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Generalization of Repetitive Rhythmic Bilateral Training

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GENERALIZATION OF REPETITIVE RHYTHMIC BILATERAL TRAINING By CLAUDIA ANN RUTTER SENESAC A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLOR IDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2006

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Copyright 2006 by Claudia Ann Rutter Senesac

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This document is dedicated Emily Salles Senesac, Robert Edward Senesac and in Memory of Ashley OMara Senes ac and Robert Basil Rutter

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iv ACKNOWLEDGMENTS I thank my family for their patience a nd understanding as I pursued a dream to learn more about the body and mind. With thei r love and encouragement I complete this journey and begin another.

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v TABLE OF CONTENTS page ACKNOWLEDGMENTS.................................................................................................iv LIST OF TABLES............................................................................................................vii LIST OF FIGURES.........................................................................................................viii LIST OF OBJECTS...........................................................................................................ix ABSTRACT....................................................................................................................... ..x CHAPTER 1 INTRODUCTION........................................................................................................1 Stroke and UE Rehabilitation.......................................................................................3 Theoretical Basis..........................................................................................................5 Neuroplasticity and Use-dependent Plasticity..............................................................6 Motor Learning.............................................................................................................9 Bilateral Training........................................................................................................14 Biomechanics of Reaching.........................................................................................18 Summary.....................................................................................................................19 Specific Aims......................................................................................................21 Research Aims and Hypotheses..........................................................................22 General aim 1...............................................................................................22 Specific aim 1a and 1b.................................................................................22 Primary hypotheses 1a and 1b for spatial parameter....................................22 Secondary hypotheses 2a and 2b for temporal parameters..........................23 2 METHODS.................................................................................................................25 Experimental Design..................................................................................................25 Subjects................................................................................................................25 Procedure....................................................................................................................26 Outcome Measures.....................................................................................................29 Kinematic analysis of reaching....................................................................29 Novel Task #1(Similar).......................................................................................30 Novel Task #2(Dissimilar)..................................................................................31 Primary Spatial Dependent Variable...................................................................32

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vi Secondary Temporal Dependent Variables.........................................................32 Posteriori of velocity profiles..............................................................................33 Data Analysis..............................................................................................................34 3 RESULTS...................................................................................................................36 Data Analysis..............................................................................................................36 Primary Spatial Dependent Variable...................................................................36 Hand path trajectory.....................................................................................37 Secondary Temporal Dependent Variables.........................................................37 Movement time............................................................................................37 Time to peak velocity...................................................................................38 Peak velocity.......................................................................................................38 Acceleration.................................................................................................39 Posteriori of velocity profiles..............................................................................39 Descriptive Individual Data........................................................................................39 4 DISCUSSION.............................................................................................................49 Neuroscience Rationale for Repeti tive Rhythmic Bilateral Training.........................51 Factors Potentially Aff ecting the Study Results.........................................................53 Summary.....................................................................................................................59 Limitations to the Study..............................................................................................60 Future Studies.............................................................................................................61 Conclusions.................................................................................................................62 LIST OF REFERENCES...................................................................................................64 BIOGRAPHICAL SKETCH.............................................................................................72

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vii LIST OF TABLES Table page 2-1 Demographic data....................................................................................................27 3-1 Means and standard deviations (sd) for all dependent variables .............................41 3-2 Summary ANOVA model for th e primary dependent variable...............................42 3-3 Summary of ANOVA m odel the secondary dependent variables............................42 3-4 Summary ANOVA model for posterior i analysis of velocity profiles.....................43 3-5 Summary of indi vidual change ...............................................................................44

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viii LIST OF FIGURES Figure page 2-1 Illustration of testing conditions for similar spatial orient ation novel task #1.........30 2-2 Illustration of testing conditions for di ssimilar spatial orient ation novel task #2....31 3-1 Significant main effect disp layed for HPT for post-test..........................................45 3-2 Significant main effect di splayed for MT2 novel task #1........................................46 3-3 Significant main effect disp layed for PV on the post-test........................................47 3-4 Significant main effect displa yed for posteriori Peaks Metric.................................48 4-1 BATRAC invariant features.....................................................................................55

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ix LIST OF OBJECTS Object page 2-1 BATRAC Inphase...................................................................................................29 2-2 BATRAC Antiphase...............................................................................................29 3-2 Testing conditions for generalization Pre-test..........................................................40 3-3 Testing conditions for generalization Post-test........................................................40

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x Abstract of Dissertation Pres ented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy GENERALIZATION OF REPETITIVE RHYTHMIC BILATERAL TRAINING By Claudia Ann Rutter Senesac May 2006 Chair: Lorie Richards Major Department: Rehabilitation Science Background and purpose: Bilateral training (BT) is an alternative approach in neurorehabilitation for individua ls post stroke. Bilateral training activities may increase the activity of the affected hemisphere and decrease the activity in the unaffected hemisphere providing a balancing effect between hemispheric corticomotorneuron excitability. One bilateral a pproach, repetitive rhythmic b ilateral training, developed and researched by Whitall, has shown improved mo tor function after intervention post stroke. Yet, an important question is whether this t ype of practice will result in improvements in untrained movements. The ability to pe rform related untrained motor tasks is generalization. The purpose of this study is to determine if repetitive rhythmic bilateral training will promote spatial ge neralization to a novel task. Methods: Fourteen participants with he miparesis completed the study. The intervention used an arm training machine BATRACconsisting of two paddles mounted in nearly frictionless tracks. The participan ts moved the handles back and forth in a rhythmic manner for 5-minute blocks. Half of th e blocks were in-phase ; the other half of

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xi the blocks were anti-phase. Practice sessi ons were 4 days/week, 2:25 hours/day, for 2 weeks, for a total of 18 hours of training. We measured movement time, time to peak velocity, hand path trajectory, peak velo city, and acceleration using the Vicon motion analysis system during 2 reaches to target ta sks preand posttraining. Each participant gave informed consent according to Universi ty of Florida Institutional Review Board and North Florida/South Georgia Subcommittee for Clinical Investigati on requirements prior to participation. Results: Improvements were found at post-test only for hand path trajectory and peak velocity. They were equivalent across similar and dissimilar tasks. Movement time 2 was less for novel task #1 compared to nove l task #2 but equivalent across preand posttesting periods. No in teraction effects were found. Conclusion: Unlike Whitall, our kinematic result s suggest that repetitive rhythmic BT alone is not sufficient to change motor cont rol, specifically generalization to similar, but untrained tasks. However, the small and heterogeneous study sample precludes definitive conclusions regarding the usefulne ss of this practice paradigm for promoting motor skills post-stroke.

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1 CHAPTER 1 INTRODUCTION Stroke strikes 700,000 persons each year in the United States resulting in varying degrees of permanent disablement.1 Many of the people affected by stroke will have a residual upper extremity (UE) motor and sensory deficit that will influence their ability to participate in life roles. These deficits typically involve decreased UE use and coordinative control of the arm and hand fo r activities of daily living, gesturing, and bilateral activities and will affect 78% of those individuals surviving stroke.2 Furthermore the vast majority of those with severe UE paresis will not recover full function of their arm and hand after 6-11 weeks of traditional therapy. 3 The effectiveness of current rehabilitation approaches for restorati on of UE function ha s not identified one intervention as being superior to ot hers in gaining function in the UE.3, 4 Scientific evidence now suggests that to enhance motor recovery post stroke, one of the critical components in an intervention protocol is practice.5, 6 Thus finding effective UE motor rehabilitative interventions is an important goal. Development of new, more effective rehabilitation techniques depends upon understanding the neural, physical and be havioral expression of movement.7 Specifically, an understanding of the CNSs ability to reco ver in the face of injury, and the extrinsic factors that can influence that recovery, is essential for successful neurorehabilitation. Key to motor recovery following stroke is th e CNS ability to learn or relearn motor behaviors. This recovery can occur spontan eously, or more likel y, will require practice of the lost motor abilities to facilita te reorganization of the motor cortex.5, 7, 8

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2 Re-training and practicing ev ery motor behavior that th e individual will be called upon to use in everyday life is unrealistic. Motor contro l theory suggests that all movement behaviors, or tasks, contain esse ntial features that can be entrained with practice.9 Motor learning theory further suggests that these features, once trained, can be transferred to another task that requires th e same features(s). This is called a generalization effect.9Taking advantage of this effect c ould have a significant impact on UE rehabilitation post-stroke. Bilateral training is an emerging approach in neurorehabilitation for individuals post-stroke. Bilateral movements form a tight phasic relationship organizing the behavior to perform as a functional synergy.9-11 Animal and human research has supported the notion that both hemispheres are active during bilateral activties.12-14 During the acquisition phase of learning a bi lateral skill, there is a func tional coupling of motor areas in both cerebral hemispheres.15 In persons post-stroke, bilate ral activities have increased activity of the damaged hemisphere and decrea sed activity in the undamaged to facilitate a more balanced effect of between-hemisphe re corticomotorneuron (CMN) excitability.16, 17 For example, repetitive bilateral arm traini ng increased activation in the contralesional cerebrum and ispsilesional cerebe llum after 18 hours of training.18 The response of the motor cortex to bilateral training with reorga nization is encouraging. Bilateral training may lay a foundation in individuals post st roke for engaging coordinative structures allowing the execution of basic motions and movement even though the practice is not real life task practice. The basic motions provided in bilateral training may entrain both hemispheres and provide the essential features necessary to generalize to similar tasks not specifically

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3 trained in the intervention. Generalization of a task should be optimal when the neural demands and conditions are similar.9 However, because functional tasks are not directly trained, test of the generaliza tion is important. The purpose of this study is to determine if repetitive bilateral training will promot e spatial generalizatio n to a novel task. The following literature review is composed of five main sections and will serve to orient the reader to foundation principles underlying the purpose a nd hypotheses of this project. The sections will in clude the following: 1) stroke and UE rehabilitation; 2) theoretical basis; 3) neuroplasticity and us e-dependent plasticity; 4) motor learning: practice and generalization, and 5) bilateral training in stroke rehabilitation. First, the traditional view of stroke and rehabilitation will be compared and contrasted with more recent views based upon new scientific evid ence. Second, conceptual frameworks for studying UE recovery following stroke will be reviewed. In the third section, basic elements of CNS neuroplasticity and training effects on CNS plasticity will be reviewed. Motor learning principles incl uding generalization, and prac tice and their relevance to stroke rehabilitation will then be discussed in the fourth section. Finally, the use of bilateral training incorporating key motor l earning principles will be discussed as a potential new therapeutic approach. Stroke and UE Rehabilitation Each year 700,000 persons will suffer a new or recurrent stroke in the United States resulting in varying degrees of permanent disablement.19 Many of the people affected by stroke will have a persistent upper extremity (UE) motor and sensory deficit that will influence their ability to participate in activit ies of daily living and life roles. Motor and sensory deficits typically i nvolve decreased coordinative movement of the arm and hand and UE use for activities encountered in a pe rsons daily environment including self-help

