 10% formalin and 30% sucrose (or

22
glycerol) solution for a minimum of 1 week. Transverse
sections were cut on a freezing microtome at 50 urn, mounted
on slides and let dry for a minimum of 1 day. They were
then stained (cresyl violet) and cover-slipped (Permount).
The extent of the DC lesion was drawn, and the electrode
tracks were reconstructed.
Results
Histology
The locations of the recording electrodes were verified
histologically in all recordings. Each of the recording
sites for each animal is shown in Figure 2-1. The DC
recordings were typically near the midline and in the
ventral half of the DCs. In one animal (monkey K), the
recording site bordered the grey matter. The DL recordings
were usually confined to the DL quadrant but occasionally
bordered the ventral quadrant of the cord. The AL
recordings were usually ventral to, but occasionally
bordered, the DL quadrant. During the AL recordings it was
often difficult to eliminate the response from the control
foot, especially at 11 ms.
The DC lesion in monkey E was between Til and T12 and
is shown in Figure 2-2. There was complete interruption of
the right DC at this level. There was very little
involvement of the left DC or the grey matter and no
encroachment into the right DL.

23
Spinal Recordings
Table 2-1 shows the peak latencies obtained for each
animal in each tract, averaged across all frequencies. The
'n' column corresponds to the number of frequency series
that were conducted in that tract for that animal. Monkey E
received a right DC lesion more than 2 months prior to the
recordings. Note that the AL response had two peaks that
differed in latency by 3 ms in two of the three animals.
There was a tendency for potentials evoked in the post-
synaptic pathways to have a slightly longer latency (0.3 - 4
ms) than the DC pathway.
Representative averaged responses from each tract are
shown in Figures 2-3, 2-4 and 2-5. These were derived from
one animal (Monkey D) on three separate penetrations. The
response from the DC (Figure 2-3) had a latency of 9.6 ms
and showed little suppression with high frequency
stimulation. There was almost no DC response from the
control foot. The response from the DL tract (Figure 2-4)
had a latency around 10.1 ms, but showed a more pronounced
suppression with increasing frequencies. At 50 pps the
potential was little more than 50% of the standard response
to 1.5 pps. The response from the control foot was small.
The AL tract had the most complex response (Figure 2-5).
The pll response was suppressed to nearly 50% at 10 pps,
whereas the pl4 response was not substantially suppressed
until 25 pps. However, the pl4 was completely abolished at

Figure 2-1. Electrode recording locations from the
spinal cord white matter of three monkeys. All
recording sites are drawn on a standard mid-thoracic
(T8) section. Black ovals represent approximate
recording locations, while dashed lines connect
recordings sites within one electrode penetration.
Often, two frequency series were recorded at the
electrode location. Abbreviations as in text.

25

Figure 2-2. Reconstruction of the DC lesion for one monkey E. The
drawing was made from a projection of the stained spinal cord section.
The cross-hatched area represents the extent of the thoracic lesion
(T12).

to

Table 2-1. Latencies of evoked potentials and number of recordings from each subdivision of the
spinal cord. The latencies are listed for each animal in ms (re: stimulus artifact), and ’n’ corresponds
to the number of frequency series that were obtained at each site for each animal. Monkey E had a
left DC lesion 2 months prior to the recordings (see Figure 2-2), and therefore no recordings were
made from this DC tract in this animal.
monkey
DC
(ms)
n
DL
(ms)
n
AL p11
(ms)
n
AL p14
(ms)
n
E
11.4
3.0
10.8
4.0
10.9
3.0
13.1
3.0
D
9.6
2.0
10.1
5.0
10.6
5.0
13.9
5.0
K
9.9
3.0
11.0
4.0
-
-
15.3
1.0
ave
10.3
10.7
10.8
14.1
std
1.0
0.5
0.2
1.1

Figure 2-3. Compound action potentials recorded from
the DC of monkey D. (TOP) The responses to different
frequencies of ipsilateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the contralateral (control) foot at 1.5
pps expressed as percentage of the ipsilateral response
at 1.5 pps.

30
Spinal cord recordings
dorsal column
0 5 10 15 20
time (ms)

Figure 2-4. Compound action potential recordings from
the DL tract of monkey D. (TOP) Responses to different
frequencies of ipsilateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the contralateral foot at 1.5 pps.

32
Spinal cord recordings
dorsal-lateral
0-
r
/
v /
/ N
y ^ y
y
control
foot
-20-
i r
10
-i—i—i—i—i—i—i—i—i—i
15
20
time (ms)
o
t 1 1 r
5

Figure 2-5. Compound action potentials recorded from
the AL tract of monkey D. (TOP) Responses to different
frequencies of contralateral stimulation of the tibial
nerve are shown and are expressed as a percentage of
the response to 1.5 pps. (BOTTOM) The response to
stimulation of the ipsilateral foot at 1.5 pps.

34
Spinal cord recordings
antero —lateral
20-
0-+
0
-\
t 1 r
r-6 i 1 1 1 1 1 1 1 1 r
5 10 15
time (ms)
control
- foot
T
20

Figure 2-6. Responses obtained from each subdivision of the spinal
cord, averaged across animals. Amplitudes are expressed as a percentage
of the response to 1.5 pps. Error bars represent + 1 SE. The SEs for
the AL, pl4 response were omitted for clarity and ranged from about 5%
to about 20% depending on the stimulus freguency. The points shown in
the lower left of the Figure represent responses to stimulation of the
control foot for each subdivision.

Amplitude ($ control: 1.5 pps)
dorsal column
dorsal-lateral
antero—lateral
antero—lateral

37
50 pps, whereas the pll was not. Moreover, the pl4 appeared
to shift its latency at 25 pps, which suggests the existence
of yet a third peak that was unmasked at 25 pps. Both
animals with a pl4 response exhibited this phenomenon. The
pll response from the control foot was 20% of the standard
response to stimulation of the experimental foot, which was
not uncommon for this electrode location.
Averaged (across animals) frequency-response functions
for each of the tracts are shown in Figure 2-6. The most
obvious result was that responses from the DL and AL columns
did not follow the 50 pps stimulus as well as the potentials
within the DC pathway. However, at 10 pps the late response
from the AL tract (p14) was not significantly different from
the DC response. In fact, there was even a slight (but not
significant) augmentation of the pl4 response at 2.5 pps.
Beyond 10 pps, however, there was a precipitous drop off in
the response at pl4 to higher frequencies. The AL response
at pll showed a similar trend to the response from the DL
tract at the low frequencies, but beyond 10 pps the two
functions diverged. The DL response was never suppressed to
more than 70% of control at the highest frequencies, whereas
the pll response from the AL tract at 50 pps was down to 20%
of the standard amplitude.
Summary
In response to electrocutaneous stimulation of the

38
tibial nerve, the DC pathway showed a significantly (p<0.05)
smaller suppression than any other subdivision of the spinal
cord, at stimulus frequencies of greater than 10 pps. At 10
pps or less, the three tracts were suppressed by nearly
comparable amounts. At 10 pps, suppression of the pl4
response from the AL tract was not significantly different
than the DC suppression. On the other hand, the DL and the
AL (p11) responses were significantly (p<0.05) more
attenuated at 10 pps than the DC response.
Discussion
The principal result of this study was the observation
that ascending pathways in the lateral columns, which
emanated from the dorsal horn, are not profoundly suppressed
by repetition rates up to 10 pps. Therefore, behavioral
deficits in detection of 10 pps stimulation after
interruption of the dorsal columns are unlikely to be
attributed to a suppression of input to supraspinal targets
of pathways in the DL and AL tracts. At 10 pps, where the
tracts respond at 70% of the standard response or greater,
it is possible that any one of the pathways could contribute
significantly to the perception of a 10 pps stimulus.
Latency
The relative latencies of responses within the three

39
tracts was as expected. The DC pathway had the shortest
latency to peak (10.3 ms), whereas the DL and AL had longer
latencies (10.7 and 10.8 ms, respectively). Since these
latter two pathways comprise post-synaptic populations of
fibers and do not include primary afferents (in contrast to
the DC), it follows that longer latency responses were
obtained from the lateral columns. The AL and DL responses
should be nearly 1 ms later than responses from the DC,
given the mandatory synapse (i.e. delay of 1 ms) in the
dorsal horn. It is possible that a combination of factors
contributed the 0.5 ms difference actually observed. For
one, the DC response from monkey E was about 1.5 ms longer
than the DC response from the other two animals. Since the
DCs also have a large number of post-synaptic cells arising
from the dorsal horn (Rustioni et al., 1979), it is possible
that this recording was made from a division of the DC with
a preponderance of post-synaptic fibers. Since there was a
DC lesion in monkey E on the contralateral side, responses
arising from the control foot were not a determining factor
for this electrode placement, as it could have been in the
other recordings. Another factor that could have
contributed to the small difference between the DC and AL
latencies was the large bin width of 0.3 ms.
In addition to peaks at 11 and 14 ms, there was a peak
at 15 ms that appeared only at 25 pps in the AL response,
but it was abolished at 50 pps. It is possible that this

40
peak was derived from a third group of fibers in the AL,
given its different latency and unique frequency
sensitivity.
One animal (monkey K) showed no appreciable pll
response in the AL tract. It is not clear why this
occurred, since the recording electrode in this animal did
not appear to be in a substantially different location than
the other two animals. It is possible that the high
electrode impedance (100 kohms) used in this animal drew
from a smaller population of fibers than the electrodes used
in the other two animals (15 and 65 kohms).
Frequency Response
The DC response showed less suppression than the other
two tracts at all frequencies above 10 pps. This result was
not unexpected since the DL and AL tracts do not contain
primary afferent fibers. Because each synaptic delay tends
to decrease the reliability of high frequency transmission,
the DC should be better equipped to carry high frequency
information up the cord. Conversely, one could argue that
the AL and DL tracts do carry high frequency information,
but it is lost in the averaged response, owing to a variable
latency of individual responses. If this were the case, one
would expect to see not only a decrease in the amplitude of
the response at high frequencies, but also a broadening of
the peak at high frequencies. This was not observed in
either the DL or the AL tracts.

41
Summary
These experiments demonstrated, through compound action
potentials recordings from large populations of spinal
fibers, that the extent of suppression for the different
pathways at 10 pps is similar. In the most extreme case,
the AL pll response was 70% of standard amplitude in
contrast to no suppression for the DC response (100% of
standard). Thus, it is likely that the pathways spared of a
DC lesion could reliably carry 10 pps stimulus up the cord.
However, at 50 pps there were large differences in the
frequency-dependent suppression of different pathways.
If any of the long spinal tracts were to be compromised
in some way (i.e. by a lesion), it is possible that, at the
cortex, there would be a decreased response amplitude,
because some percentage of the input to cortex was lost. It
is also possible, given the small difference (ca. 20%) in
slope between the DC and other pathways, that there would be
a concomitant change in slope of the frequency-response
function at the cortex following a DC lesion. If these were
indeed the outcomes of cortical recordings, then the animal
in a behavioral task might require a larger stimulus for
detection and could reveal an alteration in threshold with
stimulation frequency.

CHAPTER 3
RECORDINGS FROM THE CEREBRAL CORTEX
Following a DC lesion, the information arriving at the
cortex is limited by the extent to which the spared pathways
(DL and AL) carry somatosensory information and by the
responsivity of partially deafferented central relays of the
spared input. Since there are behavioral deficits in
discrimination of repetitive stimulation at frequencies of
10 pps and above, it should be instructive to look at
cortical responses to 10 pps before and after a DC lesion.
There are several possible outcomes of these recordings:
1) It is possible that, following a DC lesion, the
cortical evoked potential is diminished in amplitude.
Although this has been the subject of some dispute (see
Chapter 1), it is likely that a removal of one of the long
tracts would result in the diminution of the overall amount
of input to cortex. This result would suggest that an
elevation of detection thresholds could be seen following
the lesion. However, this has not been found with
application of von Frey hairs to the sole of the foot
(Vierck, 1977) or with brush stimuli to the lateral calf
(Vierck, 1974). Thus, it appears that input from infrequent
42

43
stimulation (e.g., von Frey hairs or brush stimuli) gains
access to the cortex more effectively than input which has
been preceded by recent stimulation (e.g., train of pulses).
2) It is possible that, following a DC lesion, there
is a change in the extent to which the entire cortical
evoked potential is suppressed by increasing frequency.
This result would suggest that information transmitted to
the cortex over the spared pathways is compromised by the
capacity for these alternate pathways (or partially
deafferented relays) to follow a 10 pps stimulus. Such a
frequency-dependent suppression of early and late peaks
would suggest that the locus of the effect is sub-cortical:
either at the dorsal horn or thalamus.
3) It is possible that, following the lesion,
different peaks in the cortical evoked potential would be
suppressed by different amounts, either in absolute
amplitude or in frequency-dependent suppression. For
example, it is possible that the first peak of the evoked
potential, which is associated with the depolarization of
layer four, would show no change in amplitude or frequency-
dependent suppression. If only the later peaks, associated
with the spread of information that arose from layer four,
showed an effect of the lesion, this would suggest that the
pathways spared by the lesion adequately carry the
information to the cortex, but that there are changes at the
cortical level following deafferentation that affect the

44
animal's ability to perform the task.
The above reasoning led to the experiments below. The
idea was to determine changes in the cortical evoked
potential following a DC lesion. In this way, the neural
mechanisms underlying the behavioral deficit might be
ascertained.
Methods
Chronic Recordings
Subjects and Training. The subjects were three female
Macaca arctoides (stumptailed macaques) that weighed between
8.6 and 11.3 kg. These animals were not used in the acute
spinal cord experiments. The animals were housed in an
outdoor communal enclosure to maximize their health and
psychological well being. They were tested five or six days
a week. Each day the animals were led into the laboratory
on a leash and seated comfortably in a plexiglás primate
chair. They were gradually trained to tolerate gentle
restraint of their wrists and ankles by leather straps. In
the chair, apple sauce was dispensed through a tube in
response to the animal pressing a bar. After 10-15 min in
the chair, each animal was returned to its home "run" for
the normal diet of Purina monkey chow, fruit and water (ad
libitum).

45
Surgery. Following chair training, epidural recording
electrodes were implanted over primary somatosensory cortex
(SI). This was done under sterile conditions at the
University of Florida animal surgery facility. The animals
were premedicated with ketamine HCL (100 mg) and atropine
sulfate (0.54 mg) before intubation; then Halothane
anesthesia was administered and maintained at 1.5-2.0%.
During the implantation, the skull was exposed, the
bone was cleared of muscle and fascia, and 10 surgical
grade, stainless steel bone screws were implanted. Five
screws were placed over each SI foot representation, in 3-4
mm increments along (3 mm lateral to) the midline (see
Figure 3-1). The stereotaxic coordinates were chosen so as
to cover and flank the foot representation on each side.
Two or four reference electrodes were also implanted over
each frontal lobe. A teflon coated platinum-iridium wire
(Medwire) was passed from the head of each screw to a
miniature D-25 connector that was encased in dental acrylic,
along with the implanted screws. The skin flaps were closed
to cover the skull not covered by acrylic. The animals were
given antibiotics (Dualpen, i.m.) for 1 week following the
surgery and Torbutrol (0.5mg/6hrs) for pain.
Another surgery was performed after normal (pre-lesion)
evoked potential recordings were collected from each animal
(typically for 2 months post-implant). During this surgery,
a unilateral fasciculus gracilis lesion was made by Dr. C.J.

46
Vierck, Jr. (sponsor) at a mid-thoracic level. A
laminectomy was performed on 2 mid-thoracic vertebrae; the
dura was pulled aside, and the dorsal cord was exposed. The
cord was visualized with a microscope, and the dorsal white
matter was interrupted with precision forceps between the
midline and the root entry zone on one side. The incision
was closed, and each animal was given antibiotics (Dualpen,
i.m.) for 1 week following the surgery.
Recording. The animals were seated in a primate chair
that provided loose restraint of the arms, legs and abdomen.
The male D-25 connector on the head was mated with a female
D-25. The female connector was connected, via individually
shielded cables, to a manual switch box located on the wall
adjacent to the animal. The switch box allowed a choice
between any reference electrode, located over frontal
cortex, and any "active" electrode over SI cortex. The two
outputs from the switch box were differentially amplified
(Bak; 10,000x), digitized (Vetter), and recorded on magnetic
tape (VCR) for off-line analysis. The signal was also
averaged on-line (286-computer; RC electronics software) to
monitor the evoked potential during each recording session.
Stimulation. While in the primate chair, the sole of
each foot was stimulated either electrocutaneously or
mechanically. An S88 stimulator (Grass) generated the
stimuli. The stimulus frequencies typically ranged from 1.5

47
pps to 10 pps for both electrocutaneous and mechanical
stimuli. The number of presentations of each stimulus
condition varied from 64-320, depending upon the stimulus
frequency.
For the electrocutaneous stimuli, the output of the S88
passed through a stimulus isolation unit, a constant current
unit, a current monitor, and then out to the animal. Each
animal received stimulation of the foot via two wells in
adhesive foam pads that were filled with either Sergi-lube
or electrode paste. The amplitude of stimulation (4 mA) was
chosen so as to elicit a recognizable evoked potential
without causing any discomfort to the animals or a
perceptible muscle twitch. The duration was short (0.2 ms)
to minimize the stimulus artifact. Two animals received
electrocutaneous stimulation of the ankle with ring
electrodes made of aluminum foil. Each 3/4 in. strip of
foil was coated on one side with sergi-lube, wrapped around
the ankle or the calf, and held in place with adhesive tape.
Stimulus amplitude was 12 mA, which caused a slight twitch
of the foot during about half of the recording sessions.
Mechanical stimulation was provided by a vibrator (Ling
102) that was driven by a locally designed and constructed
driver that took the voltage output of the S88 (a 10 ms
pulse) and matched it to the current requirements of the
vibrator. The vibrator was mounted on a track that could be
vertically advanced by turning a screw with a 1 mm pitch. A

48
9 nun diameter probe, mounted on the end of the vibrator,
passed up through a linear voltage displacement transducer
(LVDT; Schaevitz) and then through a 1.9 cm hole drilled in
a plexiglass foot rest. The monkey's foot was held in place
by a polyform cast, such that the thenar eminence of the
foot was directly over the 1.9 cm hole. The probe was
advanced to make a 1-2 mm indentation in the skin. The
stimulus amplitude was calibrated to 0.4 mm, monitored
(LVDT) throughout each session on an oscilloscope, and saved
on magnetic tape.
Data analysis. All data were analyzed off-line. The
"raw" evoked potential records were read off tape, low-pass
filtered (100 Hz), and digitized (1000 Hz, 1 ms bin width)
by commercially available software and an A-D board (RC
Electronics). The digitized records were converted into
ASCII files for further analysis by software written in 'C
(by the author).
The averaged evoked potentials were constructed first
by discarding any traces that fell outside of a user
specified amplitude window (typically + 300 uV). This was
intended to reject evoked potentials that contained movement
artifact. The remaining traces from an individual session
were then averaged, and the standard deviation (SD) was
computed for each time point (bin) in the average. Averaged
data from individual days were combined into averages across

49
blocks of days with similar stimulus conditions, and
comparisons between pre-lesion and post-lesion data were
based upon these blocked averages. To compare the evoked
potentials recorded under different conditions, the peak-to-
peak amplitudes of p20-to-n50 and n50-to-p90 were computed
(see Figure 3-3). This was done to avoid problems presented
by a fluctuating baseline, especially at different stimulus
frequencies and after the DC lesion, when baseline
fluctuations approached the amplitude of the evoked
potential.
Estimates of baseline levels of noise were made by
calculating the mean amplitude and variance of the
recordings obtained during the 250 ms before each stimulus
onset at 1.5 pps. This was done by taking a random sample
of 1 ms bins. Each sample was taken from a 10 ms window,
once every 20 ms. This procedure yielded results that did
not differ significantly (p<0.05) from sampling once every
50 ms (at 50 ms the autocorrelation function was zero).
However, this technique provided a better estimate of the
noise by increasing the number of samples.
The statistical analyses were all done by programs
written in 'C by the author. A t-test was used to identify
significantly different slopes and y-intercepts (Mendenhall
et al., 1986; pg. 464) for functions relating response
amplitude to stimulus frequency. This was done first by
fitting a linear (least-squares-fit) function to the data.

50
Then, the mean and variances of the estimates of the slope
and y-intercept were used to compute the test statistic 't.'
This was a conservative test.
Acute Recordings
Animals. Acute recordings from SI cortex were obtained
from three female stumptailed macaques, two of which were
used in the awake experiments above, and three female rhesus
monkeys (Macaca mulatta). The rhesus monkeys were
previously used in behavioral experiments in vision, and had
received horseradish peroxidase injections in small muscles
of the hand and forearm one week prior to the acute
experiment.
Preparation. Each animal was premedicated with
atropine (1.0 cc), and then put into a 72 liter plastic
container that had been filled with isoflurane (about 4%).
The animal was removed once it was flaccid (about 5 mins).
It was then intubated, given isoflurane anesthesia and
intravenous fluids consisting of: lactated Ringer's, sodium
bicarbonate (1 meq/kg/6hrs), mannitol (1 g/kg), and a
corticosteroid (dexamethasone, 2 mg/kg/8hrs). Isoflurane
anesthesia was maintained at a level between 1.5-2.5%
throughout all surgical manipulations. Each animal's core
temperature was monitored with an esophageal thermometer and

51
was maintained between 37 and 38 degrees C with a heating
pad (K-pad) and warmed paraffin bags. After placement in a
stereotaxic head holding device, the head was shaved, and an
incision was made along the midline of the head. The bone
was scraped clean of tissue, and a single 1.4 cm hole was
made unilaterally over SI cortex with a trephine. Rongeurs
were used to extend the hole to the midline. The dura was
dissected away with iridectomy scissors and precision
forceps to expose the underlying pia. The cortex was then
bathed in artificial cerebral spinal fluid (CSF; Merlis,
1940).
Recording. A recording chamber was mounted over the
opening with stainless steel screws and dental acrylic. It
was filled with artificial CSF and closed-off with a device
designed to hold a recording electrode and microdrive. This
setup formed a tight seal, but it allowed the electrode to
be positioned anywhere within the chamber, while keeping
track of the x-y coordinates to within 1/4 mm. The head was
then supported by a screw imbedded in the dental acrylic on
the skull, and the ear and eye bars were removed.
Electroencephalogram (EEG) electrodes were attached to two
screws that had been threaded into the skull over the
frontal and occipital cortices. The EEG was then
differentially amplified (10,000x), filtered (low-pass 40
Hz) and displayed continuously on an oscilloscope. Once the

52
surgery was complete, and the animal's head was suspended by
the screw in the acrylic cap, the anesthetic was changed to
nitrous oxide (66%) and isoflurane 0.5-1.0% (Tigwell and
Sauter, 1992). The animal was then given a dose of
Pancuronium (0.03 mg/kg/3hrs i.v.) and put on an artificial
respirator (Harvard; 20 breaths/min; 10 ml/kg body mass).
The plane of anesthesia was monitored by the EEG, and the
expired C02 was maintained between 35 and 40 mm Hg.
Glass and Insl-x coated tungsten electrodes (impedance
= 50-200 kohms at 1000 Hz; see chapter 2 for electrode
construction) were lowered into the cortex with the
microdrive (Narishige). The electrode depth was chosen to
maximize the early negative potential (ca. 20 ms). In this
way, the recordings were always near to, but deeper than,
layer IV. Evoked potentials were differentially amplified
(10,000x), digitized (Vetter) and saved on magnetic tape
(VCR). The potentials were also filtered (3-300 Hz) and
averaged on-line (1 ms bin width; RC Electronics A-D board
and software). The averages were saved on disk in ASCII
format.
Stimulation. Electrocutaneous stimuli were delivered
to the thenar eminence and ankle of each foot. These
stimuli were similar to those described above in the Chronic
Recordings. The amplitude of the thenar stimulus was
typically 5-6 mA, whereas the ankle stimulus was 12 mA.

53
Stimulus frequencies were 1.5, 2.5, 5, 7.5, and 10 pps.
Histology. At the end of each experiment, the animal
was given an overdose of sodium pentobarbital (195 mg i.v.)
and perfused through the heart. The stumptails were
perfused with saline and 1 ml/L of heparin sulfate, and then
with 10% formalin. The rhesus monkeys were perfused first
with warmed (36 degrees C) phosphate buffer (7.4 pH) and
heparin sulfate, and then with fixative (2% paraformaldehyde
and 2.5% glutaraldehyde). This was followed by a mixture of
fixative and 10% glycerol and rinsed with 10% glycerol in
phosphate buffer. The brain and spinal cord were removed,
and the cortex was photographed. The spinal cord and cortex
were blocked and cryo-protected in 30% sucrose (or glycerol)
and 10% formalin for a minimum of 1 week. Frozen sections
were cut at 50 urn, and stained with cresyl violet. In
animals with DC lesions, the extent of the lesion in the
cord was reconstructed with camera lucida drawings.
Data Analysis. Averages were compiled on-line from
100-150 stimuli, converted to ASCII files and saved on disk
for later analysis. The data were analyzed with spreadsheet
software where peak values of n20 were computed relative to
a baseline value. The baseline was taken as the maximum
amplitude between about 10 and 15 ms after the stimulus.
For each recording location, evoked potential amplitudes

54
were expressed as percent of the response to 1.5 pps.
Results
Chronic Recordings
Histology. The locations of the recording electrodes
for the three animals are shown in Figure 3-1 (arrows). The
active electrodes were either directly over or bordered the
SI cortex in all three animals. In monkey C, the active
electrodes (indicated by arrows) were located over the
posterior half of the precentral gyrus (in the motor strip).
The electrode used to record from the DC deafferented cortex
(on the left) was actually over the midline in monkey C.
However, the potentials from the two sides of the animal
were similar in shape and latency, and these potentials were
similar to those obtained in the other animals. Therefore,
it is likely that recordings from all three animals arose
from similar sources in the cortex.
The dorsal column lesions in all three animals were
complete and are shown in Figure 3-2. Monkey F received two
consecutive lesions separated by four months. The first DC
lesion (right side) was at spinal cord level T7, included
some of the grey matter in the dorsal horn and crossed the
midline in the most dorsal part of the left DC. The second
DC lesion in monkey F was between level T3 and T4 on the
left, and it included gray matter in the dorsal horn at the

55
midline. This lesion crossed the midline to include the
dorsal aspect of the right DC, and it crossed the dorsal
root entry zone to include a small portion of the DL tract.
The DC lesion in monkey S was on the right, between T8 and
T9; it crossed the midline to include the ventro-medial
portion of the left DC, and it included dorsal grey matter
up to and including the central canal. The DC lesion in
monkey C was the largest of the three animals. It was
between T7 and T8 on the right, and it included much of the
left DC, sparing a dorsal-lateral portion. In addition,
part of the right DL tract was included in this lesion.
Mechanical stimulation. A normal epidural evoked
potential recorded over SI cortex (see Figure 3-1 for
location) in response to a mechanical displacement of the
skin (0.4 mm, 10 ms, 1.5 pps) is shown in Figure 3-3. The
solid line denotes the average response (monkey S),
accumulated from 210 stimulus presentations over 5 recording
sessions (days), and the dashed lines represent plus and
minus one standard error (SE) at each time point along that
average (1 ms bin width). The first major positive peak
occurred around 20 ms after the onset of the stimulus (see
also Table 3-la). The next two major peaks in the response
were around 50 ms and 90 ms. Although these peaks did not
always occur at exactly these latencies under all stimulus
conditions in all animals, p20, n50 and p90 will be used to

56
refer to these major peaks for ease of nomenclature.
The effects of different stimulus frequencies on the
evoked potential from normal monkeys are shown in Figure 3-
4. Stimulus frequencies ranged from 1.5 to 10 pps and are
listed to the right of each trace. The control frequency
(1.5 pps) was repeated at the end of each series to monitor
any possible changes in the response over the recording
session. In this Figure, the stimuli were averaged in
sweeps of 500 ms. At 10 pps the evoked potentials from
successive stimuli interact, since each response lasted
longer than the inter-stimulus-interval (100 ms). Following
interruption of the DC, the evoked potential in response to
mechanical stimulation was attenuated considerably, even at
1.5 pps (Figure 3-5, monkey S). At 10 pps the potential was
nearly buried in the noise. Note that the amplification
scale is the same in both Figures 3-4 and 3-5. After DC
lesions, a large attenuation of responses to all frequencies
was observed in all three animals when stimulated
mechanically.
This result is shown quantitatively for the three
animals in Figure 3-6 by expressing the amplitudes of the
p20-n50 complex (top) and p90-n50 complex (bottom) in terms
of average percents of the pre-lesion amplitude at 1.5 pps.
The pre-lesion (solid line, open triangles) frequency-
response function does not drop below 50% at 10 pps for
either complex. On the other hand, the post-lesion response

57
(long dashes, open squares) to 1.5 pps is nearly 20% of the
pre-lesion response to 1.5 pps, and the post-lesion response
to 10 pps is just above the noise (solid line = average
noise, short dashes = 95% confidence interval). For both
the p20-n50 and p90-n50 complexes there was a statistically
significant effect of the lesion on response amplitude (y-
intercept) at the p<0.01 level. Each individual animal also
showed a significant amplitude shift (see Tables 3-2 and 3-
3).
It was also of interest to determine if there was a
change in the slope of the frequency-response function with
the lesion. That is, did the lesion cause a greater
frequency-dependent suppression at 10 pps relative to 1.5
pps? This is shown quantitatively in Figure 3-7 by
expressing the amplitude of both pre- and post-lesion
complexes in terms of percent amplitude of the each response
to 1.5 pps. Neither the p20-n50 nor the p90-n50 complexes
showed a significant change in slope, as a result of the
lesion, in response to mechanical stimulation. This was
also true for individual animals (Tables 3-2 and 3-3);
however, the post-lesion potentials were limited by a floor
effect, starting with considerable attenuation of responses
to the low frequency (Figure 3-6).
Not only were responses to a mechanical stimulus
significantly suppressed at stimulus frequencies between 1.5
and 10 pps, but a similar result was obtained from one

58
animal (monkey C), with stimulation at 0.1 pps in both the
pre-lesion and post-lesion conditions. The post-lesion p20-
n50 and p90-n50 complexes were suppressed to 23.4% and 18.4%
of pre-lesion amplitudes, respectively. These results
suggests that, over a 100 fold range of stimulus
frequencies, interruption of the DCs suppressed responses to
mechanical stimulation by at least 40% at all frequencies,
and by greater than 70% at low frequencies.
Electrocutaneous Stimulation. A normal evoked
potential, recorded over SI cortex (monkey S) in response to
electrocutaneous stimulation of the foot (0.2 ms, 4 mA, 1.5
pps), is shown in Figure 3-8. This potential was recorded
from the same electrode location as the potential shown in
Figure 3-3; however, it was recorded on alternate days. The
average (solid line) and SE (dashed lines) of the response
at each time point are shown for 303 stimulus presentations
collected over five separate days. The latencies of the
different peaks were approximately the same as for the
mechanical stimulation (Table 3-lb). However, in this
figure a stimulus artifact can be seen at 0 ms.
Responses to different frequencies of electrocutaneous
stimulation are shown in Figure 3-9 for the normal cortex
and Figure 3-10 for the DC deafferented cortex. In general,
the shape of the normal evoked potential did not change
substantially in response to different stimulus frequencies,