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4 skills, gesturing and bilateral activies.2 Furthermore, the vast majority of those with severe UE paresis will not recover complete function of their arm and hand after 6-11 weeks of traditional therapy. 3 In fact, use of the UE is so important that subjective measures of well being are directly related to perceived motor impairments of the arm affecting quality of life. 19 Thus, developing effective UE motor rehabilitative interventions is extraordinarily important, es pecially in light of current rehabilitative approaches to UE treatment that lack clear consensus, and are conflicted and unsubstantiated. 3, 4 Upper extremity interventions in the str oke population have historically focused on treatment of single limb moveme nts; treating the intact a nd affected arm separately.20-24 Methods designed to restore motor skill in the affected UE are influenced by facilitation models of motor recovery and emphasize ha ndling or guidance to achieve more normal movement patterns. Practice under these c onditions improves performance, but improved performance of a task does not necessarily le ad to relatively permanent changes, which characterize motor learning.7, 9 Performance during motor sk ill learning is a temporary change in behavior that is observed during practice sessions but may not be retrieved at a later time for execution.9 This may be because practice under traditional motor rehabilitative approaches allows for few erro rs, and little problem solving (by the learner) of the criteria inherent in the task.25 In addition many of these traditional therapy approaches were based on the hierarchical-r eflex theory, which has not held up under the scrutiny of the current motor control and mo tor learning literature. Nonetheless, these facilitory models continue to be used as traditional standard of care for rehabilitation.26-29

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5 Theoretical Basis The hierarchical-reflex model suggests that motor learning in rehabilitation is a stepwise sequence of motor recovery and moto r development from lower levels to higher levels of control.30 Treatment based on this theory of motor control often will focus on the movements that are most automatic requiri ng sensory stimulation from the therapist, progressing to more skilled voluntary tasks. This approach is often referred to as a traditional approach utilizing facilitation from the therapist to accomplish goals. New approaches to rehabilitation are beginni ng to surface based on the concepts of neuroplasticity and mo tor learning theories. Bernstein first proposed the systems theo ry in the early to mid 1900s although it was not incorporated into reha bilitation until the early 1980s. 9, 25, 31 Bernstein viewed the nervous system as one of many contri butors to movement execution but not the controller of movement. Move ments are seen as a result of an interaction among many systems including internal and external envi ronments, organized around behavioral goals with distributed control. Bernstein noted that there were many degr ees of freedom (df) available to produce a movement. Different df are characteristic of a task, environmental demands, and the performer. These df need to be controlled for effective movement to be accomplished. He purposed that the formation of synergies (groups of muscles a nd joints constrained together) could control the multiple df problem. This model can describe how learning of a new motor skill takes place. In the early st ages of learning a new task the movement may be simple. Movement at one joint may be allowed to vary with intermediate joints held stiffly utilizing cocontra ction of muscles to control th e df. Once the movement is learned muscle cocontraction is reduced and the movement becomes more fluid

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6 indicating the ability of th e central nervous system to use multiple resources to accomplish a task. In stroke, these synergie s are constrained in a pathological manner with stereotypical movements observed with attempts to move.21, 22 Difficulty is noted in the ability to control the multiple df that ar e available in the extremities and trunk. This inability to form normal synergies of move ment leads to compensation and decreased fluidity of movement in persons poststroke.24 Neuroplasticity and Use-dependent Plasticity Brain infarction results in a semi-revers ible set of pathophysiological events including swelling of the affected area, impair ed circulation and pyram idal cell injury or death.8 Recovery from brain infarction involves plasticitythe ability of the central nervous system to reorganize after brain injury. 32 Developing an understanding of the post-ischemic plasticity and its effect on motor control a nd motor learning has become the focus of current rehabilitative efforts.9 The CNS post-stroke begins a process of spontaneous recovery which involves neurol ogical reorganization. In contrast to individuals with intact nervous systems, attemp ts to move after stroke result in decreased activation in the affected motor cortex w ith increased activity in the non-affected hemisphere.8, 33, 34 These findings suggest even t hough crossed motor pathways are damaged, after stroke recruitment of preex isting uncrossed motor neural pathways may be accessed.34 Ipsilateral motor unit activity can be induced when the ipsilateral dorsal premotor cortex area is stimulated by TMS. This stimulation has demonstrated shorter latencies when compared to contralateral stimulation of the premotor cortex when the hand is moved in stroke patients.35 Even in individuals who have recovered from stroke, there is an increased activ ation of the CMN pool in the undamaged hemisphere when compared to persons with intact nerv ous systems performing a finger tapping

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7 movement.33, 36 However, recovery from stroke is associated with decreasing activation in the contralesional hemisphere and increas ing activation in the lesioned hemisphere; a more normal balance of activation is seen. Motor recovery post stroke is augmen ted by rehabilitation. Rehabilitation of individuals post-stroke involves motor learning. Motor learning is characterized by a set of processes that are associated with practi ce. These processes influence change in the internal state of the central nervous system and become relatively permanent, capable of being retrieved from long-term memory centers into working memory for motor execution.5, 7, 9 In the case of the individual with st roke, rehabilitation is concerned with the relearning of once familiar motor skills using new motor pathways. Coordinative patterns of movement must be practiced to create these new motor pathways during recovery for the execution of motor skills. The capability by which the brain modifies structure and function in re sponse to learning or brain damage is neuroplasticity.5, 7 Several mechanisms of reorganization of cor tical areas after stroke or brain injury have been proposed. Unmasking is a term used to indicate decreased inhibition of preexisting excitatory synapses allowing for functionally inactive connections to become active. Changes that are rapidly induced dur ing spontaneous recovery after injury are believed to be unmasking.5 Synaptogensis refers to growth of new neural connections and is related to environment and practice.8 Long term potentiation (LTP) involves the increasing sensitivity of synapses pre-synapt ically through constant stimulation with a resultant larger postsynaptic output. Long term potentiation and synaptogensis are believed to occur over longer time periods, coming into play dur ing intense practice.5 Sparing refers to the areas of the brain that were not damaged duri ng the injury and may

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8 be adjacent or interconnected to the damage d area. These areas of sparing have been shown to play a role in reor ganization of cortical maps.5, 37-39 Nudo et al. has demonstrated in a study with squirrel monkey s that the motor cortical areas of the brain can reorganize after brain injury.32 Further investigation by this group of researchers suggest that reorgani zation of cortical maps is dependent on rehabilitation and practice.38, 40-42 Use-dependent plasticity relies on activation of the brain during periods of practice. 5, 7 Calautti and Baron reviewed neuroimaging studies of individuals post-stroke and f ound reorganization of motor areas with enhanced activity in existing neural networks. In this revi ew, both motor training and pharmacological interventions were found to induce this incr eased activity in the damaged hemisphere associated with recovery of f unction and improved motor skills.43 Calautti and Baron observed significant changes in neuromapping in individuals involve d in intense practice of specific tasks. For example, neuroplastici ty associated with motor rehabilitation has been documented with the treatment paradi gm constraint-induced movement therapy (CIMT).44-46 Cortical reorganization in motor out put areas of the damaged hemisphere and in areas adjacent to the damaged site have been demonstrated as a result of intense practice. 37, 47, 48 Jang et al. demonstrated cortical reorganization by fMRI after 4 weeks (4 days/week, 40 minutes/day) of task orie nted training (pract icing of functional tasks). This training consiste d of six tasks to improve UE function in 4 individuals with chronic stroke. Cortical reorganization was ev ident with changes in the activation of the primary sensory motor cortex (decrease in ac tivation of the unaffected hemisphere and increase activation in the affected hemisphere).49 These studies indicate that practice is an

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9 important component of the moto r rehabilitative process as it facilitates neur oplasticity of the cortical motor areas. Motor Learning Motor learning and the underlying neur oplastic changes are dependent on practice. 5, 7 In the face of neuropathology, persons post-stroke must confront relearning skills that once were part of their daily routine. Determining the conditions for optimal learning in persons post-stroke require s an understanding of the different types of practice available during a reha bilitation program. The type of practice schedule that is selected during therapy has a strong effect on the process of motor learning effecting the basic components of movement and building th e specifics of coordi nation for activities.9 Certain principles of motor learning are well established in healthy adults but not well understood in stroke. Mass practice builds capacity (skillfulness, ab ility) by utilizing longer practice periods and short rest periods between trials. However, this type of practice can lead to fatigue resulting in detrimental results for act ual motor learning, transfer (generalization), and retention.9 Practicing under conditions of fatigue may affect the synergies that are engaged during the learning of the task, a nd ultimately the ability to retrieve the appropriate information for the execution of the task at a later time (retention and transfer) is reduced. Distributed practice provides shortened pract ice sessions and equal or longer rest periods than the actual task trials. This type of practice improves performance without the complication of fati gue and has demonstrated positive effects on motor learning as measured by transfer trials. 9 The sequence of practice is also an essent ial component to motor learning. Practice that repeats one task for a set number of tr ials before moving on to the next task is

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10 referred to as blocked practice This type of practice ha s low contextual interference (learning within the context of only one task) as the person lear ns the criteria for the task and performs several repetitions in the acqui sition phase before moving on to another skill. Blocked practice enhances performance but may be detrimental to retention or permanent learning as there is a low demand on problem solving once the criteria of the skill are understood. Blocked practice is used in therapy when the task is just being introduced and the participant is becoming fa miliar with the criteria of the movement. Random practice intermixes trials so that no task is repeated on two consecutive trials. The order of presentation of trials is va ried presenting a high degree of contextual interference (learning one task in the context of other ta sks). Random practice provides different patterns of coordina tion with different underlying motor programs with a range of solutions for motor tasks.50 This type of practice can be detrimental to performance during the acquisition phase but beneficial to motor lear ning and retention with the continual demand on retrieving the criteria of the task.51, 52 During rehabilitation, therapists attempt to help the indivi dual with stroke build the ability to produce coordinative movements. Because it is impossible during rehabilitation to practice every motor task the person will enco unter in daily activity, it is believed that the basic coordination gained by practicing some tasks during rehabilitation will generalize to unpracticed motor tasks the indi vidual will encounter in his/her everyday life. The concept of generaliza tion or transfer allows for the execution of other, related skills apart from the specific practiced task (new skill or new environment). 7, 9 The critical aspect of generalizat ion of a motor task appears to be whether similar neural processing requirements of the tasks are in corporated. The more closely linked the

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11 conditions and demands of the new skill or new environment are to the practice environment, the better the transfer.53, 54 This ability to retrieve information for retention and generalization is directly linked to practice and the type of invariant features that constitute the motor skill.9 Choosing the right practice schedule and sequence are dependent on the stage of learning that the individual is in and the clas sification of the motor skill that is to be practiced. When a person who is neurological ly intact is learni ng a new task he/she begins by gaining an understanding of the rule s and strategies inhere nt in performing the task. Systems theory suggest that learning the invariant features of the task is accomplished by engaging coordinative structures (muscles, joints, neural components, arousal, and gravitational influences).7, 31 The learning of a coordinative movement involves components of th e internal and external environm ent all of which contribute to the pattern of coordination that emerges. Skilled movements require parameters that make the task unique and different from othe r tasks. The unique features contain rules that are particular to that ta sk. Learning these rules and the in variant features of the task is often referred to as th e cognitive phase of learning.9 Each phase of learning allows for the complexity of the task to increase and the motor skill to be refined until it is automatic. In the early stages of recovery after st roke many people have difficulty initiating any movement. This lack of movement, re lated to a decrease of the CMN pool, makes activation and muscular recruitment a difficult task.55 Rehabilitation post stroke at this level is concerned with gaining an ability to move, learning the basic interjoint coordination and activation patte rn of muscles, which give s feedback about movement

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12 and how to recruit muscles for motor tasks. In persons post-stroke this stage of learning is coupled with building the physio logical capacity to move and is usually very cognitively demanding, requiring high levels of concentration. What do we know about practice and therapy intervention post-stroke? There are few studies examining motor practice paramete rs post-stroke. Many of the studies that are cited in the literature mention practice but fail to elaborate on the specifics of the practice conditions using traditional therapy as the intervention.27-29There are limited studies on UE practice protocols in stroke that have shown positive results paying attention to the specifics of pr actice. Some of these studies have demonstrated that some of the same principles of motor learning and practice as established in healthy individuals apply to motor learning post-stroke. Others have not. For example, Hanlon52 1996 studied 24 subjects with chronic hemiparesis to determine the effect of different practice schedules for the acquisition and retention of a functional movement sequence for the involved UE. Subjects were randomized into three groups: control, blocked, and random practice groups. The movement sequence involved a serial task that was alternated with trials on three other tasks in the random group. The movement sequence was practiced in two blocks of five trials in the blocke d group. A significant difference was found between random and blocked practice groups with ra ndom practice being more effective for retention over time in individuals post stroke.52 These results in the stroke population follow the principles of motor learning, re tention and transfer in healthy adults.9 In contrast, Cauraugh56 2003 compared blocked and random practice sequences combined with active neuromuscular stimula tion trials in subjects with stroke. The movements practiced included: wrist/finger extension, el bow extension, and shoulder

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13 abduction. The results indicated motor improve ment in both groups without a difference between the two practice sequences. This study did not support what we know about contextual interference associated with random practice in healthy individuals.56 It is difficult to compare these studies as they us ed different types of tasks. However, the results of these stud ies illustrate how little is known about the effects of practice protocols, type of task practiced, in comb ination with the level of recovery of the individual participating in pr actice. The rules for practice in individuals post stroke are unclear and the factors affecti ng the results of practice in this population have not been established.35 Are the concepts of motor le arning based on neurologically intact individuals relevant when persons post-str oke have difficulty initiating movement and use pathological synergies to accomplish the movements that they do execute? Principles of generalization post-stroke ha ve had even less science. First, lets examine what is known about generalization in healthy individuals in relation to UE movement tasks. Generaliza tion is an ability to execu te another motor task not specifically practiced. The ability to dissociate a learned moto r skill utilizing coordinative structures and features of the pr acticed task that are similar to but not part of the practiced task would be an example of genera lization. In a study by Sainburg et al.57 hand movement directions were reported to ge neralize for movements made up to 36 degrees to either side of the trained direction in individuals without neurological deficits. Generalization beyond the region of training has been documen ted successfully when a tight coupling of angle of gaze (visual field) and the position of the hand and shoulder are provided.58 In both studies, the nervous system de monstrated an ability to use sensory information to recalibrate the internal model formed by the practiced task. This

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14 recalibration allows for a limited amount of adaptation by the musculoskeletal system to a novel task. This agrees with our knowledge that the best genera lization occurs when the neural processing requirements are simila r to that of the pr acticed task. Which parameters of the task that are critical ar e not clear. Understanding the parameters that enhance generalization following stroke can contribute to the design of treatment protocols. Acquiring interventions that would generalize to skills not specifically trained in practice sessions (trials) woul d be advantageous therapeutic ally. Identifying particular intervention protocols and pairi ng them with the stage of recovery or learning that the individual may be in could e nhance their rehabilitation. By building capacity early on in recovery and layering more complex skills as individuals post-stroke gain an ability to move could lessen their overall UE disablemen t. Introducing the right intervention at the right time may enhance motor lear ning, retention and generalization. Bilateral Training A new approach to UE stroke rehabilitation; bilateral training is beginning to be investigated systematically and demonstrating some positive results. 16, 59-62 Protocols in these studies have used functional and non-f unctional tasks practiced bilaterally with similar temporal and spatial requirements.60, 61, 63 What do we know about the brain and bimanual coordination? Researchers believe that bilateral trai ning may be a good approach in stroke rehabilitation based on what we know a bout the brain and bimanual coordination. Bilateral movements form a tight phasic re lationship causing them to perform as a functional synergy.10, 11The establishment of such coordina tive structures during bilateral movement may serve as a template and en train the paretic arm during the movement

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15 phase with the uninvolved hemi sphere providing a pattern of firing for the involved hemisphere.64 Generalization of task performance fr om one arm to the other is not a new concept. For example, reaching movements generalize from the dominant arm to the non-dominant arm in healthy individuals.65 How does reaching with one arm improve function in the contralateral arm? When le arning the dynamics of a reaching task the neural representation for the dominant arm in the contralateral hemisphere may engage neural elements for both arms. To assess the dependence of gene ralization on callosal inter-hemispheric communication, Criscimagna-Hemminger et al.65 further investigated transfer of the dominant UE to the non-domin ant UE in a person with a commissurotomy. The results were similar with generaliz ation from dominant to nondominant arm (unaffected UE to affected UE).65 What is the relationship to individuals with stroke? Conceivably bilateral training may have a sim ilar effect on individuals post-stroke with improved transfer from the uni nvolved UE to the affected UE. Bilateral practice may also be beneficial because both hemisphere s are active during bilateral actions perhaps activating uncrossed tracts.12-14, 34, 35, 66 Evidence from animal and human research supports the notion that a temporal interacti on between hemispheres occurs in the motor cortex. Gerloff et al.15 reviewed the functional coupling of the motor areas of both cerebral hemispheres during bilateral learning. Inte rhemispheric interaction is particularly important during the acquisition phase of the skill.15 Bilateral training may be an appropriate starting place for re habilitation after stroke. There are three studies using repetitive rhythmic bilateral training which have demonstrated some transfer effects to other tasks incorporating specific critical elements

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16 of the original training task. In these studies training involve d non-functional tasks performed bilaterally with similar spatial and temporal parameters for each extremity using rhythmic synchronized inphase and an tiphase movements. However, many of the bimanual tasks that are used in daily lif e require a different contribution from each extremity. Thus, it is critical to show generalization of this type of training to other useful coordinative patterns utilized in daily activit ies as our arms are not always performing with similar patterns of movement. One of the missing components to our understanding of this intervention in stroke is ge neralization of the bilateral training. The Whitall, et al.61study investigated the hypothesis that bilateral upper extremity training with auditory cueing of a metronom e would improve motor function in persons who had suffered from stroke. The interven tion involved a custom designed arm-training machine (BATRAC-bilateral arm training with rhythmic auditory cu eing), which allowed for elbow and shoulder flexion and extension coordinated to a metr onome set at a selfselected speed. This study concentrated on a proximal effector system involving shoulder and elbow joints while limiting trunk forward lean during reaching by a chest restraint. The design was a single group pilot study with 14 subjects consisting of 20minute training sessions, 3 times per week for a 6-week period of intervention with a total of 18 sessions. Each session consisted of four 5-minute periods alternating inphase and antiphase movements using the BATRAC inters persed with 10-minute rest periods for distributed practice. Results indicated signi ficant improvement in motor performance on the Fugl Meyer (FM) upper extremity sect ion, significant improvement in performance time on the Wolf Motor Function Test (WMFT) and significant increas e in daily use of

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17 the affected extremity on the Maryland Arm Questionnaire for Stroke after six weeks of training with sustained improvement at 8 weeks after training cessation. 61 In a follow-up study, fMRI demonstrated increased hemispheric activation during paretic arm movement with changes in th e contralesional cortex and ipsilesional cerebellum after training utilizing the BATRAC.18 Cerebellar activity has been identified as a principal region for the c ontrol of bimanual coordination.14 Although the numbers of subjects (6) who demonstrated changes in the Luft et al.18 study are small, it is encouraging data that supports repetitive bilateral training. Bila teral training as a potential therapeutic intervention has been bolstered by evidence of reorganization of the motor cortex in individuals usi ng BATRAC post stroke. Stinear and Byblow 16 had individuals with stroke perform active movement of the unaffected wrist, which drove passive wr ist flexion-extension of the affected UE using a manipuladum at a self-paced rhythm. Focus was placed on the distal effector system, the wrist joint. Nine subjects of a heterogeneous group of stroke participants practiced for 60 minutes a day for a total of 4 weeks with a random assignment into groups of synchronous and asynchronous practic e. Five of the nine participants demonstrated improvement in motricity scor es as measured by the wrist, hand and coordination components of the upper limb s ection of the FM Assessment of Motor Function. Postintervention transcranial magne tic stimulation (TMS) revealed a decrease in the unaffected cortical ma p volume in the subgroup of fi ve patients that improved in motricity. The subjects that demonstrated si gnificant results were a mix of persons with cortical and subcortical lesions acute and chronic stroke, mild and severe disability, and had a combination of synchronous and asynchro nous training. The results of this study

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18 suggest that bilateral traini ng promotes a balancing of between-hemisphere corticomotor excitablility.16 Although these studies have suggested th at motor learning has occurred after bilateral training they have not delineated the parameters or limits of motor skill generalization with this practice. Schmidt9 suggests that the more similar the neural demands are during novel tasks the greater the transfer.54 Specifics of the basic neural elements involved in repetitive bilateral trai ning for individuals post-stroke have not been assessed in a transfer test. There are only a couple of st udies on bilateral coordination that delineated parameters important for genera lization of a novel task in individuals who were neurologically intact.67, 68 Little is known about the pr inciples of generalization of bilateral coordination in healthy individuals except the studies mentioned above and to date there is nothing in the literature involving the stroke population. In neurologically intact individuals Temprado and Swinnen demonstrated generalization of a bilateral coordinati on pattern to a novel pattern when the spatial relative phase (RP) (a variable that characterizes the spatial relationship between two limbs) of the transfer task was similar but not to a task with a different spatial RP.67 Muscle synergies engaged during interlimb coordination tasks are influenced by spatial orientation. The sy mmetry of movement may be an important factor in improving coordi nation in bilateral tasks.68 Determining the relationship of training task parameters (spatial, angle of gaze, joint angles) to generalization in individuals post stroke has not been specifically investigated. Biomechanics of Reaching Reaching is a functional task that requir es control of multiple joints through space.69 Kinematic measures of reaching have been utilized in studies of generalization to