59
except for 10 pps, where successive responses interacted.
There was also a shift in the n50 minimum to an earlier
latency at frequencies between 2.5 pps and 5 pps. The
effect of a DC lesion on the responses to electrocutaneous
stimulation was to decrease the overall amplitude, though
not to the extent seen for mechanical stimulation (shown in
Figures 3-3 and 3-4). This improvement in the post-lesion
signal-to-noise ratio provided an opportunity to examine
frequency-dependent suppression in the absence of a floor
effect, in contrast to the response from the mechanical
stimulus.
Figure 3-11 shows the effect of a DC lesion on averaged
frequency-response amplitudes, for both the p20-n50 (top)
and p90-n50 (bottom) complexes. The p20-n50 complex was
reduced in amplitude by 60% or more at all frequencies post¬
lesion relative to the pre-lesion amplitude at 1.5 pps
(p<0.01). This decrease in amplitude was also significant
(p<0.01) for the p20-n50 complex in each of the three
animals. The y-intercept was not significantly altered for
the p90-n50 complex; however, since the average function was
not linear, this was not a valid test. When the difference
between the pre-lesion mean amplitude (across frequency) and
post-lesion mean amplitude of the p90-n50 complex was tested
for significance (t-test), there was a reliable difference
between means (p<0.05). One animal (monkey S) that had a
relatively linear function showed a significant change in

60
the y-intercepts (p<0.01) of the functions relating
amplitude of the p90-n50 complex to frequency (see also
Tables 3-2 and 3-3).
The DC lesion led to an increased frequency-dependent
suppression of the p20-n50 response to electrocutaneous
stimulation of the foot (Figure 3-12, top). This effect was
not observed in the p90-n50 complex (Figure 3-12, bottom).
The slope of the frequency response function was
significantly (p<0.01) steeper in the post-lesion cortex
than the pre-lesion cortex for p20-n50. There was about a
20% greater reduction in amplitude at 10 pps following the
lesion, relative to the pre-lesion suppression by 10 pps.
This frequency-dependent suppression was true for two of the
three individual lesions (p<0.05; see Table 3-2).
Thus, the p20-n50 complex of the evoked responses to
electrocutaneous stimulation was significantly decreased in
amplitude by a DC lesion, and frequency-dependent
suppression was increased. This was also true for the p90-
n50 complex in amplitude but not for frequency-dependent
suppression.
Ankle stimulation. A normal evoked potential, recorded
over SI cortex (monkey C) in response to electrocutaneous
stimulation of the ankle (0.2 ms, 12 mA, 1.5 pps), is shown
in Figure 3-13. This potential was recorded from the
electrode location shown in Figure 3-1. The average (solid

61
line) and SE (dashed lines) of the response at each time
point are shown for 320 stimulus presentations collected
over five separate days. The latencies of the different
peaks were approximately the same as for mechanical
stimulation and electrocutaneous stimulation to the foot
(Table 3-lc). In this Figure, the stimulus artifact is a
small negative deflection at 0 ms.
Averaged responses to different frequencies of ankle
stimulation are shown in Figure 3-14 for normal cortex and
Figure 3-15 for the DC deafferented cortex. In the normal
cortex, p20 remained relatively constant with changes is
stimulus frequency, whereas p90 suppressed with increasing
frequency. Following the DC lesion, there was about a 40%
reduction in the amplitude of the p20-n50 complex at all
frequencies (Figure 3-16). After the lesion, the p90-n50
complex showed about a 50% reduction in amplitude at 1.5 pps
but only a 10-15% reduction in amplitude at 10 pps. Both
the p20-n50 and p90-n50 complexes showed a significant
(p<0.01) decrease in amplitude following the lesion. The
individual animals also showed this effect (see Tables 3-2
and 3-3).
The frequency-dependent suppression following the DC
lesion was similar to the pre-lesion condition. There was a
20-50% reduction at 10 pps relative to 1.5 pps for both
complexes (Figure 3-17). One of the animals (monkey S)
showed a significant difference in slope for the p20-n50

62
complex between the normal and the DC-deafferented cortex
(p<0.05), but this was not true for the average of the
animals. It should be noted that, in monkey S, the
comparison between the sides was made after the DC lesion;
consequently, there was a partial DC lesion on the control
side of this animal.
The evoked potential recorded in response to
electrocutaneous stimulation of the ankle showed that
interruption of the DC led to a change in the amplitude of
both the p20-n50 and p90-n50 complexes. However, there was
no significant change in the slope of either frequency-
response function following the DC lesion, in contrast to
the results from electrocutaneous stimulation of the thenar
eminence of the foot.
Summary of Chronic Recordings. The awake recordings
showed that under all stimulus conditions there was a
statistically significant change in the amplitude of the
evoked potential following interruption of the DC. When
electrocutaneous stimulation to the sole of the foot was
used, there was a significant change in the frequency-
dependent suppression of the early response after a DC
lesion. This result was not observed under conditions of
mechanical stimulation of the foot or electrical stimulation
of the ankle.

Figure 3-1. Locations of chronic recording electrodes in the three
monkeys used in the awake experiments. Arrows indicate 'active'
electrodes. The 'reference' electrode was always contralateral to and
frontal to the active one. (A = anterior; P = posterior; L = left; R =
right; CS = central sulcus; IPS = intra-parietal sulcus)

Monkey s
Monkey c

Figure 3-2. DC lesions from the three monkeys used in the chronic
recordings. Each drawing was made from a projection of the stained
spinal cord sections. The cross-hatched areas represent the extent of
each lesion.

T8-T9
Monkey F
T7
Monkey F
T3-T4

67
Table 3-1. Evoked potential latencies. Each block shows the peak latencies for each
component of the evoked potential in response to electrocutaneous, mechanical or ankle
stimulation before and after a DC lesion.
Monkey
Stimulus
Pre-les
Pre-les
Pre-les
Pst-les
Pst-les
Pst-les
/Foot
p20 (ms)
n50 (ms)
p90 (ms)
p20 (ms)
n50 (ms)
p90 (ms)
F/R
elec
21.0
48.0
96.0
23.0
48.0
93.0
F/L
elec
21.0
48.0
95.0
23.0
45.0
87.0
S/R
elec
19.5
55.0
83.0
23.0
56.0
94.0
Average
20.5
50.3
91.3
23.0
49.7
91.3
Std. Dev.
0.87
4.04
7.23
0.00
5.69
3.79
C/R
mech
23.0
58.5
85.5
25.0
46.0
92.0
F/L
mech
23.0
55.0
93.0
23.0
53.0
93.0
S/R
mech
22.0
47.0
89.5
26.0
42.0
90.0
Average
22.7
53.5
89.3
24.7
47.0
91.7
Std. Dev.
0.58
5.89
3.75
1.53
5.57
1.53
S/L*
ankle
17.0
33.0
88.0
-
-
-
S/R
ankle
-
-
-
19.0
55.0
77.0
C/R
ankle
19.0
55.0
84.0
19.0
47.0
87.0
Average
18.0
44.0
86.0
12.7
34.0
54.7
Std. Dev.
1.41
15.56
2.83
10.97
29.72
47.61
* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle
stimulation. All recordings were made (after a right DC lesion) on the control and deafferented
sides.

Table 3-2. Results of statistical comparisons between pre-lesion and post-lesion frequency-response functions for the
p20-n50 complex. Significance level is given (ns = not significant).
monkey
foot
mech
stim
slope
y-int
elect
stim
slope
y-int
ankle
stim
slope
y-int
F
R
-
-
-
+
0.05
0.01
-
-
-
F
L
+
ns
0.01
+
ns
0.01
-
-
-
S*
R
+
ns
0.01
+
0.05
0.01
+
0.05
0.01
C
R
+
ns
0.01
-
-
-
+
ns
0.05
average
ns
0.01
0.01
0.01
ns
0.01
* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle stimulation. All recordings were
(after a right DC lesion) on the control and deafferented sides.

Table 3-3. Results of statistical comparisons between pre-lesion and post-lesion frequency-response functions for the
p90-n50 complex. Significance level is given (ns = not significant).
monkey
foot
mech
stim
slope
y-int
elect
stim
slope
y-int
ankle
stim
slope
y-int
F
R
-
-
-
+
ns
ns
-
-
-
F
L
+
ns
0.05
+
ns
ns
-
-
-
S*
R
+
ns
0.01
+
ns
0.01
+
ns
0.05
C
R
+
ns
0.01
-
-
-
+
ns
0.05
average
ns
0.01
ns
ns
ns
0.01
* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle stimulation. All recordings were
(after a right DC lesion) on the control and deafferented sides.

Figure 3-3. Averaged pre-lesion evoked potential,
recorded over SI cortex in response to mechanical
stimulation of the foot (monkey S). Solid line
represents the average of responses to 210 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.

71
Mechanical stimulation

Figure 3-4. Pre-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 - 10 pps (right of trace). From
210 to 297 averages were accumulated from recordings on 5 days.

Amplitude
Mechanical stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
1 0 pps
1.5 pps
OJ

Figure 3-5. Post-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 to 10 pps (right of each trace).
From 1065 to 1183 averages were accumulated from recordings on 20 days.

Amplitude
I 10 uV
Mechanical stimulation
post—lesion
i 1 r
200 300
time (ms)
1.5 pps
2.5 pps
5.0 pps
7.5 pps
1 0 pps
1.5 pps
i 1 ' 1
400
«-4
0
100
500

Figure 3-6. Combined averages of 3 monkeys' evoked
potentials in response to mechanical stimulation,
before and after a DC lesion. Amplitudes are expressed
as percent of the pre-lesion response to 1.5 pps.
Error bars are + 1 SE. (TOP) The amplitude of the
p20-n50 complex. (BOTTOM) The amplitude of the p90-
n50 complex. Solid line along each x-axis represents
the mean amplitude of the noise, and the short dashes
represent the 95% confidence interval of that noise.

Amplitude (sg control: pre—lesion) Amplitude (% control: pre-lesion)
77
100-1
80-
60-
40-
20-
P20-N50
Ik
-- \
'll- ~ __
- -£]
-sr
i i r
2 4 6 8
Stimulus frequency (pps)
~i
10
P90-N50
100-1
80-
60-
40-
20-
" E3- —
n
i 1 1 r
2 4
1 1 1 1 1
6 8 10
Stimulus frequency (pps)
lesion
-lesion
lesion
-lesion
0

Figure 3-7. Combined averages of 3 monkeys' evoked
potentials in response to mechanical stimulation,
before and after a DC lesion. Amplitudes are expressed
as percent of either the pre-lesion or post-lesion
response to 1.5 pps. (TOP) The amplitude of the p20-
n50 complex. (BOTTOM) The amplitude of the p90-n50
complex. Error bars are + 1 SE.

Amplitude (s? control: 1.5 pps) Amplitude (% control: 1.5 pps)
79
100-,
80-
60-
40-
P20-N50
20-
0-4-
0
100-1
80-
60-
40-
—i 1 1 1 1 1 1 1 1
2 4 6 8 10
Stimulus frequency (pps)
P90-N50
20-
o-| 1 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
lesion
-lesion
lesion
-lesion

Figure 3-8. The averaged pre-lesion evoked potential
recorded over SI cortex in response to electrocutaneous
stimulation of the foot (monkey S). Solid line
represents average of responses to 303 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.

81
Electrocutaneous stimulation
n50
-40H—
-100
-50
~~50 ^00 1~50 200 250
time (ms)
o

Figure 3-9. Pre-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 - 10 pps (right of each trace).
From 303 to 320 averages were accumulated from recordings on 5 days.

Amplitude
electrocutaneous stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
1 0 pps
1.5 pps
00
OJ

Figure 3-10. Post-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 to 10 pps (right of each trace).
From 1160 to 1239 averages were accumulated from recordings on 20 days.

Amplitude
electrocutaneous stimulation
post—lesion
I 10 uV
1.5 pps
2.5 pps
5.0 pps
7.5 pps
t 1 1 1 1 r~
200 300 400
time (ms)
1 0 pps
1.5 pps
00
Ul
0
100
500

Figure 3-11. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
before and after a DC lesion (3 lesions). Amplitudes
are expressed as percent of the pre-lesion response to
1.5 pps. Error bars are + 1 SE. (TOP) The amplitude of
the p20-n50 complex. (BOTTOM) The amplitude of the
p90-n50 complex. Solid line along each x-axis
represents the mean amplitude of the noise, and the
short dashes represent the 95% confidence interval of
that noise.

Amplitude (sg control: pre—lesion) Amplitude (% control: pre —lesion)
87
100-1
80-
60-
40-
20-
EJ- —
cj-
0-| 1 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
100-1
60-
20-
0-| 1 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)

Figure 3-12. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
before and after a DC lesion (3 lesions). Amplitudes
are expressed as percent of either the pre-lesion or
post-lesion response to 1.5 pps. Error bars are + 1 SE.
(TOP) The amplitude of the p20-n50 complex. (BOTTOM)
The amplitude of the p90-n50 complex. Lines drawn
through data points are least-squares-fit.

Amplitude (% control; 1.5 pps) Amplitude (se control: 1.5 pps)
89
P20-N50
40-
20-
oH 1 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
100-)
80-
60-
40-
20-
Oi i i 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)

Figure 3-13. The averaged pre-lesion evoked potential
recorded over SI cortex in response to electrocutaneous
stimulation of the ankle (monkey C). Solid line
represents average of responses to 320 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.

91
Ankle stimulation
30 n
>
=3
“O
Z3
CL
£
<
-30
-100
50
100
150 200
250
time (ms)
o

Figure 3-14. Pre-lesion evoked potentials in response to different
stimulus frequencies (monkey C). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 - 10 pps (right of each trace).
From 319 to 320 averages were accumulated from recordings on 5 days.

Amplitude
Ankle stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
1 0 pps
1.5 pps
VO
OJ

Figure 3-15. Post-lesion evoked potentials in response to different
stimulus frequencies (monkey C). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 to 10 pps (right of each trace).
From 312 to 320 averages were accumulated from recordings on 20 days.

Amplitude
Ankle stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
1 0 pps
1.5 pps
VO
U1

Figure 3-16. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
of the ankle. Recordings were made from the normal and
DC-deafferented cortex. Amplitudes are expressed as
percent of the without-lesion response to 1.5 pps.
(TOP) The amplitude of the p20-n50 complex. (BOTTOM)
The amplitude of the p90-n50 complex. Solid line along
each x-axis represents the mean amplitude of the noise,
and the short dashes represent the 95% confidence
interval of that noise.

Amplitude (sg control: normal) Amplitude (% control: normal)
97
P20-N50
60-
40-
20-
0-| 1 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
P90-N50
normal
deafferented
normal
deafferented

Figure 3-17. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
of the ankle in the presence and absence of a DC
lesion. Amplitudes are expressed as percent of either
the deafferented or normal response to 1.5 pps. (TOP)
The amplitude of the p20-n50 complex. (BOTTOM) The
amplitude of the p90-n50 complex.