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19 document change in the pattern of reaching.58, 67, 70 Biomechanical evaluations are capable of capturing interjoint coordinati on, and movement composition thus indicating quality of the reaching pattern.69, 71, 72 Biomechanical measures assessing temporal aspects of reaching include but are not limited to; movement time, time to peak velocity, peak velocity which indicates symmetry of the reach, strategy for reaching, and acceleration. Kinematic spatial parameters of reaching include hand path trajectory (how straight is the path to the target) during the reach.71 The literature on the biomechanics of reaching has documented that reaching post-stro ke is slower, discontinuous with many movement reversals (stops and starts duri ng the movement to th e target), and the trajectories are curved to the target.69, 71-73 Reliability and validity of these biomechanical measures in the stroke populati on are not established to date.71 However biomechanical assessment of reaching may provide an understa nding of motor control and assist in the evaluation of new therapies. Summary Motor learning and neuroplasticity are de pendent on practice. The appropriate type, duration, intensity, and frequency of practice to enhance motor learning, generalizability, and motor recovery have yet to be determined in the stroke population. What parameters should be emphasized in rehabilitation during practice sessions to maximize generalization? It is not clear if task specific trai ning is important in laying a foundation for coordinative movement in pers ons after stroke. Persons post stroke have difficulty moving and must relearn coordinativ e patterns to execute motor tasks. Perhaps the focus should be on engaging coordinative structures that might provide a general motor template to build physio logical capacity and complex movements. Establishing a motor capacity to move post stroke may provi de the framework for generalization of a

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20 practiced task. Supportive ev idence on bilateral training a nd generalization suggests that engaging similar spatial and temporal synergies may have positive effects on motor learning in persons post stroke.16, 18, 61, 63, 67, 68, 70 Utilizing Whitalls protocol for repetitiv e bilateral training: can a general framework of coordinative s ynergies be created divorced from a particular skill or task that would underlie the basics of motion a nd movement capabilities? Whitalls protocol used an arm training machine (BATRAC) for repetitive bilateral training in one orientation with inphase and out-phase moveme nts. The repetitive movement of the UEs in this protocol engages similar synergie s as real life reaching tasks bilaterally accomplished in the workspace directly in fron t of the person. Stinear and Byblow using a distal effector system demonstrated a balancing effect between hemispheres of corticomotor excitability. How functional is repetitive bilateral training and to what degree if any will this type of training assist an individual with stroke to execute tasks that were not specifically trained but similar? Therapy interventions have focused on simu lation of tasks that would be performed in the home and community. Therapists ha ve emphasized buildi ng a repertoire of movement skills that incorporate compone nts necessary for other unpracticed motor skills. Practicing every task that will be encountered by an individual once they are discharged from rehabilitation is impossibl e. Identifying interven tion protocols that generalize to tasks unpracticed in the rehabilita tion arena is essentia l. Generalization of learned motor skills would enhance a persons ab ility to participate in life roles at home and in the community by increasing the number of conditions and solutions to a host of motor problems. Bilateral training may lay a foundation in indivi duals post-stroke for

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21 engaging coordinative struct ures allowing the executi on of basic motions and movement even though the practice is not vari able or with real life tasks. Collecting kinematic data for assessment of generalizati on of this training may help us to understand which reach parameters might change after bi lateral training. Repetitive bilateral training is distributed blocked practice, which avoids fatigue but allows for the criteria of the skill to be learned without buildi ng endurance. This combina tion of practice may build a physiological capacity for movement in pe rsons post-stroke. The entrainment of both hemispheres during bilateral training provides a functional coupling of the motor cortexes especially during the acquisition ph ase of learning a bilateral task.15 Yet, the ability of such training to transfer to functional tasks awaits testing. The aim of this study is to determine if repetitive rhythmic bilateral training (using the BATRAC as outlined in the Whitall et al.61 study) will generalize to a novel task that is performed with similar neural demands. Specific Aims To test the hypotheses that repetitive bilatera l training using blocked-distributed practice will demonstrate spatial generaliza tion to a novel task with similar neural demands in joint angles, workspace, visu al gaze angles, and muscle timing. The following research questions will be addre ssed in a single group repeated measures design employing a pre-test and post-test peri od. Outcome measures will be taken prior to intervention and at the end (c ompletion) of 2 weeks of proximal repetitive bilateral intervention.

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22 Research Aims and Hypotheses General aim 1 To determine spatial generalization to a nove l task after proximal bilateral training for the affected upper extremity. Specific aim 1a and 1b 1a. To determine if proximal bilateral tr aining generalizes to a novel task (#1) that is similar in shoulder/elbow joint angles, cons traints of muscles and joints (coordination), visual gaze angles and a work space identical to the training. 1b. A secondary novel task (#2) will be test ed with different joint angles, visual gaze angles and workspace from the training motion. Primary hypotheses 1a and 1b for spatial parameter 1a. Generalization will occur fo r novel task (#1) when tested in the same workspace with similar joint angles as practiced for the proximal bila teral training intervention. At the end of week two of proxima l bilateral training: kinematic data for hand path trajectory to the target. will demonstrate generalization for novel task (#1 ). Data will be compared to baseline data with improvement for th e above kinematic outcome predicted. Hand paths to the target in stroke ar e variable and lack continuity..69, 71, 72 Therefore, based on the literature hand path trajec tory will be straighter. 1b. Gene ralization will not occur for novel task (#2) that is dissimilar in joint angl es and workspace to training. At the end of week two of proximal bilateral training: kine matic data for hand path trajectory will not generalize for novel task (2#) Data will be compared to baseline data with no improvement for the above kinematic outcome predicted.

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23 Secondary hypotheses 2a and 2b for temporal parameters Temporal parameters are assessed separa tely in this study because neither the training nor the testing tasks emphasized sp eed. Therefore these parameters may not change. Individuals post-stroke do move slow er when compared to healthy individuals so it is possible that the speed may be di fferent after interven tion although it was not emphasized.69 2a. Improvement in movement time, time to peak velocity, peak velocity and acceleration will occur for novel task (#1) when tested in the same workspace with similar joint angles as practiced for the pr oximal bilateral training intervention. At the end of week two of proximal bilateral training: kinematic data for movement time, time to peak velocity, peak velocity and acceler ation (the percent of the reach that is acceleration) will change. Data will be compar ed to baseline data with improvement for the above kinematic outcomes predicted. Indi viduals post-stroke move slower during reaching and often demonstrate a skewed prof ile in reaching with a shorter relative duration in the acceleration phase, peak veloc ity is often lower compared to healthy individuals and absolu te time to peak velocity is shorter.69, 71Therefore, based on the literature movement time will decrease, time to peak velocity will increase, peak velocity will be higher and the percentage of reach that is acceleration will approach 50% of the acceleration curve. 2b. Improvement in movement time, time to peak velocity, peak velocity, and acceleration will not occur for nove l task (#2) that is dissimilar in joint angles and workspace to training. At the end of week tw o of proximal bilateral training: kinematic data for movement time, time to peak velo city, peak velocity, and acceleration (the percentage of the reach that is acceleration) will not change for novel task #2. Data will

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24 be compared to baseline data with no im provement for the above kinematic outcomes predicted. Movement time, time to peak veloc ity, peak velocity, and the percentage of reach that is acceleration will not improve.

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25 CHAPTER 2 METHODS Experimental Design This study employed a single group, repeated measures design that included a pretest baseline and post-testing at the comp letion of two weeks of proximal bilateral training. Subjects Fifteen participants with hemiparesis and UE motor deficits were recruited from the Brain Rehabilitation Research Centers st roke database at th e North Florida/South Georgia Veterans Health System. One subjec t dropped out of the study due to unrelated medical reasons. This database consists of individuals with stroke who have been recruited to participate in rehabilitation studies from the North Florida/South Georgia VA, Shands Hospital at the University of Flor ida, Shands Rehabilita tion Hospital, Shands Hospital at Jacksonville, Brooks Rehabilita tion Hospital and the Brooks Center for Rehabilitation Studies in Jacksonville. Nine of the subjects were male and 5 were female with a mean age of 64.4 (sd = 13.3) years and a mean of 5.5 (sd = 3.9) years post-stroke. Five of participants had right -sided lesions and nine had le ft-sided lesions. Demographic and clinical data for the subjects are summarized in Table 2-1. Whitall1, Luft,2 and Stinear and Byblow3 all demonstrated treatment eff ects with sample sizes of 9-14 subjects. Inclusion criteria were: 1) single unilatera l stroke at least 6 months prior, 2) no active drug or alcohol abuse, 3) able to follow 2-step commands, 4) no history of a

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26 clinical ischemic or hemorrhagic event aff ecting the other hemisphere, and no CT or MRI evidence of more than a lacune or minor ischemic demyelination affecting the other hemisphere, 5) no history of more than mi nor head trauma, subarachnoid hemorrhage, dementia, learning disorder, drug or alcohol abuse, schizophreni a, serious medi cal illness, or refractory depression, 6) some active move ment in shoulder and elbow with palpable extrinsic forearm finger muscle recruitment. Exclusion criteria: 1) no movement in UE or no palpable muscle recruitment in extrinsic finger extensor muscles, 2) scores > 3 on the Motor Activity Log, i ndicating a high level of UE function, 3) spas ticity greater than 2 on the Modified Ashworth Scale. Each participant gave informed consen t according to University of Florida Institutional Review Board a nd North Florida/South Georgi a Subcommittee for Clinical Investigation requirements prior to participation. Procedure UE motor function for novel ta sk (#1) and (#2) was tested at the beginning of the baseline period prior to inte rvention and after two weeks of proximal bilateral training. All participants performed a session of baselin e testing immediately prior to starting the intervention (see Outcome Measures section below). The two-week intervention period was followed immediately by post-testing of UE generalization of training to a novel task. As in Whitall et al.,1 training was provided for 18 hours. However believing that intensity is important,4-6 these hours were provided in 8 sessions of 2.25 hours each across 2 weeks for a total of 18 hours. Shor t term upper extremity practice has been shown to be effective in improving upper extremity motor function in persons poststroke.7, 8

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27 Table 2-1. Subject demographic data Subject Age (years) sd = 13.3 Gender Years poststroke sd = 3.9 Side of Lesion Lesion site Fugl-Meyer* Pre 1 80 M 1 L CVA L MCA, parietal/post frontal 24 2 49 M 1 L CVA L subcortical infarct w/ hemorrhage conversion-basal ganglia internal capsule 51 3 80 F 3.5 R CVA R MCA hemorrhage, hematoma R basal ganglia 48 4 59 M 7.4 R CVA R MCA ischemic event 33 5 62 M 5.4 R CVA R MCA posterior 51 6 68 M 11 R CVA R cortical infarct 46 7 40 F 5.5 L CVA L putamen hemorrhage 37 8 72 M 11.3 L CVA L MCA posterior infarct 59 9 67 F 4.7 R CVA R superior hyrus, striatocapsular infarct 64 10 67 M 4.8 L CVA L frontal lobe hemorrhage w/atrophy 52 11 80 M 1.7 L CVA L subcortical lacunar periventicular 43 12 38 F 1.8 L CVA L MCA infarct, deep white matter insula frontal lobe, cortex F/P junction 35 13 64 F 3.8 L CVA L infarct insula F/Temp/P convexity 18 14 75 M 13.5 L CVA L MCA infarct 33 *Based on Fugl-Meyer scale (maximum score) =66, CVA= cerebrovascular accident