Amplitude (% control: 1.5 pps) Amplitude (% control: 1.5 pps)
99
100-,
80-
60-
P20-N50
TD
40-
20-
0H i i i | 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
P90-N50
normal
deafferented
normal
deafferented

100
Acute Recordings
Two stimulus configurations were used to record evoked
potentials from anesthetized animals; electrocutaneous
stimulation was delivered to the thenar eminence of the foot
and to the ankle. Electrode penetrations were made at about
1 mm increments, typically covering more than 1/2 square cm
of SI cortex.
Histology. Figure 3-18 shows a sagittal section taken
from a macaque cortex 7 mm from the midline (Winters et al.,
1969). The central sulcus (CS), post-central sulcus (PCS),
intra-parietal sulcus (IPS) and cingulate sulcus (CgS) can
be clearly seen in this figure. Two of these landmarks
(central sulcus and cingulate sulcus) are also on a
representative section (Figure 3-19), which was taken about
2 mm from the midline. Figure 3-19 shows the distribution
of electrode penetrations in the normal animals (top) and
the DC deafferented animals (bottom). It shows that ninety-
eight percent of the electrode penetrations were located in
the deep layers or underlying white matter of Brodmann's
areas 3,1 and 2. Two penetrations were localized to the
most caudal aspect of area 4, along the midline.
The histological reconstructions of the DC lesions for
the acute experiments is shown in Figure 3-2 for monkey F
and C and for monkey R6 in Figure 3-20. See the Histology
section under Chronic Recordings for discussion of the

101
lesions in monkeys F and C. Monkey R6 had a complete lesion
of the right DC between T4 and T5. There was a slight
involvement of the left DC and the right DL tracts, but
there was little involvement of the spinal grey matter.
Since this was a long term lesion (> 1 yr), there was
noticeable shrinkage of the right DC.
Recordings. The waveforms shown in Figure 3-21 were
recorded at two different locations in normal cortex
following foot stimulation and ankle stimulation. This
Figure shows that responses to the 10 pps stimulus was
suppressed relative to the 1.5 pps stimulus for both the
foot and ankle stimulation; this was typically the case.
The first negative peak was present most reliably across all
locations in cortex. The mean latency of the first
potential from the thenar in the no lesion condition was
22.0+0.79 ms (+SE), whereas the latency in the presence of a
lesion was 23.6+0.83 ms (not significant). The latency from
the ankle stimulus was 17.6+0.34 ms in the absence of a
lesion and 20.0+0.60 ms with the lesion (significant,
p<0.01). Although the ankle stimulation, with or
without a lesion, yielded a n20 latency that was about 4 ms
shorter than the thenar stimulus (significant, p<0.01), this
potential probably arose from the same generators under both
stimulus conditions. It is likely that the shorter latency
resulted from the larger stimulus to the ankle (typically 12
mA versus 5-6 mA).

Figure 3-18. Photograph of a sagittal section, taken 7 mm from the
midline of a Macaca nemestrina (Winters et al., 1969; page 13, panel
L7) . Reproduced with permission of publisher. (CS = central sulcus; pcs
= post-central sulcus; IPS = intra-parietal sulcus; CgS = cingulate
sulcus)

103

Figure 3-19. Approximate locations of all electrode
penetrations in the cortex. Penetrations are drawn on a
representative sagittal section of cortex taken about 2
mm from the midline. (TOP) Sixty-three penetrations
are shown in normal cortex. (BOTTOM) Fifty-four
penetrations are shown in DC-deafferented cortex. (A =
anterior; P = posterior; CS = central sulcus; 1,2 =
approximate location of border between Brodmann's areas
1 and 2.; 3,1 = approximate location of border between
Brodmann's areas 3 and 1)

105
Deafferented Cortex

Figure 3-20. DC lesion from one of the monkeys used in the acute
recordings. The drawing was made from a projection of the stained
spinal cord sections. The cross-hatched area represents the extent of
the lesion.


Figure 3-21. Evoked potentials recorded from normal
cortex during acute experiments in response to
electrocutaneous stimulation. Solid lines represent
the response to 1.5 pps, and the dashed lines represent
the response to 10 pps. (TOP) Responses recorded near
the CS in response to stimulation of the foot.
(BOTTOM) Response recorded near the 1,2 border in
response to ankle stimulation. (a and b represent the
time windows over which the peak-to-peak amplitude was
computed.

Amplitude (uV) Amplitude (uV)
109
ankle stimulation

Figure 3-22. Distribution of responses to 10 pps
relative to 1.5 pps in the normal and DC-deafferented
cortex. This histogram shows the number of
penetrations in which the response amplitude to 10 pps
fell within bins representing the percentage of the
response to 1.5 pps. The number on penetrations in
normal cortex was 63 and the number in deafferented
cortex was 54.

Number of Observations
111
no lesion
DC lesion
Response at 10pps relative to response at 1.5pps
(percent)

112
There was no systematic variation in frequency
suppression of the n20 response at different locations
within the SI cortex. The mean amplitude of the n20
potential at 10 pps relative to 1.5 pps (control frequency)
was not reliably different in the deafferented cortex (66.8%
± 30%; +SD) than in the normal cortex (63.2% + 14%). There
also was no difference between the recordings obtained in
response to foot or ankle stimulation (save for latency).
However, the amplitude at 10 pps (relative to 1.5 pps) in
the deafferented cortex was significantly more variable
(p<0.05) than in the normal cortex (Figure 3-22).
These results indicate that there was an increased
variability in the responsiveness of the cortex to
electrocutaneous stimulation of either the foot or the ankle
following a DC lesion. There did not appear to be any
difference between the normal and deafferented cortex in the
extent to which the n20 potential was suppressed at 10 pps.
However, the lesion did result in a significant increase in
the latency to the n20 peak following ankle stimulation.
DISCUSSION
The above results showed that interruption of the DCs
led to a decrease in amplitude of the epidural evoked
potential under all stimulus conditions and frequencies.
The early components of the post-lesion potentials showed a

113
change in the slope of the frequency-response function to
electrocutaneous stimulation of the foot. This increase in
frequency-dependent suppression was not observed for any
other stimulus condition. There also was an increased
variability in the amplitude of the n20 potential, in
anesthetized animals, following the DC lesion.
Chronic Recordings
The results from the awake recordings showed that there
was a large (40-80%) decrease in the amplitude of all
components of the evoked potential following a DC lesion.
This suggests that the DC in a normal animal contributes
significantly to the perception and detection of tactile
(non-noxious) stimuli. Indeed, the decrease in amplitude
following the lesion was most dramatic in the case of
mechanical stimulation; thus, the information about a
natural stimulus may be carried predominantly by the DCs.
It is likely that following such a lesion there would
be a shift in threshold for detection of a mechanical
stimulus. Although this was not found by Vierck (1977) with
von Frey stimulation, there is preliminary evidence from one
animal that a threshold shift of about 10-15 dB exists
following DC lesion for a mechanical stimulus that is in
constant contact with the skin (unpublished observations,
Friedman and Vierck). When a stimulus probe is in constant
contact with the skin, there is inevitably a form of

114
repetitive stimulation that results from small movements of
the foot relative to the probe. Because repetitive tactile
stimulation reduces the amplitude of SI cortical responses,
thresholds for detection should be elevated relative to
testing with infrequent stimulation by von Frey hairs. Such
an effect would be particularly pronounced for DC-
deafferented cortex, where responses to repetitive
stimulation are imbedded in background noise.
A change in the slope of the frequency-response
functions following a DC lesion was evident in the case of
the electrocutaneous stimulation of the foot. This is
physiological evidence that the DCs play a role in the
coding of stimulus frequencies between 1.5 and 10 pps. It
is possible that a slope change might have been detected in
the presence of the mechanical stimulus following the DC
lesion had the stimulus been large enough to drive the
response out of the noise.
There also was a slope change in the frequency-response
function to ankle stimulation in one of the two animals for
the p20-n50 complex on the DC deafferented side relative to
the control side. However, there were no pre-lesion data
from the ankle stimulation of this animal, and averaged
results from 2 animals showed no significant change in the
slope of the frequency-response function following the
lesion. This result suggests that frequency-dependent
suppression in exaggerated in animals with lesions for

115
stimulation of the distal extremity but not for more
proximal sites. The portions of SI representing the hand and
foot are much more dependent upon input from the DCs than
are other regions of SI (Dreyer et al., 1974).
These results on the whole shed some light on earlier
evoked potential studies following DC lesion. For example,
Gardner and Morin (1953; 1957) and Eidelberg and Woodbury
(1972) found no change in the evoked potential following
acute or chronic DC lesion (see Chapter 1 for details).
These studies were done under either pentobarbital or
chloralose anesthesia and used exclusively electrocutaneous
stimulation. In addition, it was not clear whether the
control records from before the lesion were taken from the
same population of neurons as the records after the lesion.
It is clear, however, that electrocutaneous stimulation is
not affected as much by the lesion as mechanical
stimulation. Thus, it is likely that their now dated
techniques were not sensitive enough to pick up a 60% change
in amplitude following a DC lesion.
The current findings are more consistent with the
findings of Andersson et al. (1972) and Cusick et al.
(1979), who found changes in the evoked potential following
DC lesions. Andersson et al. described a 4-5 ms increase in
latency and a 25% decrease in amplitude in response to
electrocutaneous stimulation of 1 pps. This is in contrast
to the current findings that showed a 60% decrease in

116
amplitude. It is possible that the effects of Nembutal
anesthesia attenuated the effects of the lesion. Cusick et
al. (1979) on the other hand, found about a 75% reduction in
amplitude of the evoked response to electrocutaneous
stimulation after a chronic DC lesion, while under ketamine
anesthesia. Once again, the anesthetic may have affected
the recordings, but given the difference between the
approaches, this is in reasonable agreement with the current
findings.
Acute Recordings
The recordings from the anesthetized cortex showed that
there was an increased variability in the n20 response to
electrocutaneous stimulation of the foot and ankle. It was
difficult to quantify later peaks of the evoked potentials,
because they varied with recording location in both relative
amplitude and latency. Thus, only the n20 potential was
examined.
The increased variability following a DC lesion could
suggest a variety of mechanisms. It is possible that the
increased variability was merely a reflection of the fact
that the potential is small and therefore closer to the
noise. It is also possible that the noise was greater in
the DC-deafferented cortex, although none of the awake
recordings showed this result. Perhaps the anesthesia has a
greater affect on the deafferented cortex than on the normal

117
cortex. Since the first peak was affected, it is likely
that the increased variability arose from subcortical
structures such as the thalamus.
In the awake recordings there was significantly greater
suppression at 10 pps, relative to 1.5 pps, in the DC-
deaf ferented cortex. It is not clear why the acute
recordings did not show a similar effect. It is possible
that the anesthetic raised the level of the noise during
these experiments, which in turn may have led to a floor
effect, similar to that seen in the awake recordings in
response to mechanical stimulation (see Figure 3-6).
Similarly, recordings from a restricted area of the cortex
in the acute experiments may have reduce the signal-to-noise
ratio. It is also possible that averaging across all the
locations of acute recordings masked an effect that was
present in only certain locations (e.g., at the center of
the representation of the distal extremity).
The increased variability in frequency-dependent
suppression at different recording locations in DC-
deafferented cortex is consistent with previous recordings
from units in SI cortex that responded to brush stimulation.
Vierck et al. (1990) found an increased variability in the
driving of DC-deafferented cortical units by each stimulus
in a repetitive train. Therefore, it is possible that the
focal evoked potentials were drawing from different groups

118
of neurons with different degrees of deafferentation by the
lesion.
Summary. These current findings are consistent with
the idea that a DC lesion produces a change in amplitude and
in the temporal processing of information arriving at the
cortex. This, in turn, can lead to a change in behavioral
thresholds and/or a change in relationships between
threshold and the frequency of stimulation. These changes
could arise either from limitations in the extent to which
the pathways spared by the lesion carry temporal information
or from an increased variability in responsiveness of the
cortex to each stimulus.

CHAPTER 4
PHYSIOLOGICAL CHANGES DURING RECOVERY FROM
A DORSAL COLUMN LESION
Following a DC lesion, a number of behavioral tasks
show significant improvement from an initial deficit that
eventually return to pre-lesion levels of performance. For
example, two-point discrimination (Levitt and Schwartzman,
1966), weight discrimination (DeVito et al., 1964), proximal
limb movements (Vierck, 1978a) and tactile size
discrimination (Vierck, 1973) recover from the lesion to
the DCs. This recovery can take anywhere from 1 to 6
months.
One problem with these findings is that it is not clear
whether the recovery resulted from neural plasticity or from
the animal learning to attend to different sensory cues.
For example, it is possible that the animals learned to
attend to the information normally carried in the pathways
spared by the lesion. On the other hand, it is also
possible that there is a change in the neural connectivity
of the spared pathways to compensate for the loss of the
DCs. These changes could take place in the dorsal horn
and/or dorsal column nuclei, where the primary afferents
synapse (Goldberger and Murray, 1982). Changes could also
119

120
occur in the thalamus (Garraghty and Kass, 1991; Rausell et
al., 1992) or cortex (Merzenich et al., 1984; Pons et al.,
1991) .
This line of reasoning was the impetus for the
experiments below. If the cortical evoked potential changed
over weeks after a DC lesion, this would provide evidence
for changes in connectivity of the spared pathways. An
alteration in the early peak would suggest a subcortical
change because that peak arises from input to layer IV and
its associated depolarization. If a change were restricted
to one of the later peaks, this would reflect a cortical
modification following the lesion, since those peaks arise
from a spread of intracortical activity. No change in the
response could result from the evoked potential measure
being insensitive to changes that occur, but it would also
indicate that there was not a substantial reorganization
taking place within the spared pathways.
METHODS
The methods for these experiments were similar to those
outlined in Chapter 3; therefore, they will only be briefly
outlined here. Any differences in methodology will be
noted.

121
Subjects and Training. The subjects were the three
female stumptailed macaques that were used in the awake
recordings (Chapter 3). Recordings were obtained five or
six days a week. The animals were led into the laboratory on
a leash and seated comfortably in a plexiglás primate chair.
They were gradually adapted to the primate chair and the
stimulation.
Two of the animals were also trained (once a week) on a
grasping task before the DC lesion was made. Grasping has
previously been shown (Vierck, 1978a) to be affected by such
a lesion and to reveal considerable recovery with time.
Therefore, this provided an assay for the integrity of the
lesion and for recovery of function following the lesion.
The animals were trained to pick up banana slices and small
marshmallows with each foot. The number of successful
attempts was noted, and, on successful attempts, the time it
took (latency) for the animal to place the food in its mouth
(latency) was measured with a stopwatch.
Surgery. Following chair training, epidural recording
electrodes were implanted over SI cortex. This was done
under sterile conditions at the University of Florida animal
surgery facility. After pre-lesion data were collected, a
unilateral interruption of the DC was made at a mid-thoracic
level (see Chapter 3 Methods for details).

122
Stimulation and Recording. On a daily basis,
recordings were made in response to electrocutaneous and
mechanical stimulation of the thenar eminence of the foot.
The signals were amplified and saved on magnetic tape for
off-line analysis. The amplifier was calibrated once a week
to ensure that there was no drift in the amplification over
time. The signal was also averaged on-line to monitor the
evoked potential during each recording session.
Data analysis. All data were analyzed off-line. The
"raw" evoked potential records were read off magnetic tape,
low-pass filtered (100 Hz), and digitized (1000 Hz, 1 ms bin
width) by commercially available software and an A-D board
(RC Electronics). The digitized records were converted into
ASCII files for further analysis by software written in 'C
(by the author).
The evoked potentials were first analyzed by discarding
any evoked potential traces that fell outside of a user
specified amplitude window (usually > + 300 uV). This was
intended to reject traces that contained movement artifact.
The remaining traces were then compressed and saved on disk.
Across days, these compressed files were then copied
together in series for analysis. The average amplitude of
the p20, n50 and p90 peaks from each recording session (day)
were plotted as a function of days post-lesion and were
tested to determine whether the slope was significantly

123
different than zero (p<0.05). An analysis of variance
(repeated measures) was also done in conditions that showed
no significant slope to determine if time (days post-lesion)
was a significant variable.
The statistical analyses were all done by programs
written in 'C by the author. A t-test was used to test for
significantly different slopes (Mendenhall et al., 1986; pg.
464). This was done first by fitting a linear (least-
squares-fit) function to the data. Then the mean and
variance of the estimates of the slope were used to compute
the test statistic 't.' This was a conservative test. The
responses from the individual animals were normalized before
they were averaged together. This was done first by
computing the root-mean-squared (rms) amplitude of each
animal's response across post-lesion days. Then the
responses from each of the animals was multiplied by a
constant so as to equate each of the individual animal's rms
values with each other. In this way, the rms amplitude
across days post-lesion were equal across animals before the
individual animals were averaged together.
RESULTS
Histology
The recording electrodes were the same in this
experiment as in the chronic recording experiments (Chapter

124
3, Figure 3-1). The DC lesions are shown in Figure 3-2 and
were all complete. See Chapter 3 (Histology) for further
details.
Grasping
Two animals learned to grasp food with each foot; a
third animal was unable to learn the task. The averaged
results from the two animals, tested once a week, are shown
in Figure 4-1. This Figure shows, on the top, the effect of
a DC lesion on the percent successful attempts at grasping
each food item (foot ipsilateral to lesion). On the bottom
the control (contralateral) foot is shown. Both animals
showed a significant (p<0.05) decrease in the percentage of
successful attempts following the DC lesion -- from 98%+2%
(monkey C) and 80%+12% (monkey S) on the 3 sessions (weeks)
before the lesion to 60%+10% (monkey C) and 40%+12% (monkey
S) on the 3 sessions immediately after the lesion.
The latency results showed that the animals' successful
grasps took slightly longer to make after the lesion.
Monkey S averaged 3.9+0.5 s in the three sessions before the
lesion, whereas she averaged 4.4+0.3 s in the three sessions
after the lesion. This was not a significant increase.
However, monkey C showed a significant (p<0.01) increase
following the lesion. She went from 3.1+0.3 s on the three
sessions before surgery to 5.6+0.7 s on the three sessions
after the lesion.

125
Recordings
All three animals showed a significant change in p90
amplitude over three months following a DC lesion under one
of the recording conditions. Two animals (monkey F and
monkey C) showed a significant (p<0.05) increase over time
in p90 amplitude following the lesion, whereas monkey S
showed that time was a significant (p<0.05) variable. On
the other hand, some stimulus and recording conditions did
not show significant increase or change over time. Monkey S
showed no significant effect of time in response to the
mechanical stimulus, and monkey F showed a significant
decrease in all potentials on both sides of the cortex after
the second lesion. Since there was such a diversity of
results, each condition will be discussed separately.
Monkey F showed the largest increase in p90 amplitude
following the first (right) DC lesion. Figure 4-2 shows the
response over time to electrocutaneous stimulation (1.5 pps)
of the right foot. This increase was significant for p90
(p<0.05) but not for either of the other two peaks on the
deafferented side or for any peak on the control side.
These recordings occurred over 90 days after implanting the
recording electrodes. However, following the second lesion,
which occurred at about 150 days after the implantation,
there was a continuous decrease in the amplitude of all
peaks recorded on both sides of the cortex (Figure 4-3 shows
the p90 response only). These recordings were collected

126
until about 220 days after the recording implant.
Monkey C also showed an significant (p<0.05) increase
in the p90 amplitude following a DC lesion, although this
was not as large an increase as for monkey F. Figure 4-4
shows this result in which p90 amplitude in response to a
1.5 pps mechanical stimulus to the right foot is plotted as
function of days following the right DC lesion. The left
foot was about 50% deafferented by the right DC lesion (see
Figure 3-2). This foot showed no significant increase in
amplitude after the lesion; however, time was a significant
variable (p<0.05).
Monkey S showed an insignificant increase in p90
amplitude after the lesion; however, there was a significant
change (p<0.05) in amplitude over time in response to
electrocutaneous stimulation following the lesion (Figure 4-
5). The p90 response to the mechanical stimulus, although
it was similar in shape to the electrocutaneous response,
did not vary significant over time (Figure 4-6).
Since there was a significant change or increase in the
p90 amplitude over time in each of the three animals under
some condition, these specific instances will be combined
below in an effort to describe the shape of this effect when
it occurs. Also, this procedure facilitated comparisons
ywith the effect of time on other peaks and on the potential
recorded from normal cortex. Before the results from each
animal were combined, the responses were normalized as
described in the Methods.

Figure 4-1. The effect of a unilateral DC lesion on
pedal grasping. Average performance of two monkeys (S
and C) on grasping food items with their feet is shown
before the lesion (weeks -8 to -1) and after the lesion
(weeks 1-7). (TOP) Performance with the DC-
deaf ferented foot. (Bottom) Performance with the foot
spared of the lesion.

Percent Successful Grasps Percent Successful Grasps
128
DC-deafferented foot
-8 -7
-6 -5 -4 -3 -2 -1 1 2 3 4 5
Weeks post DC-lesion
Control Foot
Weeks post DC-leslon

Figure 4-2. Time course (days) of changes in the
evoked potential amplitude following a DC lesion
(monkey F; electrocutaneous stimulus). Recordings over
SI cortex contralateral to a unilateral DC lesion are
shown. Solid line is a least-squares-fit to the data
points.

130

Figure 4-3. Time course (days) changes in of the
evoked potential amplitude following a the second DC
lesion after a long term (> 150 days) implant (monkey
F). Recordings made from both sides of the cortex are
shown. Solid lines are from a least-squares-fit to the
data points.

p90 Amplitude (uV)
132
left foot
right foot

Figure 4-4. Time course (days) of changes in the
evoked potential amplitude following a unilateral DC
lesion (monkey C; mechanical stimulus). Recordings
over SI cortex contralateral to the DC lesion are
shown. Solid line is a least-sguares-fit to the data
points.

134

Figure 4-5. Time course (days) of changes in the
evoked potential amplitude following a unilateral DC
lesion (monkey S; electrocutaneous stimulus).
Recordings over SI cortex contralateral to the DC
lesion are shown. Solid line is a least-squares-fit
the data points.

136

Figure 4-6. Time course (days) of changes in the
evoked potential amplitude following a unilateral DC
lesion (monkey S; mechanical stimulus). Recordings
over SI cortex contralateral to the DC lesion are
shown. Solid line is a least-squares-fit to the data
points.

138
40 -i
30-
>
zs
~o
=3
CL
O
CD
CL
10
o-
-10
A
Monkey S
mechanical stimulus
A
aa
days post—lesion
"^A
i i i i 1 1 1 1 1 1
0 10 20 30 40 50 60 70 80 90 100

Figure 4-7. Time course (days) of changes in the
evoked potential amplitude following a DC lesion for
three monkeys. The p90 response of the animals were
normalized (see Methods). Recordings over SI cortex
contralateral to the DC lesion are shown. Solid line
is a least-squares-fit to the data points.

p90 amplitude (uV)
140
monkey F
monkey S
monkey C

Figure 4-8. Time course (days) of changes in the
evoked potential amplitude following a DC lesion for
three monkeys. The p20 responses of the animals were
normalized (see Methods). Recordings over SI cortex
contralateral to the DC lesion are shown. Solid line
is a least-squares-fit to the data points.

p20 amplitude (uV)
142

Figure 4-9. Time course (days) of changes in the
evoked potential amplitude following a DC lesion for
two monkeys. The p90 responses of the animals were
normalized (see Methods). Recordings over normal SI
cortex ipsilateral to the DC lesion are shown. Solid
line is a least-squares-fit to the data points.

p90 amplitude (uV)
144
40-
30-
20-
0-
Combined response (normalized)
control side
w A
A
A X A
X X
AZ? a A
A x
A
A
X
X
A
A monkey F
x monkey S
! 1 1 1 1 1 1 1 1 1
0 10 20 30 40 50 60 70 80 90 100
days post—lesion
-10

Figure 4-10. Time course (days) of changes in the
evoked potential amplitude before a DC lesion in 3
monkeys. The p90 responses of the animals were
normalized (see Methods). Recordings over SI cortex on
both sides of the cortex are shown. Solid line is a
least-squares-fit to the data points.

p90 amplitude (uV)
146
days

Figure 4-11. Time course (days) of changes in the
evoked potential amplitude (p90) averaged across
animals. The data from three monkeys, shown in Figure
4-7, were averaged into 10 day blocks of time. Each
block contained anywhere from 2 to 14 values with a
median of 6. Error bars are + 1 SE.

148
40 n
Averaged Blocks
-10-
i i i i i i i i 1 1
0 10 20 30 40 50 60 70 80 90 100
days post—lesion

149
A scatter plot of the normalized responses after the DC
lesion is shown in Figure 4-7. The combination of data from
the three animals revealed a significant (p<0.05) increase
in p90 amplitude over time following the lesion. Figure 4-8
shows the p20 amplitude recorded on the same days. This
peak increased over time, but the effect was not
significant. In the two animals with a predominantly
unilateral DC lesion (S and F), the p90 amplitude from the
control side is shown in Figure 4-9. Figure 4-10 shows pre¬
lesion recordings over time from both sides of all three
animals. Thus, both the control side and the pre-lesion
responses were relatively stable over time in the absence of
a DC lesion.
The results shown in Figure 4-7 were averaged into
blocks of 10 days. The results of this computation are
shown in Figure 4-11, where each symbol represents the mean
(+SE). This function significantly increased across days
(p<0.05) and a post-hoc test (Tukey) showed that the 20 day
point was significantly greater (p<0.05) than the 10 day
point. Thus, there was a significant increase in the p90
amplitude from 10 to 20 days after the lesion under these
conditions.
In summary, the results suggest that there were
instances in which there was a significant increase in
amplitude of the p90 response following a DC lesion. This
result was not observed in the shorter latency peaks, nor

150
was it observed on the control side. The increase in p90
amplitude also coincided with behavioral recovery on a
grasping task, suggesting that the change has functional
significance.
DISCUSSION
There was a significant change in the p90 amplitude
following DC lesion in monkey S for electrocutaneous but not
mechanical stimulation. This difference may have resulted
from the poor signal-to-noise ratio for responses to
mechanical stimulation following DC lesion, whereas
responses to electrocutaneous stimulation were larger (see
Figures 4-5, 4-6 and 3-5). That is, the variability of
responses to the mechanical stimulus was considerable; this
may have masked what otherwise might have been significant
changes over time. On the other hand, monkey C showed a
significant increase in the p90 amplitude of responses to
mechanical stimulation following the lesion. This animal,
however, had a better signal to noise ratio (1.5 times
better) than monkey S. Therefore, it is likely that noise
contributed to the variability of the p90 amplitude for
monkey S to a greater extent during mechanical stimulation.
Monkey F had a different result after the first DC
lesion than was observed following the second. Following
the second lesion, this monkey showed a decrease in

151
amplitude over days in all the potentials measured. This
animal had received the recording implant more than 150 days
before the second lesion, and the recordings continued out
to nearly 220 days after the implant. Since there was a
decrease in all of the peaks on both sides following the
second lesion, it is likely that there was a degenerative
change in the recording properties of the implanted
electrodes over this time period.
These results provide evidence for functional recovery
from interruption of a major spinal pathway. This lesion
spared input from the periphery to alternative pathways with
central connections that run separately but have converging
inputs on to DC-lemniscal projection cells. Previous
investigators of functional recovery have generally used a
different model involving complete interruption of input
from a peripheral region. These peripheral lesions (e.g.,
Merzenich et al., 1984; Pons et al., 1991) produce both
short term (several days) and long term (months or years)
changes in the somatotopic map of the body after digit
amputation or dorsal rhizotomy (C2-T4). It was argued that
the short term changes (on the order of a few mm) could be
the result of alterations in synaptic efficacy at the
cortex; however, the long term changes ( > 1 cm) were
thought to arise from regions of the nervous system that
possess a smaller somatotopic map than the cortex.
For example, the thalamus (Rausell et at., 1992) showed

152
a decrease in calcium binding proteins specific for the
lemniscal afferent pathway, whereas there was an increase in
calcium binding proteins specific for spinal thalamic tract
neurons. There was also a down regulation of GABA (type A)
receptors (same monkeys as Pons et al., 1991). Indeed,
these changes were found in an area of high convergence: the
ventro-basal complex of the thalamus (Berkley, 1980; 1983).
Thus, these changes would affect responses at the cortical
level.
Garraghty and Kass (1991) also found changes in the
thalamus following median and ulnar nerve transection and
ligation, which completely deafferents a region of rostral
somatosensory pathways. Receptive fields on hairy skin were
observed in a region of the thalamus that normally has
receptive fields only on the glabrous skin of the hand.
Thus, there was a change, again in the ventro-basal complex
of the thalamus, in physiological response properties after
a 2-5 month recovery from nerve transection.
There also have been reports of sprouting in the dorsal
horn and dorsal column nuclei following dorsal rhizotomy in
cats (Goldberger and Murray, 1982). However, these changes
were limited to regions of the cord that normally receive
projections from a root spared of the rhizotomy and to
regions devoid of a detailed somatotopic map. Thus, it is
unlikely that sprouting at this level would lead to changes
in the somatotopic map in the cortex, though they might

153
contribute to changes in the amount or types of information
getting up the cord to the cortex. This is a situation
analogous to the present study, where a DC lesion partially
deafferents a portion of rostral somatotopic maps.
If the changes following DC-deafferentation were
derived from subcortical structures (i.e. the thalamus or
spinal cord), then it follows that a change in the evoked
potential should be evident in the first peak (i.e. the
input to and depolarization of layer IV). However, in the
present experiment, significant changes were observed in all
the animals in only the late (p90) peak. The early peak
showed an increasing trend, but it was not statistically
significant. Thus, it appears that the recovery was a
cortically mediated phenomenon. It is also possible that
there was a subcortical component that contributed to the
changes in cortical potential, but it was too small to be
detected with the evoked potential method.
Summary. There was a change in the amplitude of the
p90 component of the somatosensory evoked potential
following interruption of the DC pathway. This effect was
significant when the potential amplitude was large enough to
rise above the noise and when the recording electrodes had
not been implanted for more than 150 days. When the results
from the three animals were combined, the function showed a
precipitous increase in amplitude from 10 to 20 days post¬
lesion that corresponded with behavioral recovery on a

154
grasping task in two of the animals. The fact that the only
significant effect was in the p90 component of the evoked
potential suggests that the recovery was cortically
mediated.

CHAPTER 5
GENERAL DISCUSSION
The changes in the evoked potential following a DC
lesion, taken together with clinical findings in humans and
behavioral results in non-human primates suggest new
implications for the role of the DCs in conscious
perception. Not only are the DCs essential for normal
temporal processing of information, but they may also be
involved in the perception of static skin indentation. It
is possible that these deficits could arise at any one of a
number of locations along the neuraxis.
Neural Mechanisms
Nathan et al. (1986) described two cases where
interruption of the DCs affected the patient's ability to
feel the ongoing presence of a object placed in the hand.
These patients appeared to have difficulty perceiving
differences between graded pressure stimuli and feeling a
repeated tapping stimulus. Although these clinical findings
are difficult to interpret, owing to inadequate
psychophysical techniques and because of pathology involving
155

156
other pathways, these results are in accord with the current
findings.
Spinal cord
When the response properties of populations of cells in
the primate DC nuclei are compared to those in the DL and AL
tracts, there are striking differences. In the nucleus
gracilis, 84% of the cells respond to low threshold
mechanoreceptor activation (Ferrington et al., 1988),
whereas the lateral cervical nucleus contains 45% of cells
with low threshold mechanoreceptive responses (Downie et
al., 1988). Eight percent of the AL tract cells respond to
input from low threshold mechanoreceptors (Surmeier et al.,
1988). Of the low threshold mechanoreceptive cells in the
nucleus gracilis, 19% preferred static indentation over
brushing stimuli. The other two pathways contained too
small a number of such response types to be grouped
accordingly. Based on this population, it appears that
slowly adapting (SA) input may be routed predominantly
through the DC nuclei to the medial lemniscus. However,
investigations of afferent fiber sorting in fasciculus
gracilis have indicated that rapidly adapting (RA) primary
afferents project to nucleus gracilis in the DC, and SA
afferents project to the same target via the DL, after a
synapse in the dorsal horn (Whitsel et al., 1972; Brown,
1968) .