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28 Proximal bilateral training: The proximal bilateral exercise was identical to that performed in the study by Whitall and colleagues.1 In this paradigm, participants were seated facing a table on which was placed the arm training machine-BATRAC consisting of two paddles mounted in nearly frictionless tracks.1 The handles of the device are horizontally oriented and cylindr ical in shape. The participants grab the handles of the paddles (with the affected hand strapped on as needed) and move the handles back and forth in a rhythmic manner for 5-minute bloc ks with 10-minute breaks between blocks to minimize fatigue. There was a chest plate that prevented the participant from leaning forward with trunk flexion when the handles were pushed away from the persons body. This chest plate was set at a distance of six inches from the table and the participant was asked to keep his/her trunk against this plat e during the intervention periods. The distal stop on the BATRAC was lined up to the me tacarpalphangeal joint (MCP) when the intact arm and fingers were extended directly in front of the body over the track. This corresponded to 80% of the reach. When activ e range of motion was limited at the elbow joint the distal stop on the BATR AC was set at the wrist join t initially and progressed to the MCP joint the second week. For half of the blocks, the participants moved the handles symmetrically (in-phase); while in the other half of the bloc ks the participants moved the handles 180 out of phase. These trials were alternated and balanced across subjects and sessions. Because movement of one paddle is independent of the other paddle, participants had to coordinate the m ovements of both UEs in order to achieve the correct temporal and spatial movement relati onships. Participants were encouraged to move the full range of the exerciser and were assisted as needed by the researchers. Participants were asked to assume a comforta ble self paced movement speed at the first

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29 session, which was maintained throughout th e daily training session with the use of auditory cues provided by a metronome se t at the self-selected frequency. The metronome was set at the beginning of each day of training to the participants comfortable pace to prevent holding the individual back from making progress. Object 2-1. BATRAC Inphase. Object 2-2. BATRAC Antiphase Outcome Measures The primary hypothesis stated that in indi viduals with chroni c stroke, bilateral training would generalize to a novel task that was similar in neural demands to the training but not to the dissimilar novel task. The dependent va riables were divided into primary and secondary based on differences in spatial and temporal parameters. Knowing from the literature that movements in th e upper extremity are affected by abnormal synergies post-stroke, we believed that th e intervention (synchr onous and alternating movements bilaterally) would effect the spatial parameter to a greater extent than temporal parameters by breaking up the abnormal synergies through more normal interlimb coupling.8, 9 Therefore, the primary goal was to assess spatial generalization after bilateral training. The primary spatial dependent variable was HPT. The secondary hypothesis stated that bilatera l training would improve the temporal dependent variables (MT1, MT2, TPV, PV and acceleration) after 2 weeks of intervention. The procedures for testing preand post-intervention follow. Kinematic analysis of reaching Participants were seated on a bench with the hip and knee angle at 90 degrees and the feet flat on the floor. Each participant was asked to position their buttocks and back against a straight edge held behind them to assure the same start position on the bench

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30 each testing period. The affected UE was positione d at rest, palm down, on a table placed in front of the person at the same distance as the intervention table including the chest plate distance of six inches. The UE was in neutral shoulder flexion/extension, rotation and adducted. The elbow was flexed as in the start position for the arm-training machine. Novel Task #1(Similar) The start position on a table in front of them was identical to the start position used for the training with the BATRAC howeve r the arm-training machine was not used during novel task #1 nor was there a chest restra int. End targets at approximately 80% of reach were marked on the table at the same ar m reach length (elbow extension in front of the body as measured to the metacarpalphalange al joint or wrist joint determined during intervention) as in the arm-training machin e (BATRAC). A reflective marker was placed on the target so the vicon motion analysis system could pick up the end point. Participants moved their arm a nd hand to the target and return ed to the start position five times (Figure 2-1). The particip ants were not asked to point to the target but to simple reach to the target. To minimize fatigue, there was a 30 second rest break between reaches. Figure 2-1. Illustration of te sting conditions for similar sp atial orientation novel task #1 (similar task)

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31 Novel Task #2(Dissimilar) The start position was on a table aligned with the paretic shoulder directly in front of the subjects body at the same distance from the trunk as in the BATRAC during intervention. The subjects were asked to move their arm and hand to a target on the table that was aligned horizontally with the start position and with the non-paretic shoulder at the near edge of the table and then return to the start position five times (Figure 2-2). A reflective marker was used so that the vic on motion analysis system could pick up the end point. There was no trunk restraint used during this testing condition. To minimize fatigue, there was a 30 second rest break between reaches. Figure 2-2. Illustration of te sting conditions for dissimilar spatial orientat ion novel task #2 (dissimilar task) Kinematics of reaches were videotaped us ing a 3-D movement recording system (8 camera Vicon system). Retro-refl ective markers were placed on C7 and T10 vertebrae, the acromion process, clavicle, sternum, upper arm, lateral epicondyle of the elbow, medial epicondyle of the affected UE, forearm, wris t condyles, dorsum of the hand, MCP joint of

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32 the index finger, and the index fingertip of th e affected UE. The data was collected at 100 Hz. All data was averaged using th e middle 3 trials for each novel task. Kinematics were analyzed for hand path trajectories (end point paths measuring straightness of the hand path), movement time, time to peak velocity, peak velocity and acceleration as in Cirstea, et al., Cunningham et al., and McCrea et al.9-12 Posteriori analysis of the velocity pr ofiles to assess movement smoothness changes were performed as described by Rohrer et al.13 Primary Spatial Dependent Variable 1. To determine hand path trajectory (HPT), the ratio of the length of the actual path traveled by the index finger in three-dimensi onal space to the length of an ideal straight line joining the initial and final index finger positions was computed. If the participant was unable to extend the index finger, the traj ectory was measured from a marker on the metacarpalphalangeal joint of the 2nd digit. The length index rather than the more usual perpendicular distance between the trajectory be tter captures trajector ies that may deviate from the ideal straight line and may even inte rsect with that ideal line. Reach accuracy was computed as the root mean squared erro r of the absolute distance between the final endpoint position and the position of the target Secondary Temporal Dependent Variables Temporal parameters in reaching post-stro ke are significantly slower than healthy adults.10-12 Therefore, although subjects were not asked to reach as quickly as possible during the testing tasks, the predictions ar e based on the assumption that the training intervention would increase their usual speed. 1. Movement time was the difference in time from movement onset to movement offset. Movement time 1 (MT1) was defined as the onset of movement from the start

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33 position to the touch of the target. A mark wa s made with tape to delineate the start position and target area based on the interven tion position of the BATRAC arm-training machine. Movement time 2 (MT2) was defined as the movement onset from the target back to the start position. 2. Time to peak velocity (TPV) was a measure of absolute time measured in seconds from the point of movement onset to peak velocity. 3. Peak velocity (PV) corresponds to a moment in time when the highest velocity is reached where acceleration is at or near zero at the changeover from the acceleration to the deceleration phase. PV is calculated from the rate of change over time. 4. Acceleration was calculated from the slope or in clination of the velocity curve and includes the percent of reach within this curve. Accelerat ion corresponds with the time period of movement onset to peak velocity. Posteriori of velocity profiles The following metrics were analyzed poste riori to assess the movement smoothness of the velocity profiles during the no vel reaching task preand post-test. 1. Jerk metric was calculated from the average value of the absolute jerk divided by the peak velocity of the co rresponding trial (Jerk is define d as the rate of change of acceleration). Jerk metric is assigned a negati ve value so as the smoothness increases, the jerk metric also increases. 2. Speed metric was calculated from the average velocity divided by the peak velocity of the corresponding trial. As the smoothness increases, speed metric also increases. 3. Movement arrest period ratio (MAPR) was the amount of time that the velocity profile was less than 10% of the peak velocity divided by total time of the trial. A smaller MAPR indicates a smoother velocity profile.

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34 4. Peaks metric was the number of peaks in th e velocity profile greater than 0.5m/s multiplied by negative 1. As the smoothness increases, the peaks metric increases. 5. Tent metric was calculated from the area under the velocity profile curve divided by the area of a curve drap ed over the top of it. The closer tent metric is to 1, the smoother the velocity profile. Data storage conformed to HIPAA regulat ions. VICON-captured data was stored in a database on a secure network. Participan ts were assigned a participant number and this number was the only identifier stored on th ese databases. A list of the participants names and participant numbers wa s kept in a locked file in Dr Lorie Richards office. Only the investigator and Dr Richards had access to this list. Only study personnel had access to the participant notebooks or the database. Data Analysis For each dependent variable a repeated measures 2 (time) x 2 (task) ANOVA was performed with an alpha le vel of .05. Greenhouse-Geissers adjustment of degrees of freedom was applied to correct for small departures from the assumption of normality and equality of variance in the two-factor design. A Bonfe rroni correction factor was used to correct for multiple analyzes for the primary and secondary dependent variables. The corrected alpha level for the primar y dependent variables was .05, secondary dependent variables was .01, and .01 for the posteri ori analysis of the metrics. Lastly, a descriptive analysis of the individual data was performed post-hoc. The sample of this study was made up of a heterogeneous group of individuals with various levels of severity at baseline; therefore we decided to examine the data descriptively at the individual level, conjectur ing that this could provid e information on subgroups of

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35 individuals that may have be nefited, but would not have been detected in the group analyses.

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CHAPTER 3 RESULTS Data Analysis Kinematic outcomes were analyzed with a repeated measure ANOVA for each of the primary dependent variables. The within subjects factors were time (pre-test/post-test) and task condition (novel task #1 and novel task #2). The primary dependent variable was hand path trajectory. The sec ondary dependent variables were : 1) movement time, 2) time to peak velocity, 4) peak velocity and 5) the percentage of the reach that was acceleration. An alpha value was set at .05 and corrected with Bonferroni to account for multiple analyses on the secondary and posteriori analysis. The corrected alpha levels on dependent variables were .01 for the secondary and the posteriori analysis of the velocity profiles. Individual data will be reported last to identify individual differences that may account for a pattern in the data. Primary Spatial Dependent Variable Table 3-1 displays the means and standard deviations for all outcome measures for primary and secondary dependent variable s. Table 3-2 displays the ANOVA summary table. Hypothesis 1a and 1b HPT will become straighter af ter intervention for novel task #1 (generalization of similar ta sk). No change will be note d for HPT on novel task #2 (no generalization to dissimilar task).

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37 Hand path trajectory HPT was calculated as the ratio of the actual path traveled to the ideal straight line joining the initial and final positions for the index finger or metacarp alphalangeal joint of the 2nd digit (when subjects could not extend th e index finger). There was a significant main effect of time for HPT with hand path traj ectories straighter at posttest (Figure 3-1). However, there was no main effect of task nor interaction between the two variables. The increase in straightness was found for both novel task #1 and novel task #2. Therefore control of the spatial parameters of reach gained with interventi on generalized to both similar and dissimilar tasks. Secondary Temporal Dependent Variables The main effects are reported below and m eans and sd are displayed in Table 3-1. The ANOVA summary table for the secondary depend ent variables is displayed in Table 3-3. Hypothesis 2a and 2b Generalization to novel task #1 following intervention will be evident with decreased movement times. No improvement in movement times will be demonstrated on novel task #2. Movement time Contrary to expectations, the time to t ouch the target (MT1) was not significantly different post compared to pr e-intervention, nor across task s. MT2, although shorter for novel task #1 compared to novel task #2, al so did not change with intervention (Figure 3-2). There were no si gnificant interaction effects of time and task on either variables. The data for MT1 and MT2 did not suppor t the hypothesis that there would be improvement in motor control on an untrained task with similar joint angles to the training task. Movement time at post-test wa s no shorter than at pre-test. Bilateral

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38 training did not appear to im prove motor control during the performance of a task that was similar in terms of joint angles to the training task. Not surprisingly, no improvements in movement time were found for novel task #2, a task with dissimilar joint angles to the training task wh ich was in support of the hypothesis. Hypothesis 2a and 2b TPV will increase for novel task #1 following intervention: TPV will not change with novel task #2. Time to peak velocity TPV was measured from the point of move ment onset to peak velocity. There was no difference in TPV across time or tasks. Ther e were no significant interaction effects. Therefore, the training had no effect on the TPV. Hypothesis 2a and 2b: PV will increase for novel task #1 and will not change for novel task #2 following 2 weeks of intervention. Peak velocity PV was the highest velocity that occurred dur ing the reach. It typi cally occurs at the moment of changeover from acceleration to de celeration in reaching to a target. There was a significant main effect of time for PV (Figure 3-3) with PV larger following intervention for both novel tasks. There was no main effect of task nor interaction between time and task. Therefore, generali zation of training was seen for similar and dissimilar tasks. Hypothesis 2a and 2b The acceleration phase of the reach will approach 50% of the curve for novel task #1 and will not ch ange for novel task #2 following 2 weeks of intervention.

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39 Acceleration There were no main effects or interaction effects noted fo r percentage of the reach in acceleration. Posteriori of velocity profiles Although this analysis was performed poste riori, changes in the smoothness of the velocity curve could be beneficial in interp reting data collected on the reaching pattern of individuals post stroke. An AN OVA summary table for the post hoc analysis is displayed in Table 3-4. Changes in the metrics of the velocity pr ofile would point toward a smoothing of the velocity curve following intervention indicat ing fewer stops and starts in the reaching pattern toward the target. Smoothness of the curve would infer that the coordination of the motor pattern for reaching has improved. Th ere was a significant main effect of time for the Peaks Metric with improvement postintervention however no main or interaction effects for task (Figure 3-4). In addition, ther e were no main or interaction effects for the remaining smoothness metrics. Descriptive Individual Data Although this analysis is posteriori, this individual data could be beneficial in planning future trials. Table 3-5 displays th e individual data patte rn of change across primary and secondary variables for each subject. Individual differences were analyzed comp aring the raw score difference from preto post-test with the pre-test sd for each dependent variab le. Individuals who demonstrated a change at post-test greater th an the sd for the dependent variables at pretest are reported below. No subject improved in all variables with intervention. Interestingly in three of fourteen subject s no change for any dependent variable was

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40 noted and 4/14 subjects demonstrated a change in only one dependent variable. Five of fourteen subjects demonstrated differences grea ter than the sd of the pre-test on three or more variables. Thus, the de scriptive individual data s hows no general pattern across subjects or subsets of subjects. Training did not frequently foster change in similar tasks (novel task #1), but sometimes did in dissimila r tasks (novel task #2). In actuality change was infrequent across the board. Object 3-2. Testing conditions for generalization indicated some individuals changed. Pre-test. Object 3-3. Testing conditions for generalization indicated so me individuals changed Post-test

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41 Table 3-1. Displays the means and standard de viations (sd) for task condition # 1 and #2 for all dependent variables preand post-intervention. Task #1 Task #2 Similar Dissimilar Mean (sd) Mean (sd) HPT Pre Post 1.500 (.348) 1.519 (.298) 1.406 (.350) 1.264 (.114) MT1 Pre Post 2.050 (1.692) 1.976 (2.30) 1.620 (.749) 1.275 (.512) MT2 Pre Post 1.913 (.837) 1.666 (.885) 2.838 (2.552) 2.139 (1.828) TPV Pre Post .446 (.190) .368 (.618) .431 (.153) .403 (.153) PV Pre Post .432 (.151) .497 (.284) .1.146 (1.389) .887 (.258) Accel Pre Post .332 (.213) .317 (.147) .314 (.112) .374 (.153)

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42 Table 3-2. Summary ANOVA model for the pr imary dependent variable. Significant pvalue = 0..05 Dependent variable after two weeks of intervention Source Mean Square F (1,13) p-value HPT Time .426 8.132 .014 Task 5.197 1.700 .215 Time*Task 9.072 .901 .360 Table 3-3. Summary of ANOVA m odel the secondary dependent variables. Significant pvalue = 0.01. Dependent variables after two weeks of intervention Source Mean Square F (1,13) p-value MT 1 Time 4.48 2.248 .158 Task .614 .726 .410 Time*Task .260 .280 .606 MT 2 Time 6.84 1.897 .192 Task 3.14 8.167 .013 Time*Task .714 1.076 .319 TPV Time 1.491 .126 .728 Task 4.022 3.439 .086 Time*Task 1.143 .659 .427 PV Time 4.274 8.205 .013 Task .130 .212 .653 Time*Task .767 .767 .397 Accel Time 5.207 .392 .542 Task 6.864 1.114 .311 Time*Task 1.931 1.590 .229

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43 Table 3-4. Summary ANOVA model for posteri ori analysis of velocity profiles. Significant p-value = 0.01. Source Mean Square F (1,13) p value Jerk Time 1481.091 2.829 .116 Metric Task 659.802 1.033 .328 Time*Task 415.415 .333 .574 Speed Time 2.5885 2.888 .113 Metric Task 1.355 3.663 .078 Time*Task 8.377 .595 .454 MAPR Time 1.779 .007 .936 Task 1.525 .477 .502 Time*Task 2.500 .396 .540 Peaks Time 4.767 16.476 .001 Metric Task 4.939 .470 .505 Time*Task 1.796 .376 .550 Tent Time 4.408 1.053 .324 Metric Task 1.475 .093 .765 Time*Task 4.378 2.021 .179

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44 Table 3-5. Summary of individual change at posttest greater than the pre-test sd for each dependent variable (x > sd) Subjects FM-UE MT1 MT2 TMT TPV PV HPT Accel Pre/post 1 Task #1 Task #2 24/28 X X X X 2 Task #1 Task #2 51/49 X X X X X X X 3 Task #1 Task #2 48/44 4 Task #1 Task #2 33/38 X 5 Task #1 Task #2 51/53 6 Task #1 Task #2 46/45 X X X X 7 Task #1 Task #2 37/38 X X X 8 Task #1 Task #2 59/62 X 9 Task #1 Task #2 64/59 10 Task #1 Task #2 52/61 X X X 11 Task #1 Task #2 43/45 X X X 12 Task #1 Task #2 35/34 X X X X 13 Task #1 Task #2 18/23 X X 14 Task #1 Task #2 33/35 X % Change Task 1 Task 2 2/14 (14%) 2/14 (14%) 1/14 (7%) 1/14 (7%) 1/14 (7%) 2/14 (14%) 5/14 (36%) 5/14 (36%) 3/14 (21%) 2/14 (14%) 2/14 (14%) 0/14 (0%) 2/14 (14%) 4/14(29%)

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45 Hand Path Trajectory 1.453 1.392 1.000 1.100 1.200 1.300 1.400 1.500 1.600 1 HPT pre-testHPT post-test Figure 3-1. Significant main effect displayed for HPT for post-test. A value of 1 equals a straight line.

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46 Movement Time 2 1.789 2.489 0.000 0.500 1.000 1.500 2.000 2.500 3.000 3.500 1SecondsMT2 novel task #1 MT2 novel task #2 Figure 3-2. Significant main effect displayed for MT2 novel task #1.

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47 Peak Velocity 0.562 0.669 0.000 0.100 0.200 0.300 0.400 0.500 0.600 0.700 0.800 1Meters/SecondPV pre-test PV post-test Figure 3-3. Significant main effect displayed for PV on the post-test.

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48 Peaks Metric-0.761 -0.702 -0.82 -0.77 -0.72 -0.67 -0.62 -0.57 -0.52 -0.47 -0.42 -0.37 -0.32 -0.27 -0.22 -0.17 -0.12 -0.07 -0.02 pre-test post-test Figure 3-4. Significant main ef fect displayed for posterior i Peaks Metric post-test.

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49 CHAPTER 4 DISCUSSION Generalization is the ability to perfor m similar motor skills that were not specifically practiced as part of the training interv ention. Generalization is directly related to the amount of practice on a particular task and how mu ch motor learning occurred during the acquisition phase of the new the tas k. In addition, for ne urologically intact individuals learning sp ecific motor patterns, generali zation occurs only under highly similar spatial conditions that have simila r neural processing elements and demands.1-3 We do not know if this is also true for the basic coordination skills that persons relearn after stroke. Persons post-stroke are just re gaining the capacity to move and learning how to perform tasks with a decreased CMN pool output often their movements are influenced by pathological synergies. Th e critical components of invari ant task features necessary for generalization of a motor skill in indivi duals with stroke under these conditions have not been clearly delineated in the literature. 1 The specific aim of this study was to test spatial generalizat ion of repetitive rhythmic bilateral training to two novel reach ing tasks in individuals with stroke. The training task was a set of repetitive con tinuous movement reversals constrained by the BATRAC equipment which allowed only reachi ng forward in front of the body within a limited range (80% of the available reach). Th e transfer task (novel task #1) had similar neural demands for joint angles, workspace, visual gaze angles, and muscle timing compared to the training task but was not performed on the BATRAC. The second transfer task (novel task #2) had dissimila r joint angles, workspace, and visual gaze

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50 angles to the training task. It was predicted that improvement s in kinematic parameters of movement gained through tw o weeks of intervention woul d generalize to the similar novel task #1 at post-test but not to the di ssimilar novel task #2. Ge neralization occurred at post-test for HPT but surprisingly was e quivalent across the similar and dissimilar tasks.. Generalization of training was furthe r supported posteriori by the Peaks Metric that was also significant at post-interventi on. The changes in depe ndent variables taken together indicate improved c oordination with decreased st ops and starts in the novel reaching tasks. We also predicted that movement speed mi ght also improve with training. In fact, peak velocity was also significant at post-test with similar changes noted for both testing tasks. Perhaps, novel task #1 and novel task #2 did not present task features that were dissimilar enough to delineate a change between them kinematically post-intervention The remaining temporal dependent variab les of MT1, MT2, TPV, and acceleration did not generalize to either ta sk. The lack of change in these particular temporal parameters may have been because speed of movement was not emphasized in the training or testing tasks. On the other hand, the higher PV s uggests that for at least some of the reach, movements were faster. Perhap s subjects moved faster during parts of the reach, but slowed their moveme nts in the remaining sections of the reach, resulting an overall unchanged movement time. Only a more detailed analysis of the reaching strategy would allow firm conclusion on this issue. T hus, the results of this study offer only weak evidence that repetitive rhythmic bilateral tr aining may generalize to untrained tasks. Unfortunately there was no measure of actual intervention task learning in this study to delineate the lack of motor learning from th e lack of generalizati on. Instrumentation of