157
It is possible that interruption of the DCs produces a
substantial loss of RA input and also disrupts the coding of
static skin displacement resulting from a substantial
deafferentation of cells in the DC nuclei that receive input
from SA fiber types. That is, a combination of effects may
be required to account for the finding that patients with DC
lesions have difficulty perceiving static pressure (Nathan
et al., 1986). Similarly, one monkey, in preliminary
experiments, has shown a 10-15 dB threshold shift on a
detection task in which the stimulus probe was in contact
with the skin between the delivery of 10 ms indentations for
detection (Friedman and Vierck, unpublished observations).
If one assumes that the nervous system summates the
inputs from SA and RA fibers to detect each pulse, these
results indicate that input from both RA and SA afferents is
affected by a DC lesion. However, detection thresholds for
touch of the foot are not elevated by DC interruption when
the skin is not contacted between trials (Vierck, 1977).
This result indicates that elevation of touch threshold
depends upon testing situations such as constant contact,
which in generally associated with activation of SA
afferents. However, prolonged contact with an object
invariably is associated with small movements of the skin
relative to the object, providing a repetitive sequence of
phasic tactile stimuli. In the context of the demonstration
in the present study, in which frequency-dependent

158
suppression of evoked potential amplitudes was increased by
a DC lesion, it is understandable that detection thresholds
can be elevated when the testing conditions provide a source
of repetitive stimulation.
Interruption of afferents in the DC that terminate
peripherally in pacinian corpuscles (PC) could also have an
effect on the behavior and on the evoked potential
recordings in the present study. PC afferents are most
sensitive to high (ca. 200 Hz) frequencies of stimulation,
which provides a means for determining the contribution of
this fiber type to different ascending pathways. The DCs
carry a large number of PC type responses (Ferrington et
al., 1988), whereas the DL tract carries few or none (Downie
et al., 1988). Spino-thalamic tract neurons have not been
studied with vibrotactile stimuli in the monkey; however,
since fewer than 9% of the cells in this tract are low
threshold mechanoreceptors (a class that includes PC), PC
must constitute an even smaller percentage of AL fibers.
Thus, following a DC lesion, the reduction of PC input to
cortex should result in a lessened capability to follow high
frequencies of stimulation. This could in part be
responsible for the increase in frequency-dependent
suppression that was observed with electrocutaneous
stimulation.
Since electrocutaneous stimulation levels used in the
current study activated predominantly la, lb and some type

159
II fibers (A-alpha and A-beta; York, 1985), it follows that
this stimulus activated most of the non-nociceptive primary
afferent fiber types, including the PC. Electrocutaneous
stimulation by-passes the receptor end organ (York, 1985),
where the response characteristics of each fiber type are
determined (Vierck, 1978b). Therefore, an electrocutaneous
stimulus shows little or no frequency selectivity (Hahn,
1958) and probably stimulates a large number of PC fibers.
Also, when the mechanical stimulus at 10 pps was applied the
skin, in the present experiment, the onset velocity of the
pulses was sufficient to activate PCs. Alternatively, since
PCs respond to low frequencies of sufficient amplitude, it
is possible that the suprathreshold (0.4 mm) mechanical
stimulus at 10 pps was large enough to stimulate PC fibers.
The threshold for PCs at 10 Hz is about 30 urn (Bolanowski et
al., 1988). Therefore, it is possible that a reduction of
PC input following a DC lesion could contribute to the
decrease in evoked potential amplitude for both
electrocutaneous and mechanical stimulation, particularly
for high frequency stimulation.
Recordings from the post-synaptic pathways in the
spinal white matter suggest that the capacities of these
pathways to follow repetitive stimulation contributed to
poor temporal discrimination following the DC lesion. The
AL tract responses to 10 pps at pll and pl4 were suppressed
to about 70% and 90% of the DC response, respectively,

160
whereas responses from the DL column were about 80% of the
DC response. If the average suppression relative to the DC
response is computed, there was an overall 20% reduction in
the amplitude at 10 pps relative to the DC. If the simple
assumption is made that activity in the afferent pathways is
linearly summed at the cortex, then the result of this
computation is in agreement with the 20% increase in
frequency-dependent suppression that was observed in the
cortex following the DC lesion (see Figure 3-12).
Along a similar line of reasoning, if the amplitude of
the cortical evoked potential is proportional to the amount
of input to the cortex, then the cortical recordings from
animals with DC lesions are in accord with behavioral
deficits in frequency and duration discriminations. The
amplitude of the cortical response was reduced to 20-40% of
pre-lesion control responses to 1.5 pps, and the reduced
capacity to follow repetitive stimulation pushed the
response amplitude into the baseline noise at 10 pps. Since
the response to 10 pps was closest to the noise before the
lesion, it would follow that it would be most susceptible to
engulfment by the noise after the lesion.
Following a DC lesion, a substantial stimulus of 0.4 mm
was not sufficient to drive the cortical response above the
noise floor with stimulation at 10 pps. This suggests that
the DC is an important pathway for light mechanical
stimulation, which is supported by the unit findings

161
discussed above (Whitsel et al., 1972; Ferrington et
al.,1988; Downie et al.,1988; Surmeier et al.,1988).
However, the cortical response to electrocutaneous
stimulation at 10 pps was only suppressed by the lesion to
about 35% of the control amplitude (see Figure 3-11). This
finding, taken together with the fact that electrocutaneous
stimulation is less specific than a mechanical stimulus,
suggests that the electrocutaneous stimulus activates fibers
that do not carry purely tactile information. This line of
reasoning indicates that afferents supplying deep tissues
make a larger contribution to the DL and AL pathways than to
the DC pathway. Physiological recordings from the dorsal
columns have demonstrated this in both primates (Whitsel et
al., 1972) and cats (Dart and Gordon, 1973).
Thalamus
Another possible mechanism for the deficits in
processing of temporal information may result from changes
in the thalamus following a DC lesion. Ralston (1991) has
shown that medial lemniscal fibers arriving in the ventro-
basal complex of the thalamus have synapses on the proximal
dendrites of thalamic neurons that project to somatosensory
cortex. The same lemniscal cells also have synapses on
local GABA interneurons. These interneurons in turn have
synapses on the same cortical projection neurons as the
lemniscal fibers. Thus, a single thalamo-cortical cell

162
receives a synapse from a lemniscal fiber, and from that
same lemniscal fiber it receives input through an inhibitory
interneuron. These two synapse are immediately adjacent
along the dendrite, thereby providing a locus for
interactions between post-synaptic-potentials. This could
provide a mechanism for temporal filtering of input arriving
over the DC-medial-lemniscal pathway. The spino-thalamic
cells show inputs on to the same cortical projection cells
without any synapses on to the GABA interneurons. When the
DC input is lost (i.e. from a DC lesion), thalamic
inhibitory influences would be under less precise control
from afferent drive, and this could be manifest in terms of
a buildup or attenuation of inhibition during repetitive
stimulation.
Along a similar line of reasoning, a disruption of
inhibitory control could result in the increased variability
in frequency-dependent suppression that was observed in the
acute recordings from cortex deprived of input from the DC
(see Figure 3-22). For example, GABA neurons that project
from the reticular nucleus of the thalamus to the ventro-
basal complex of the thalamus have synapses on the thalamo¬
cortical cell dendrites as well as the local GABA
interneurons (Ralston, 1991). What is more, many reticular
nucleus cells have oscillatory firing patterns that are
regulated by the brainstem activating systems (Steriade et
al., 1990). Therefore, removal of the inhibitory control

163
that the DC-lemniscal system exerts over the projection
cells of the thalamus leaves these cells to the oscillatory
influences of the reticular nucleus. This could in turn
lead to variable responses to identical stimuli, depending
upon the excitation state of the thalamo-cortical cells.
Conclusions
It is possible that changes in behavioral and
physiological responses following a DC lesion have arisen
through a variety of mechanisms at a number of neural loci.
Reduction in the amplitude and enhancement of frequency-
dependent suppression of cortical evoked potentials could
have resulted from; 1) an overall decrease in total inputs
to the cortex and 2) a selective reduction in drive from RA
and PC afferents that are present in the DCs. It is also
possible that the extent to which the spared spinal pathways
followed high frequency stimulation contributed to the
deficits; however, it is unlikely that this was the sole
determining factor, given that the frequency suppression in
the spared pathways was small at 10 pps. Another likely
candidate for a locus of the deficit is the thalamus. There
are specialized excitatory and inhibitory influences in the
thalamus that are controlled by input from the dorsal column
nuclei and other brainstem centers that shape the output to
the cortex. To further elucidate these mechanisms
additional studies involving single unit analysis at
multiple sites within the nervous system is required.

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cortex. Brain 93:505-524.
Whitsel, B.L., Petrucelli, L.M., Ha, H., Dreyer, D.A. (1972)
The resorting of spinal afferents as antecedent to the
body representation in the postcentral gyrus. Brain
Behav. Evol. 5:303-341.
Willis, W.D., Trevino, D.L., Coulter, J.D., Maunz, R.A.
(1974) Responses of primate spinothalamic tract
neurons to natural stimulation of hindlimb. J.
Neurophysiol. 37:358-372.
Willis, W.D., Maunz, R.A., Foreman, R.D., Coulter, J.D.
(1975) Static and dynamic responses of spinothalamic
tract neurons to mechanical stimuli. J. Neurophysiol.
38:587-600.
Winters, W.D., Kado, R.T., Adey, W.R. (1969) A stereotaxic
atlas for Macaca nemestrina. University of California
Press. Berkeley and Los Angeles, California.

170
York, D.H. (1985) Somatosensory evoked potentials in man:
Differentiation of spinal pathways responsible for
conduction from the forelimb vs hindlimb. Progress in
Neurobiology 25:1-25.

BIOGRAPHICAL SKETCH
James Carl Makous was born to Marilyn and Walter on 9
August 1963, in Mt. Kisco, New York. After growing up in
Seattle and graduating from Ingraham High School in 1981, he
moved back east to New York to pursue his interest in
physics at the University of Rochester. After taking a few
courses in biopsychology he changed his major to
neuroscience. He then entered the laboratory of William E.
O'Neill and undertook experiments on the neurophysiology of
bat echolocation. After graduating in 1985 with a B.S. in
neuroscience, he worked in Robert Doty's laboratory under
the watchful eye of Sandy Bolanowski and participated in
experiments in visual psychophysics and physiology. He then
returned to his first love, the auditory system, when he was
accepted into the laboratory of John Middlebrooks at the
University of Florida. There he studied the neural basis of
sound localization. After 3 years, he transferred into the
laboratory of Charles Vierck where he began to study
temporal coding in the somatosensory system. While working
on his doctorate, he was happily married to Elizabeth Ann
Scott. He is now planning to return again to New York where
he will pursue his interests in somesthetic temporal coding
at Syracuse University.
171

I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
W, JÍjucs
David M. Green
Graduate Research Professor of
Psychology
I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
Associate Professor of Veterinary
Medicine

I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
Assistant Professor of Neuroscience
This dissertation was submitted to the Graduate Faculty
of the College of Medicine and to the Graduate School and
was accepted as partial fulfillment of the requirements for
the degree of Doctor of Philosophy.
May 1993
Dean, College of Medicine
Dean, Graduate School

UNIVERSITY OF FLORIDA
3 1262 08557 0371



46
Vierck, Jr. (sponsor) at a mid-thoracic level. A
laminectomy was performed on 2 mid-thoracic vertebrae; the
dura was pulled aside, and the dorsal cord was exposed. The
cord was visualized with a microscope, and the dorsal white
matter was interrupted with precision forceps between the
midline and the root entry zone on one side. The incision
was closed, and each animal was given antibiotics (Dualpen,
i.m.) for 1 week following the surgery.
Recording. The animals were seated in a primate chair
that provided loose restraint of the arms, legs and abdomen.
The male D-25 connector on the head was mated with a female
D-25. The female connector was connected, via individually
shielded cables, to a manual switch box located on the wall
adjacent to the animal. The switch box allowed a choice
between any reference electrode, located over frontal
cortex, and any "active" electrode over SI cortex. The two
outputs from the switch box were differentially amplified
(Bak; 10,000x), digitized (Vetter), and recorded on magnetic
tape (VCR) for off-line analysis. The signal was also
averaged on-line (286-computer; RC electronics software) to
monitor the evoked potential during each recording session.
Stimulation. While in the primate chair, the sole of
each foot was stimulated either electrocutaneously or
mechanically. An S88 stimulator (Grass) generated the
stimuli. The stimulus frequencies typically ranged from 1.5


Figure 3-2. DC lesions from the three monkeys used in the chronic
recordings. Each drawing was made from a projection of the stained
spinal cord sections. The cross-hatched areas represent the extent of
each lesion.


pathways in the lateral spinal columns were suppressed to
70-80% of their control values, whereas the DCs were not
suppressed at the same frequency.
In experiment 2, epidural evoked potentials were
recorded from implanted electrodes before and after a DC
lesion. In response to mechanical stimulation, the cortical
evoked potential at 10 pps could not be distinguished from
the background activity (noise) following the DC lesion.
The response to electrocutaneous stimulation showed a
frequency-dependent suppression at 10 pps, after the lesion,
that approximated a 20% reduction in amplitude.
In experiment 3, the cortical evoked potential was
monitored over weeks following the lesion. Under some
conditions, there was a significant increase in the
amplitude of a late (90 ms) peak following the DC lesion.
This increase was correlated with behavioral recovery on a
grasping task. There was no significant recovery for the
early peaks (20 and 50 ms).
In summary, a DC lesion caused an overall decrease in
amplitude of the cortical evoked potential. There was a
significantly greater frequency-dependent suppression of
responses to electrocutaneous stimulation at 10 pps
following the DC lesion. The reduction could be explained in
vi


165
Berkley, K.J., Budell, R.J., Blomqvist, A. Bull, M. (1986)
Output systems of the dorsal column nuclei in the cat.
Br. Res. Rev. 11:199-225.
Bolanowski, S.J.,Jr., Gescheider, G.A., Verrillo, R.T.,
Checkosky, C.M. (1988) Four channels mediate the
mechanical aspects of touch. J. Acoust. Soc. Am.
84(5):1680-1694.
Brown, A.G. (1968) Cutaneous afferent fiber collaterals in
the dorsal columns of the cat. Exp. Brain Res. 5:293-
305.
Cusick, J.F., Myklebust, J.B., Larson, S.J., Sanees, A.,Jr.
(1979) Spinal cord evaluation by cortical evoked
responses. Arch. Neurol 36:140-143.
Dart, A.M., and Gordon, G. (1973) Some properties of spinal
connections of the cat's dorsal column nuclei which do
not involve the dorsal columns. Brain. Res. 58:61-68.
DeVito, J.L., Ruch, T.C., Patton, H.D. (1964) Analysis of
residual weight discriminatory ability and evoked
cortical potentials following section of dorsal columns
in monkeys. Indian J. Physiol. Pharmacol. 8:117-126.
Downie, J.W., Ferrington, D.G., Sorkin, L.S., Willis,
W.D.,Jr. (1988) The primate spinocervicothalamic
pathway: Responses of cells of the lateral cervical
nucleus and spinocervical tract to innocuous and
noxious stimuli. J. Neurophysiol. 59:861-885.
Dreyer, D.A., Schneider, R.J., Metz, C.B., Whitsel, B.L.
(1974) Differential contributions of spinal pathways
to body representation in postcentral gyrus of Macaca
mulatta. J. Neurophysiol. 37:119-145.
Eidelberg, E., Woodbury, C.M. (1972) Apparent redundancy in
the somatosensory system in monkeys. Exper. Neurol.
37:573-581.
Emerson R.G., Pedley, T.A. (1990) Somatosensory evoked
potentials. In Current practice of clinical
electroencephalography. Second edition, Ed. D.D. Daly
and T.A. Pedley, Raven Press, Ltd., New York.
Ferrington, D.G., Downie, J.W., Willis, W.D., Jr. (1988)
Primate nucleus gracilis neurons: Responses to
innocuous and noxious stimuli. J. Neurophysiol.
59:886-907.