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51 the BATRAC equipment would allow for measurement of th e temporal coordination of the UEs providing more accurate measures of motor learning on the training task. This information could then be utilized to make further assumptions about motor learning of the intervention task compared to gene ralization of the novel transfer task. Neuroscience Rationale for Repetiti ve Rhythmic Bilateral Training The rationale for the potential of the BATR AC as an UE training tool post-stroke has been theorized to tap into basic ne urophysiological mechanisms that stimulate coordinative structures priming the nervous system and firing up the CMN pool. Studies have shown activation of both hemispheres w ith bilateral movements that are organizing in a tight phasic relationship.4-8The symmetrical temporal relationship between the hemispheres during bilateral activities may a ssist in laying down a template for basic movement components necessary for reaching. However, neither the specific movement characteristics of bilateral practice necessary for generalization nor th e level of severity of individuals post-stroke that would be most responsive to this type of therapy have been determined.9 The inconclusive findings of this present study are in contrast with the preliminary data regarding bilateral utiliza tion presented in the literature.10, 11 Using the BATRAC, Whitall et al.,10 demonstrated significant improvement in UE motor performance on the FM and WMFT. The results in the Whitall et al.10 study could be interpreted as generalization to untrained tasks since the items on these testing measures were not trained specifically in th e bilateral intervention. Luft et al.11 showed that repetitive rhythmic bilateral training using the BATRAC influences neural mechanisms underlying motor skill in a small number of subjects. They found increased hemispheric activation duri ng paretic arm movements after training.

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52 Although the motor skill assessed by fMRI in this study was not a reaching task as was the transfer task in the present study, increase d activity of the contra lesional hemisphere was observed. The Luft et al.11 study suggests that the BA TRAC intervention induces reorganization of motor networks in persons post stroke and Whitalls10 work further suggests that reaching post bilate ral intervention may improve. Differences in our subject population and the kinematic parameters selected as dependent variables could account for the differe nt results observed in this study. Whitall et al.10 used the FM and the WMFT to measur e efficacy of bilateral training. These assessments are a composite of summary scores over multiple items. Looking more closely at the items that make up the assessm ents reveals that some items increase and some items do not, while other items may even decrease a little. Therefore the overall score can show improvement, while individu al items themselves may not. This study focused on the kinematic measures of one single task only 2 tasks, one that was similar to the bilateral training. It is hard to compare the results of performance on only 2 tasks with summary scores on tests made up of many tasks. Perhaps had we chosen different tasks, we would have also found improvement across our subject sample. The task that was chosen demonstrated variability between subjects and overall did not show change across the multiple dependent variables, perhaps a different task or set of tasks may have. Ideally a combination of clinical, kinematic and kinetic measures would give a more complete understanding of movement behavior s. Therefore, it is difficult if not impossible to compare the results of the Whitall et al.10-12 studies with the present study due to the differences the nature of the outcome measures.

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53 Factors Potentially Affecting the Study Results Practice schedules are known to affect motor learning, and could possibly have played a role in our results.13, 14 This study utilized a distribu ted model of practice as did Whitall et al.10 Distributed practice allows for a rest period equal to or greater than the intervention period. In this study the interven tion period equaled 5 minutes and the rest period 10 minutes. Studies by Lee and Genovese15 have demonstrated in healthy individuals that transfer pe rformance was increased for groups that had longer rest periods versus work periods. Other studies have also shown that dist ributed practice has a large positive effect on learning.16, 17 The intervention in this study was also delivered in a blocked manner (grouping like trials together) however, while blocke d practice improves acquisition of a task, random practice appears to be superior for tr ue learning: re tention and generalization of the skill when tested after the training period of an intervention.18-20 Although, Whitall et al.10 demonstrated improved upper extremity f unctional measures with this type of practice (distributed blocked practice) dur ing bilateral training on the BATRAC. The blocked practice schedule perhaps limited th e degree of motor learning that occurred during the intervention and ther efore, limited generalization to motor skills not practiced directly in the training. Intr oducing a distributed random practice schedule for the in/anti phase trials or randomly changing the metrono me frequency on trials may have enhanced the amount of motor learning and thus ge neralization following this intervention. Random practice schedules incr ease the degree of problem solving during execution of the task by introducing variabil ity in the practice and in turn enhance retention and generalization ultimately improvi ng the amount of motor learning.1

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54 Providing practice in a more condensed form at (2 weeks versus 6 weeks) may have contributed to the study results. Whitall et al10-12 provided the same training but distributed the practice over a longer peri od of time. Currently it is not known if condensed practice offers differential benefits compared with more distributed practice. Dettmers21 found that CIMT distributed over 3 w eeks with a shorter trial per day ( 3 hours/day) demonstrated improved UE function and quality of life in persons post-stroke. Page et al22 also showed improved motor skills w ith a modified form of CIMT provided in a distributed fashion. However, no study has directly tested a condensed version against a more distributed version of an id entical therapy to determine whether such practice distribution influences the amount of motor gains experienced in therapy. The difference in the distribution of pr actice between this study and Whitalls10 may prove to be a critical factor in the re sultant study outcomes and should be directly investigated in future research. The distributi on and dose of practice to effect a change in motor learning in individuals post-stroke is clearly not understood. Several additional aspects of this training may not have been optimal for motor learning. First, repetitive rhythmic bilateral training may not serve as a robust learning model since problem solving and the devel opment of a reference of correctness of movement are not inherently strong or em phasized in the training. The environmental constraints of the BATRAC (the track and ches t restraint) and repetitive nature of the practice may have resulted in low neural de mands and little problem solving. The training was performed on a track that guided th e spatial trajectory of the movements furthermore; sensory cueing was provided fr om a metronome, which was self-paced to a comfortable speed for the participant. This a uditory cueing set up a temporal template for

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55 the individuals to match guiding the temporal parameters of the movements. Each end point stop provided kinestheti c cueing assisting with the timing of the reversal and indicated the proper extent of movement. T hus, the environment provided specific spatial and temporal features with predictable c onsequences, minimizing demands for problem solving. (A) (B) Figure 4-1. BATRAC invari ant features, (A) in-pha se and (B) anti-phase. Introducing a margin for potential errors during the interventi on might allow for increased problem solving during task learning which would facilitate the development of the capability to produce more effective m ovements and the ability to assess ones own movement behaviors. Error correction builds m ovement strategies and a larger repertoire of available movements to accomplish a task. Schmidt 1 has suggested that these aspects of motor learning are necessary to retrieve information from long-term memory for executing a motor skill. Shadmehr23 would argue these compone nts are critical for the formation of an internal model that woul d represent the physical dynamics of the limb and the workspace environment (where the motor skill is performed in relationship to the body/trunk/ upper extremities). Errors experien ced in the training would influence the performance of the motor skil l in an untrained but simila r task, contributing to the performance of the generaliza tion task after intervention. 1

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56 One could argue that learning to coordina te the two upper extremities for in-phase and anti-phase movement patterns as well as matching the metronome beat was practice that afforded some degree of problem solvi ng with this interventi on. In fact, observing participants during intervention revealed th at indeed there was some difficulty in coordinating the two limbs to obtain and main tain the temporal phasing of the movement patterns as well as temporal matching with the metronome. However, temporal phasing and matching were often accomplished with manual guidance of the therapist which has been shown to improve performance during the task but not improve motor learning.1, 3 Thus, the degree of problem solving and de velopment of a reference of correctness during the intervention may not have been sufficient enough for motor learning and generalization to a novel untrained similar task. If this is true, it is not surprising that little generalization was found. Another potential factor aff ecting the results was that perhaps subjects were not very engaged in the learning task. The nature of repetitive rhythmic bilateral training on the BATRAC was similar to an exercise wi th multiple repetitions versus meaningful functional task practice. Practici ng real life tasks that are mo tivating to the individual has been shown to improve acquisition of a motor skill. Wu et al.24demonstrated better kinematic performance of reaching moveme nts to real objects when compared to movements without relevant objects in persons post-stroke. Nelson et al.25 studied the effects of an occupationally embedded exerci se on bilaterally assisted supination in persons post-stroke. Significant results we re found for the group receiving real life (meaningful) practice compared to rote exerci se of the same task. Because the BATRAC lacked meaningful practice, the intervention may have he ld little motivation for the

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57 participants. Perhaps the results of this in tervention would be strengthened if such bilateral, repetitive exercise were combined with functional task practice that provides motivation and meaning for the participants for real life skills improving their motor learning outcome. Generalization is bolstered when the inva riant features are similar between the training intervention and the novel transfer task. Invariant featur es of a motor task consist of the unique traits and rules that are particular to that task. The components chosen as critical in this study: similar neural dema nds, joint angles, workspace, angle of visual gaze, and muscle and joint synergies, may not have been similar enough for generalization to consistently occur across the selected kinematic outcome measures. Motor learning, generalization, a nd retention of a task are strengthened when the training is varied.1, 3The movement of the upper extremities on the BATRAC did not allow for diversified movement and ther efore there was little room for error detection and the development of a reference of correction. This intervention involved little to no interaction with the environment since the objects in the environment did not change from one attempt to the next. The subject he ld a handle or was strapped to the handle on the BATRAC, which offered some degree of weight bearing on the apparatus, and therefore training motions were closed chain movements. The indivi dual was assisted to the end point stops if they were unable to complete the task inde pendently. The trunk of the individual was blocked from forward flexion by a chest plate and proximal arm motion was encouraged to complete the task. The demands of the task were externally paced, predictive; the movement was fixed w ithin a particular range and repetitive in nature requiring minimal monitoring by the participant. Although most subjects

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58 attempted to stay in time with the metronome they were assisted with verbal cues and occasional manual assistance to coordinate their movements with the beat of the metronome. Novel transfer task #1 was chosen becau se it had many of the characteristics thought to be important for generalization to occur. The workspace, visual gaze angles to the target, and joint angles re quired during the test reaches we re identical to the training intervention utilizing si milar muscle and joint synergies to perform the task (novel task #2 was dissimilar in these parameters). Schmidt1 et al have demonstrated that these components are necessary for a motor skill to generalize to a novel untrained task.1 While the lack of generaliza tion may have been due to a lack of learning altogether, the similar transfer task had other featur es that were different from the intervention task, which possibly contributed to the limited generalization. The transfer task may have required diffe rent processing compared to the training task. Unlike the training intervention there was no track or chest restraint utilized in the generalization task. The transfer task was a discrete unilateral re aching movement made in free space with the affected upper extremity to the target and back to the start position. The only environmental sensory cues were vi sual in nature: the target and the start position. No auditory cueing was used other than a verbal cue to begin the movement. The transfer task required transport of the upper extremity through space against gravity to the target and back to th e start position. One could postula te that both transfer tasks required greater muscle force to move the limb against gravity then was needed in the training task although these da ta were not collected in this study. Certainly more variations in the movement pa ttern were available as there were an increased number of