118
of neurons with different degrees of deafferentation by the
lesion.
Summary. These current findings are consistent with
the idea that a DC lesion produces a change in amplitude and
in the temporal processing of information arriving at the
cortex. This, in turn, can lead to a change in behavioral
thresholds and/or a change in relationships between
threshold and the frequency of stimulation. These changes
could arise either from limitations in the extent to which
the pathways spared by the lesion carry temporal information
or from an increased variability in responsiveness of the
cortex to each stimulus.


Table 3-3. Results of statistical comparisons between pre-lesion and post-lesion frequency-response functions for the
p90-n50 complex. Significance level is given (ns = not significant).
monkey
foot
mech
stim
slope
y-int
elect
stim
slope
y-int
ankle
stim
slope
y-int
F
R
-
-
-
+
ns
ns
-
-
-
F
L
+
ns
0.05
+
ns
ns
-
-
-
S*
R
+
ns
0.01
+
ns
0.01
+
ns
0.05
C
R
+
ns
0.01
-
-
-
+
ns
0.05
average
ns
0.01
ns
ns
ns
0.01
* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle stimulation. All recordings were
(after a right DC lesion) on the control and deafferented sides.


Amplitude (% control: 1.5 pps) Amplitude ( control: 1.5 pps)
79
100-,
80-
60-
40-
P20-N50
20-
o-\ 1 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
P90-N50
20-
"I 1 1 1 1 1 1 1 1 1
0 2 4 6 8 10
Stimulus frequency (pps)
lesion
-lesion
lesion
-lesion


Amplitude
Mechanical stimulation
1.5 pps
2.5 pps
5.0 pps
7.5 pps
10 pps
1.5 pps


38
tibial nerve, the DC pathway showed a significantly (p<0.05)
smaller suppression than any other subdivision of the spinal
cord, at stimulus frequencies of greater than 10 pps. At 10
pps or less, the three tracts were suppressed by nearly
comparable amounts. At 10 pps, suppression of the pl4
response from the AL tract was not significantly different
than the DC suppression. On the other hand, the DL and the
AL (pi1) responses were significantly (p<0.05) more
attenuated at 10 pps than the DC response.
Discussion
The principal result of this study was the observation
that ascending pathways in the lateral columns, which
emanated from the dorsal horn, are not profoundly suppressed
by repetition rates up to 10 pps. Therefore, behavioral
deficits in detection of 10 pps stimulation after
interruption of the dorsal columns are unlikely to be
attributed to a suppression of input to supraspinal targets
of pathways in the DL and AL tracts. At 10 pps, where the
tracts respond at 70% of the standard response or greater,
it is possible that any one of the pathways could contribute
significantly to the perception of a 10 pps stimulus.
Latency
The relative latencies of responses within the three


Figure 3-1. Locations of chronic recording electrodes in the three
monkeys used in the awake experiments. Arrows indicate 'active'
electrodes. The 'reference' electrode was always contralateral to and
frontal to the active one. (A = anterior; P = posterior; L = left; R =
right; CS = central sulcus; IPS = intra-parietal sulcus)


Figure 4-6. Time course (days) of changes in the
evoked potential amplitude following a unilateral DC
lesion (monkey S; mechanical stimulus). Recordings
over SI cortex contralateral to the DC lesion are
shown. Solid line is a least-squares-fit to the data
points.


27
T12


Figure 4-4. Time course (days) of changes in the
evoked potential amplitude following a unilateral DC
lesion (monkey C; mechanical stimulus). Recordings
over SI cortex contralateral to the DC lesion are
shown. Solid line is a least-squares-fit to the data
points.


158
suppression of evoked potential amplitudes was increased by
a DC lesion, it is understandable that detection thresholds
can be elevated when the testing conditions provide a source
of repetitive stimulation.
Interruption of afferents in the DC that terminate
peripherally in pacinian corpuscles (PC) could also have an
effect on the behavior and on the evoked potential
recordings in the present study. PC afferents are most
sensitive to high (ca. 200 Hz) frequencies of stimulation,
which provides a means for determining the contribution of
this fiber type to different ascending pathways. The DCs
carry a large number of PC type responses (Ferrington et
al., 1988), whereas the DL tract carries few or none (Downie
et al., 1988). Spino-thalamic tract neurons have not been
studied with vibrotactile stimuli in the monkey; however,
since fewer than 9% of the cells in this tract are low
threshold mechanoreceptors (a class that includes PC), PC
must constitute an even smaller percentage of AL fibers.
Thus, following a DC lesion, the reduction of PC input to
cortex should result in a lessened capability to follow high
frequencies of stimulation. This could in part be
responsible for the increase in frequency-dependent
suppression that was observed with electrocutaneous
stimulation.
Since electrocutaneous stimulation levels used in the
current study activated predominantly la, lb and some type


154
grasping task in two of the animals. The fact that the only
significant effect was in the p90 component of the evoked
potential suggests that the recovery was cortically
mediated.


81
Electrocutaneous stimulation
n50
40| r-
-100 -50
_50 1~00 150 200 250
time (ms)
o


Figure 3-17. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
of the ankle in the presence and absence of a DC
lesion. Amplitudes are expressed as percent of either
the deafferented or normal response to 1.5 pps. (TOP)
The amplitude of the p20-n50 complex. (BOTTOM) The
amplitude of the p90-n50 complex.


105
Deafferented Cortex


43
stimulation (e.g., von Frey hairs or brush stimuli) gains
access to the cortex more effectively than input which has
been preceded by recent stimulation (e.g., train of pulses).
2) It is possible that, following a DC lesion, there
is a change in the extent to which the entire cortical
evoked potential is suppressed by increasing frequency.
This result would suggest that information transmitted to
the cortex over the spared pathways is compromised by the
capacity for these alternate pathways (or partially
deafferented relays) to follow a 10 pps stimulus. Such a
frequency-dependent suppression of early and late peaks
would suggest that the locus of the effect is sub-cortical:
either at the dorsal horn or thalamus.
3) It is possible that, following the lesion,
different peaks in the cortical evoked potential would be
suppressed by different amounts, either in absolute
amplitude or in frequency-dependent suppression. For
example, it is possible that the first peak of the evoked
potential, which is associated with the depolarization of
layer four, would show no change in amplitude or frequency-
dependent suppression. If only the later peaks, associated
with the spread of information that arose from layer four,
showed an effect of the lesion, this would suggest that the
pathways spared by the lesion adequately carry the
information to the cortex, but that there are changes at the
cortical level following deafferentation that affect the


Figure 3-14. Pre-lesion evoked potentials in response to different
stimulus frequencies (monkey C). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 10 pps (right of each trace).
From 319 to 320 averages were accumulated from recordings on 5 days.


150
was it observed on the control side. The increase in p90
amplitude also coincided with behavioral recovery on a
grasping task, suggesting that the change has functional
significance.
DISCUSSION
There was a significant change in the p90 amplitude
following DC lesion in monkey S for electrocutaneous but not
mechanical stimulation. This difference may have resulted
from the poor signal-to-noise ratio for responses to
mechanical stimulation following DC lesion, whereas
responses to electrocutaneous stimulation were larger (see
Figures 4-5, 4-6 and 3-5). That is, the variability of
responses to the mechanical stimulus was considerable; this
may have masked what otherwise might have been significant
changes over time. On the other hand, monkey C showed a
significant increase in the p90 amplitude of responses to
mechanical stimulation following the lesion. This animal,
however, had a better signal to noise ratio (1.5 times
better) than monkey S. Therefore, it is likely that noise
contributed to the variability of the p90 amplitude for
monkey S to a greater extent during mechanical stimulation.
Monkey F had a different result after the first DC
lesion than was observed following the second. Following
the second lesion, this monkey showed a decrease in


Figure 4-5. Time course (days) of changes in the
evoked potential amplitude following a unilateral DC
lesion (monkey S; electrocutaneous stimulus).
Recordings over SI cortex contralateral to the DC
lesion are shown. Solid line is a least-squares-fit
the data points.


Figure 3-16. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
of the ankle. Recordings were made from the normal and
DC-deafferented cortex. Amplitudes are expressed as
percent of the without-lesion response to 1.5 pps.
(TOP) The amplitude of the p20-n50 complex. (BOTTOM)
The amplitude of the p90-n50 complex. Solid line along
each x-axis represents the mean amplitude of the noise,
and the short dashes represent the 95% confidence
interval of that noise.


159
II fibers (A-alpha and A-beta; York, 1985), it follows that
this stimulus activated most of the non-nociceptive primary
afferent fiber types, including the PC. Electrocutaneous
stimulation by-passes the receptor end organ (York, 1985),
where the response characteristics of each fiber type are
determined (Vierck, 1978b). Therefore, an electrocutaneous
stimulus shows little or no frequency selectivity (Hahn,
1958) and probably stimulates a large number of PC fibers.
Also, when the mechanical stimulus at 10 pps was applied the
skin, in the present experiment, the onset velocity of the
pulses was sufficient to activate PCs. Alternatively, since
PCs respond to low frequencies of sufficient amplitude, it
is possible that the suprathreshold (0.4 mm) mechanical
stimulus at 10 pps was large enough to stimulate PC fibers.
The threshold for PCs at 10 Hz is about 30 um (Bolanowski et
al., 1988). Therefore, it is possible that a reduction of
PC input following a DC lesion could contribute to the
decrease in evoked potential amplitude for both
electrocutaneous and mechanical stimulation, particularly
for high frequency stimulation.
Recordings from the post-synaptic pathways in the
spinal white matter suggest that the capacities of these
pathways to follow repetitive stimulation contributed to
poor temporal discrimination following the DC lesion. The
AL tract responses to 10 pps at pll and pl4 were suppressed
to about 70% and 90% of the DC response, respectively,


I certify that I have read this study and that in my
opinion it conforms to acceptable standards of scholarly
presentation and is fully adequate, in scope and quality,
as a dissertation for the degree of Doctor of Philosophy.
Assistant Professor of Neuroscience
This dissertation was submitted to the Graduate Faculty
of the College of Medicine and to the Graduate School and
was accepted as partial fulfillment of the requirements for
the degree of Doctor of Philosophy.
May 1993
Dean, Graduate School


Figure 3-11. Combined averages of 2 monkeys' evoked
potentials in response to electrocutaneous stimulation
before and after a DC lesion (3 lesions). Amplitudes
are expressed as percent of the pre-lesion response to
1.5 pps. Error bars are + 1 SE. (TOP) The amplitude of
the p20-n50 complex. (BOTTOM) The amplitude of the
p90-n50 complex. Solid line along each x-axis
represents the mean amplitude of the noise, and the
short dashes represent the 95% confidence interval of
that noise.


14
in the cortical evoked potential with behavioral changes
observed in animals recovering from DC lesions. The last
chapter discusses some possible mechanisms for the changes
in the cortical evoked potential that accompany DC
interruption.


Figure 4-2. Time course (days) of changes in the
evoked potential amplitude following a DC lesion
(monkey F; electrocutaneous stimulus). Recordings over
SI cortex contralateral to a unilateral DC lesion are
shown. Solid line is a least-squares-fit to the data
points.


Figure 3-7. Combined averages of 3 monkeys' evoked
potentials in response to mechanical stimulation,
before and after a DC lesion. Amplitudes are expressed
as percent of either the pre-lesion or post-lesion
response to 1.5 pps. (TOP) The amplitude of the p20-
n50 complex. (BOTTOM) The amplitude of the p90-n50
complex. Error bars are + 1 SE.


Amplitude
Ankle stimulation
pre lesion
1.5 pps
2.5 pps
5.0 pps
7.5 pps
10 pps
1.5 pps
VO
u>
T
100
200 300
time (ms)
400
o
500


REFERENCES
Allison, T., McCarthy, G., Wood, C.C., Stephen, J.J (1991)
Potentials evoked in human and monkey cerebral cortex
by stimulation of the median nerve: A review of scalp
and intracranial recordings. Brain 114:2465-2503.
Anderson, P., McC.Brooks, C., Eccles, J.C, Sears, T.A.
(1964) The ventro-basal nucleus of the thalamus:
Potential fields, synaptic transmission and
excitability of both presynaptic and post-synaptic
components. J. Physiol. (London) 174:348-369.
Andersson, S.A., Norrsell, K., Norrsell, U. (1972) Spinal
pathways projecting to the cerebral first somatosensory
area in the monkey. J. Physiol. 225: 589-597.
Andersson, S.A., Finger, S., Norrsell, U. (1975) Cerebral
units activated by tactile stimuli via a ventral spinal
pathway in monkeys. Acta Physiol. Scand. 93:119-128.
Arezzo, J.C., Vaughan, H.G.,Jr., Legatt, A.D. (1981)
Topography and intracranial sources of somatosensory
evoked potentials in the monkey. II. Cortical
components. Electroencephalogr. Clin. Neurophysiol.
51:1-18.
Beck, C., Rosner, B.S. (1968) Magnitude scales and somatic
evoked potentials to percutaneous electrical
stimulation. Physiol, and Behavior 3:947-953.
Berkley, K.J. (1980) Spatial relationships between the
terminations of somatic sensory and motor pathways in
the rostral brainstem of cats and monkeys. I. Ascending
somatic sensory inputs to lateral diencephalon. J.
Comp. Neurol. 193:283-317.
Berkley, K.J. (1983) Spatial relationships between the
terminations of somatic sensory and motor pathways in
the rostral brainstem of cats and monkeys. II.
Cerebellar projections compared with those of the
ascending somatic sensory pathways in lateral
diencephalon. J. Comp. Neurol. 220:229-251.
164


71
Mechanical stimulation


Figure 3-15. Post-lesion evoked potentials in response to different
stimulus frequencies (monkey C). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 to 10 pps (right of each trace).
From 312 to 320 averages were accumulated from recordings on 20 days.


54
were expressed as percent of the response to 1.5 pps.
Results
Chronic Recordings
Histology. The locations of the recording electrodes
for the three animals are shown in Figure 3-1 (arrows). The
active electrodes were either directly over or bordered the
SI cortex in all three animals. In monkey C, the active
electrodes (indicated by arrows) were located over the
posterior half of the precentral gyrus (in the motor strip).
The electrode used to record from the DC deafferented cortex
(on the left) was actually over the midline in monkey C.
However, the potentials from the two sides of the animal
were similar in shape and latency, and these potentials were
similar to those obtained in the other animals. Therefore,
it is likely that recordings from all three animals arose
from similar sources in the cortex.
The dorsal column lesions in all three animals were
complete and are shown in Figure 3-2. Monkey F received two
consecutive lesions separated by four months. The first DC
lesion (right side) was at spinal cord level T7, included
some of the grey matter in the dorsal horn and crossed the
midline in the most dorsal part of the left DC. The second
DC lesion in monkey F was between level T3 and T4 on the
left, and it included gray matter in the dorsal horn at the


9
hemisection of the cord decreased the number of units per
cortical penetration that could be driven by peripheral
stimulation. There was also a high number of units that
were spontaneously active and were driven unreliably. The
latencies of units did not appear to be longer than control
animals, but units were more often found on the hairy than
on the glabrous skin. Although most of the units tended to
be rapidly adapting, they typically could not follow
repetitive stimulation beyond 4 Hz.
These results are in general agreement with the results
of Dreyer et al. (1974), though they differ in the details.
Dreyer et al. found, in awake monkeys with chronic (21-72
days) DC lesions, that fewer numbers of units were driven by
peripheral stimulation, and the responses were less
reliable. In contrast to Andersson et al. (1975), they
found a high proportion of neurons that responded to deep
stimulation rather than light stimulation. There was a
cortical region, corresponding primarily to the center of
the hand and foot representations in areas 3b and 1, that
was nearly devoid of responses following DC lesion, whereas
the surrounding cortical areas (3a and 2) appeared more
normal in the nature and proportion of responses.
Until now the afferents in the fasciculus gracilis (FG)
from the foot have been presented as if they were
distributed in a pattern similar to that of the fasciculus
cuneatus (FC) from the hand. However, Whitsel et al. (1972)


16
mechanisms could regulate the extent to which spared
pathways contribute to perception.
It was this line of reasoning that led to the first set
of experiments. If the pathways emanating from the dorsal
horn were dramatically suppressed at 10 pps, then the dorsal
horn could be a neural locus of the behavioral deficit
observed following DC interruption. Therefore, experiments
were undertaken to record from the white matter tracts of
the cord in response to different stimulus frequencies, and
the extent to which each pathway was suppressed by
increasing frequencies was determined.
Methods
Animals
The subjects were three female macaques (1 Macaca
arctoides and 2 Macaca nemestrina) that weighed between 4.8
and 11.4 kg. They were housed in an outdoor communal
enclosure to maximize the animals' health and psychological
well being. The animals were maintained on a diet of Purina
monkey chow, fruit and water. Prior to the acute
experiments, these animals were used in two procedures: a
behavioral study in which they received a cortical lesion of
the arcuate gyrus, and an anatomical study in which they
received an injection of HPR into the lumbrical muscles of
each hand, one week prior to the acute experiment. Two


149
A scatter plot of the normalized responses after the DC
lesion is shown in Figure 4-7. The combination of data from
the three animals revealed a significant (p<0.05) increase
in p90 amplitude over time following the lesion. Figure 4-8
shows the p20 amplitude recorded on the same days. This
peak increased over time, but the effect was not
significant. In the two animals with a predominantly
unilateral DC lesion (S and F), the p90 amplitude from the
control side is shown in Figure 4-9. Figure 4-10 shows pre
lesion recordings over time from both sides of all three
animals. Thus, both the control side and the pre-lesion
responses were relatively stable over time in the absence of
a DC lesion.
The results shown in Figure 4-7 were averaged into
blocks of 10 days. The results of this computation are
shown in Figure 4-11, where each symbol represents the mean
(+SE). This function significantly increased across days
(p<0.05) and a post-hoc test (Tukey) showed that the 20 day
point was significantly greater (p<0.05) than the 10 day
point. Thus, there was a significant increase in the p90
amplitude from 10 to 20 days after the lesion under these
conditions.
In summary, the results suggest that there were
instances in which there was a significant increase in
amplitude of the p90 response following a DC lesion. This
result was not observed in the shorter latency peaks, nor


Figure 3-22. Distribution of responses to 10 pps
relative to 1.5 pps in the normal and DC-deafferented
cortex. This histogram shows the number of
penetrations in which the response amplitude to 10 pps
fell within bins representing the percentage of the
response to 1.5 pps. The number on penetrations in
normal cortex was 63 and the number in deafferented
cortex was 54.


123
different than zero (p<0.05). An analysis of variance
(repeated measures) was also done in conditions that showed
no significant slope to determine if time (days post-lesion)
was a significant variable.
The statistical analyses were all done by programs
written in 'C by the author. A t-test was used to test for
significantly different slopes (Mendenhall et al., 1986; pg.
464). This was done first by fitting a linear (least-
squares-fit) function to the data. Then the mean and
variance of the estimates of the slope were used to compute
the test statistic 't.' This was a conservative test. The
responses from the individual animals were normalized before
they were averaged together. This was done first by
computing the root-mean-squared (rms) amplitude of each
animal's response across post-lesion days. Then the
responses from each of the animals was multiplied by a
constant so as to equate each of the individual animals rms
values with each other. In this way, the rms amplitude
across days post-lesion were equal across animals before the
individual animals were averaged together.
RESULTS
Histology
The recording electrodes were the same in this
experiment as in the chronic recording experiments (Chapter


115
stimulation of the distal extremity but not for more
proximal sites. The portions of SI representing the hand and
foot are much more dependent upon input from the DCs than
are other regions of SI (Dreyer et al.f 1974).
These results on the whole shed some light on earlier
evoked potential studies following DC lesion. For example,
Gardner and Morin (1953; 1957) and Eidelberg and Woodbury
(1972) found no change in the evoked potential following
acute or chronic DC lesion (see Chapter 1 for details).
These studies were done under either pentobarbital or
chloralose anesthesia and used exclusively electrocutaneous
stimulation. In addition, it was not clear whether the
control records from before the lesion were taken from the
same population of neurons as the records after the lesion.
It is clear, however, that electrocutaneous stimulation is
not affected as much by the lesion as mechanical
stimulation. Thus, it is likely that their now dated
techniques were not sensitive enough to pick up a 60% change
in amplitude following a DC lesion.
The current findings are more consistent with the
findings of Andersson et al. (1972) and Cusick et al.
(1979), who found changes in the evoked potential following
DC lesions. Andersson et al. described a 4-5 ms increase in
latency and a 25% decrease in amplitude in response to
electrocutaneous stimulation of 1 pps. This is in contrast
to the current findings that showed a 60% decrease in


OI


Table 3-2. Results of statistical comparisons between pre-lesion and post-lesion frequency-response functions for the
p20-n50 complex. Significance level is given (ns = not significant).
monkey
foot
mech
stim
slope
y-int
elect
stim
slope
y-int
ankle
stim
slope
y-int
F
R
-
-
-
+
0.05
0.01
-
-
-
F
L
+
ns
0.01
+
ns
0.01
-
-
-
S*
R
+
ns
0.01
+
0.05
0.01
+
0.05
0.01
C
R
+
ns
0.01
-
-
-
+
ns
0.05
average
ns
0.01
0.01
0.01
ns
0.01
* Note: No pre-lesion evoked potentials were recorded from monkey S in response to ankle stimulation. All recordings were
(after a right DC lesion) on the control and deafferented sides.


5
primary afferents in the dorsal horn lasting greater that
100 ms; however, primary afferents in the DCs show an
inhibition lasting only 25-35 ms (Wall, 1958). Therefore,
since normal neuronal excitability in the dorsal horn can
have a refractory period of more than 100 ms, it is possible
that changes in perception following interruption of the DC
results from a restriction of temporal processing of
cutaneous information in pathways emanating from the spinal
grey matter.
If pathways other than the DCs are to code for touch,
it is important that the pathways arising from the dorsal
horn carry information about non-noxious, natural cutaneous
stimuli as opposed to information strictly from muscle
afferents. Indeed, a number of studies have shown that the
AL and DL tract fibers respond to natural stimulation of the
skin (Willis et al.,1974; 1975; Surmeier et al., 1988;
Downie et al., 1988) and that they contribute to cortical
responses (Andersson et al., 1975). However, few studies
have looked at frequency coding in the AL tract; the stimuli
used in these studies usually involved a static displacement
of the skin or hair.
The DL tract has been studied much less extensively in
the primate than in the cat, and the two species appear to
differ substantially in the size of the DL pathway
(Nijensohn and Kerr, 1975). Thus, the information carried
in this pathway in primates is not well characterized.


Figure 3-8. The averaged pre-lesion evoked potential
recorded over SI cortex in response to electrocutaneous
stimulation of the foot (monkey S). Solid line
represents average of responses to 303 stimulus
presentations, accumulated over 5 days. Dashed lines
are + 1 SE.


23
Spinal Recordings
Table 2-1 shows the peak latencies obtained for each
animal in each tract, averaged across all frequencies. The
'n' column corresponds to the number of frequency series
that were conducted in that tract for that animal. Monkey E
received a right DC lesion more than 2 months prior to the
recordings. Note that the AL response had two peaks that
differed in latency by 3 ms in two of the three animals.
There was a tendency for potentials evoked in the post-
synaptic pathways to have a slightly longer latency (0.3 4
ms) than the DC pathway.
Representative averaged responses from each tract are
shown in Figures 2-3, 2-4 and 2-5. These were derived from
one animal (Monkey D) on three separate penetrations. The
response from the DC (Figure 2-3) had a latency of 9.6 ms
and showed little suppression with high frequency
stimulation. There was almost no DC response from the
control foot. The response from the DL tract (Figure 2-4)
had a latency around 10.1 ms, but showed a more pronounced
suppression with increasing frequencies. At 50 pps the
potential was little more than 50% of the standard response
to 1.5 pps. The response from the control foot was small.
The AL tract had the most complex response (Figure 2-5).
The pll response was suppressed to nearly 50% at 10 pps,
whereas the pl4 response was not substantially suppressed
until 25 pps. However, the pl4 was completely abolished at


52
surgery was complete, and the animal's head was suspended by
the screw in the acrylic cap, the anesthetic was changed to
nitrous oxide (66%) and isoflurane 0.5-1.0% (Tigwell and
Sauter, 1992). The animal was then given a dose of
Pancuronium (0.03 mg/kg/3hrs i.v.) and put on an artificial
respirator (Harvard; 20 breaths/min; 10 ml/kg body mass).
The plane of anesthesia was monitored by the EEG, and the
expired C02 was maintained between 35 and 40 mm Hg.
Glass and Insl-x coated tungsten electrodes (impedance
= 50-200 kohms at 1000 Hz; see chapter 2 for electrode
construction) were lowered into the cortex with the
microdrive (Narishige). The electrode depth was chosen to
maximize the early negative potential (ca. 20 ms). In this
way, the recordings were always near to, but deeper than,
layer IV. Evoked potentials were differentially amplified
(10,000x), digitized (Vetter) and saved on magnetic tape
(VCR). The potentials were also filtered (3-300 Hz) and
averaged on-line (1 ms bin width; RC Electronics A-D board
and software). The averages were saved on disk in ASCII
format.
Stimulation. Electrocutaneous stimuli were delivered
to the thenar eminence and ankle of each foot. These
stimuli were similar to those described above in the Chronic
Recordings. The amplitude of the thenar stimulus was
typically 5-6 mA, whereas the ankle stimulus was 12 mA.


p90 Amplitude (uV)
132
o.
ID
A
Monkey F
electrocutaneous stimulus
(post left DC lesion)
o
o
r-O
A
A
* left foot
right foot
1 0 10 20 30 40 50 60 70 80 90 100
days post-lesion


Table 2-1. Latencies of evoked potentials and number of recordings from each subdivision of the
spinal cord. The latencies are listed for each animal in ms (re: stimulus artifact), and n corresponds
to the number of frequency series that were obtained at each site for each animal. Monkey E had a
left DC lesion 2 months prior to the recordings (see Figure 2-2), and therefore no recordings were
made from this DC tract in this animal.
monkey
DC
(ms)
n
DL
(ms)
n
AL p11
(ms)
n
AL p14
(ms)
n
E
11.4
3.0
10.8
4.0
10.9
3.0
13.1
3.0
D
9.6
2.0
10.1
5.0
10.6
5.0
13.9
5.0
K
9.9
3.0
11.0
4.0
-
-
15.3
1.0
ave
10.3
10.7
10.8
14.1
std
1.0
0.5
0.2
1.1
to
00


162
receives a synapse from a lemniscal fiber, and from that
same lemniscal fiber it receives input through an inhibitory
interneuron. These two synapse are immediately adjacent
along the dendrite, thereby providing a locus for
interactions between post-synaptic-potentials. This could
provide a mechanism for temporal filtering of input arriving
over the DC-medial-lemniscal pathway. The spino-thalamic
cells show inputs on to the same cortical projection cells
without any synapses on to the GABA interneurons. When the
DC input is lost (i.e. from a DC lesion), thalamic
inhibitory influences would be under less precise control
from afferent drive, and this could be manifest in terms of
a buildup or attenuation of inhibition during repetitive
stimulation.
Along a similar line of reasoning, a disruption of
inhibitory control could result in the increased variability
in frequency-dependent suppression that was observed in the
acute recordings from cortex deprived of input from the DC
(see Figure 3-22). For example, GABA neurons that project
from the reticular nucleus of the thalamus to the ventro-
basal complex of the thalamus have synapses on the thalamo
cortical cell dendrites as well as the local GABA
interneurons (Ralston, 1991). What is more, many reticular
nucleus cells have oscillatory firing patterns that are
regulated by the brainstem activating systems (Steriade et
al., 1990). Therefore, removal of the inhibitory control


49
blocks of days with similar stimulus conditions, and
comparisons between pre-lesion and post-lesion data were
based upon these blocked averages. To compare the evoked
potentials recorded under different conditions, the peak-to-
peak amplitudes of p20-to-n50 and n50-to-p90 were computed
(see Figure 3-3). This was done to avoid problems presented
by a fluctuating baseline, especially at different stimulus
frequencies and after the DC lesion, when baseline
fluctuations approached the amplitude of the evoked
potential.
Estimates of baseline levels of noise were made by
calculating the mean amplitude and variance of the
recordings obtained during the 250 ms before each stimulus
onset at 1.5 pps. This was done by taking a random sample
of 1 ms bins. Each sample was taken from a 10 ms window,
once every 20 ms. This procedure yielded results that did
not differ significantly (p<0.05) from sampling once every
50 ms (at 50 ms the autocorrelation function was zero).
However, this technique provided a better estimate of the
noise by increasing the number of samples.
The statistical analyses were all done by programs
written in C by the author. A t-test was used to identify
significantly different slopes and y-intercepts (Mendenhall
et al., 1986; pg. 464) for functions relating response
amplitude to stimulus frequency. This was done first by
fitting a linear (least-squares-fit) function to the data.


156
other pathways, these results are in accord with the current
findings.
Spinal cord
When the response properties of populations of cells in
the primate DC nuclei are compared to those in the DL and AL
tracts, there are striking differences. In the nucleus
gracilis, 84% of the cells respond to low threshold
mechanoreceptor activation (Ferrington et al., 1988),
whereas the lateral cervical nucleus contains 45% of cells
with low threshold mechanoreceptive responses (Downie et
al., 1988). Eight percent of the AL tract cells respond to
input from low threshold mechanoreceptors (Surmeier et al.,
1988). Of the low threshold mechanoreceptive cells in the
nucleus gracilis, 19% preferred static indentation over
brushing stimuli. The other two pathways contained too
small a number of such response types to be grouped
accordingly. Based on this population, it appears that
slowly adapting (SA) input may be routed predominantly
through the DC nuclei to the medial lemniscus. However,
investigations of afferent fiber sorting in fasciculus
gracilis have indicated that rapidly adapting (RA) primary
afferents project to nucleus gracilis in the DC, and SA
afferents project to the same target via the DL, after a
synapse in the dorsal horn (Whitsel et al., 1972; Brown,
1968).


62
complex between the normal and the DC-deafferented cortex
(p<0.05), but this was not true for the average of the
animals. It should be noted that, in monkey S, the
comparison between the sides was made after the DC lesion;
consequently, there was a partial DC lesion on the control
side of this animal.
The evoked potential recorded in response to
electrocutaneous stimulation of the ankle showed that
interruption of the DC led to a change in the amplitude of
both the p20-n50 and p90-n50 complexes. However, there was
no significant change in the slope of either frequency-
response function following the DC lesion, in contrast to
the results from electrocutaneous stimulation of the thenar
eminence of the foot.
Summary of Chronic Recordings. The awake recordings
showed that under all stimulus conditions there was a
statistically significant change in the amplitude of the
evoked potential following interruption of the DC. When
electrocutaneous stimulation to the sole of the foot was
used, there was a significant change in the frequency-
dependent suppression of the early response after a DC
lesion. This result was not observed under conditions of
mechanical stimulation of the foot or electrical stimulation
of the ankle.


Figure 3-10. Post-lesion evoked potentials in response to different
stimulus frequencies (monkey S). Solid lines represent 500 ms averages
of responses to frequencies from 1.5 to 10 pps (right of each trace).
From 1160 to 1239 averages were accumulated from recordings on 20 days.