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59 df at upper extremity joints as with the tr unk in order to control the transfer task. Controlling such increased df in the transfer task was quite different than during training with the BATRAC as an environmental co nstraint and the chest plate limiting trunk forward lean. Allowing diversif ied movement within the exec ution of the novel task may have increased the requirements for attentiona l demands, neural control, problem solving, and error correction which were not inherent in the interv ention. The transfer task required focused attention on th e target, control of the upper extremity through space, and proprioception (to avoid over or under reac hing) unlike the training on the BATRAC where movements were guided by the track a nd kinesthic cues were provided by the distal stops. Summary Examination of the invariant features re veals differences in the interventiontraining task and the transfer task that may help to account for the lack of generalization across the dependent variables. Moving the arm fully through space required controlling many df which was clearly not something that was trained. Although some of the environmental constraints were similar: worksp ace, visual gaze angles; the change from a closed chain movement in the training in tervention to an open chain movement and increased movement possibilities on the tran sfer task introduced an increased demand on the muscular and neural systems as well as th e need to problem solve the execution of the task against gravity. Identifying the specific features of the repetitive rhythmic bilateral intervention that will foster generalization to an untrained moto r skill in stroke has yet to be determined. The training may not have provided a strong enough training stimulus or the components chosen as critical in this study: similar neur al demands, joint angles, workspace, angle of

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60 visual gaze, muscle and joint synergies may not have been similar enough for generalization to consistently occur across the selected ki nematic outcome measures. A lack of complexity in this intervention in regard to decreased demands to problem solve and lack of development of a reference of correctness may have influenced the amount of motor learning and further restricted genera lization of the intervention to a similar reaching task. Limitations to the Study This study was composed of a heteroge neous group of subjects therefore the statistical power was influenced by the vari ance between the subjects (Tables 3-2 and 3-3). A small sample size (n=14) makes it difficult to draw conclusions about the population in the study and results in a substa ntial reduction in power. Multiple analyses on dependent variables were performed but adjusted with a Bonferroni correction resulting in a more conservative alpha va lue further reducing the power. Previous bilateral studies have used small sample si zes and demonstrated si gnificant results on motor outcome measures but kinematic outc omes have not been reported. Calculating power at .80 for subsequent studies of this type of bilateral training with the same dependent variables would require 1050 subjec ts for significant resu lts. To counter the violations to the assumption of normality a larger sample size and homogenous sample would be beneficial in s ubsequent studies. A homogenous sample in the stroke population may be difficult to achieve due to the variability of the insult to the CNS. The inclusion criteria for this study were broad including subj ects that had only palpable extrinsic forearm finger muscle ac tivity and some active shoulder and elbow motion. Although this intervention was focuse d on proximal joint and muscle effector systems and did not train grasp, perhaps the crit eria should be modified to include some

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61 degree of finger and hand motion indicati ng more motor recruitment in the upper extremity. The inclusion criteria also did not include the ability to move the UE against gravity a specified degree, which was an inhere nt part of the transfer tasks and may have affected the amount of generaliz ation measured at posttest. Future Studies Some individuals may have improved w ith the intervention however delineating the variables that would discriminate those who might improve from those who might not improve were limited. Measures to asse ss multiple factors that potentially could influence each subjects baseline and post-test ing should be considered : 1) strength in the upper extremity, 2) coordinative patterns /m uscle joint synergies during movement 3) spasticity, 4) praxis 5) ex ecutive functioning, 6) motor lear ning style (spatial/temporal), and 7) sensory/proprioceptive st atus of the affected limb. Colle cting the above data of the participants capability would fu rther help to assess which subjects were able to benefit the most from this therapy. Although the side of the lesion was not used as exclusionary criteria in this study, it has b een documented that individuals with a left-sided lesion have more difficulty with rhythm keeping. 26-29 However, McCombe Waller and Whitall12demonstrated that persons post-stroke with left-sided lesions improved greater than persons with right-sided lesions duri ng intervention with th e BATRAC. Use of a metronome in the intervention training sessi ons may affect the results for particular subjects by cueing a temporal pace or disadva ntageous by creating in terference during the acquisition period of learning wh ere abstract neural signals are transformed into longterm memory for retrieval at a later time for execution.1, 23 In our study, nine subjects had left-sided lesions and five had right-sided lesions (Table 2-1). Although no clear pattern of interference or advantage was evident fr om the individual data this should be a

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62 consideration in future studies. Assessing th e issue of interference of the metronome or other rhythm keeper used in interventions during the acquisition stage of learning may be advantageous and revealing when evaluating the results. Models of the relationship of the dependent variables to each ot her are not clearly developed in the field of movement scienc e for the typical population and are evolving for the stroke population. The numbers of po ssible kinematic variab les and lack of a model make it difficult to pick just one or two that are expected to change or which would be the most important for function. The reliability and va lidity of kinematic measures in the stroke population has not been established and theref ore the stability of the measures has not been substantiated.30 There was no obvious pattern among individuals in regard to seve rity of involvement that pr edicted which subjects would improve and on what kinematic outcomes in this study. Several investigators have theorized that smoothness of the velocity pr ofile demonstrates im proved coordination of the reaching movement with a decrease in stops and starts in the pa ttern of reaching in healthy individuals a nd persons post-stroke.31-34 This supposition would connect the kinematic variables of PV, HPT, and sm oothness metrics, all contributing to the understanding of coordination and quality of reaching ability in persons post-stroke.30, 3537 Investigation into the correlation among these kinema tic variables related to performance on reaching tasks might allow selection of the most sensitive measures and the prediction in their change after intervention. Conclusions This study specifically tested generalization of repetitive rhythmic bilateral training to a similar novel task rather than the overall efficacy or motor learning in upper extremity function. The kinematic results sugges t that at a basic level repetitive rhythmic

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63 bilateral training in and of itself are not enough to effect a change in motor control, specifically generalization to an untrained novel motor skill across multiple dependent variables. The novel task may not have held enough of the invari ant features of the training task to truly test generalization of this intervention. The importance of task analysis of the invariant task features defined for the interven tion versus the transfer task cannot be underestimated. Identification of the critical components of the invariant features necessary for generalization in the stroke population has yet to be determined. The adequacy of the intervention in pr oviding an opportunity for motor learning involving problem solving and the development of a reference of correction without the connection of real life practice should be sc rutinized further. Las tly, the distribution of practice on a continuous task may affect mo tor learning and the resultant outcomes and should be investigated to determine optimal dosage during interventions post-stroke.

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64 LIST OF REFERENCES 1. American Heart Association. Know th e facts/Get the Stats. Available at: http://www.americanheart.org (Last accessed, April 2006) 2. Mayo NE, Wood-Dauphinee S, Ahmed S, Gordon C, Higgins J, McEwen S, Salbach N. Disablement following stroke. Disability and Rehabilitation. May-Jun 1999;21(5-6):258-268. 3. Nakayama H, Jorgensen HS, Raaschou HO, Olsen TS. Recovery of upper extremity function in stroke pati ents: the Copenhagen Stroke Study. Archives of Physical Medicine Rehabilitation. Apr 1994;75(4):394-398. 4. Duncan P, Studenski S, Richards L, Goll ub S, Lai SM, Reker D, Perera S, Yates J, Koch V, Rigler S, Johnson D. Randomized c linical trial of ther apeutic exercise in subacute stroke. Stroke. Sep 2003;34(9):2173-2180. 5. Chen R, Cohen LG, Hallett M. Nervous system reorganization following injury. Neuroscience. 2002;111(4):761-773. 6. Hallett M. Plasticity of the human mo tor cortex and recovery from stroke. Brain Res Brain Res Rev. Oct 2001;36(2-3):169-174. 7. Shumway-Cook A, Woollacott MH. Motor control : theory and practical applications 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001. 8. Kandel ER, Schwartz JH, Jessell TM. Principles of neural science 4th ed. New York McGraw-Hill, Health Professions Division, c2000.; 2000. 9. Schimidt R, Lee TD. Motor control and learni ng: a behavioral emphasis 4th ed. Champaign, IL: Human Kinetics; 2005. 10. Kelso JA. Phase transitions and critical behavior in human bimanual coordination. Am J Physiol. Jun 1984;246(6 Pt 2):R1000-1004. 11. Kelso JA. On the oscill atory basis of movement. Bulletin of the Psychonomic Society. 1981;18:63. 12. Tanji J, Okano K, Sato KC. Neuronal ac tivity in cortical motor areas related to ipsilateral, contralatera l, and bilateral digit movements of the monkey. Journal of Neurophysiology. Jul 1988;60(1):325-343.

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65 13. Debaere F, Wenderoth N, Sunaert S, Va n Hecke P, Swinnen SP. Changes in brain activation during the acquisition of a new bimanual coodination task. Neuropsychologia. 2004;42(7):855-867. 14. Debaere F, Wenderoth N, Sunaert S, Va n Hecke P, Swinnen SP. Cerebellar and premotor function in bimanual coordinati on: parametric neural responses to spatiotemporal complexity and cycling frequency. Neuroimage. Apr 2004;21(4):1416-1427. 15. Gerloff C, Andres FG. Bimanual coordi nation and interhemis pheric interaction. Acta Psychology (Amst). Jun 2002;110(2-3):161-186. 16. Stinear JW, Byblow WD. Rhythmic bilateral movement training modulates corticomotor excitability and enhances upper limb motricity poststroke: a pilot study. J Clin Neurophysiol. Mar-Apr 2004;21(2):124-131. 17. Byblow WD, Lewis G, Stinear J, Carson RG. The modulation of excitability in corticospinal pathways during rhythmic m ovement. In: Swinnen SP, Duysens, eds. Neuro-behavioral determinants of inte rlimb coordination A multidisciplinary approach Boston: Kluwer Acdemic publishers; 2004:155-185. 18. Luft AR, McCombe-Waller S, Whitall J, Forrester LW, Macko R, Sorkin JD, Schulz JB, Goldberg AP, Hanley DF. Repe titive bilateral arm training and motor cortex activation in ch ronic stroke: a randomi zed controlled trial. Jama. Oct 20 2004;292(15):1853-1861. 19. Wyller TB, Sveen U, Sodring KM, Pettersen AM, Bautz-Holter E. Subjective wellbeing one year after stroke. Clinical Rehabilitation. May 1997;11(2):139-145. 20. Umphred D. Merging neurophysiologic a pproaches with contemporary theories: setting the stage for disc ussion. In: Lister MJ, ed. Contemporary management of motor control problems: proceedings of the II STEP conference Alexandria, Va: Foundation for Physical Therapy; 1991:127-140. 21. Bobath B. Treatment of adult hemiplegia. Physiotherapy. Oct 1977;63(10):310313. 22. Brunnstrom S. Movement therapy in hemiplegia ; a neurophysiological approach Philadelphia, PA: Harper and Row; 1970. 23. Adler S, Beckers D, Buck M. PNF in practice: an illustrated guide 2nd ed. New York: Springer; 2000. 24. Davies P, M. Steps to follow: the comprehensive treatment of patients with hemiplegia 2nd ed: Springer; 2000. 25. Singer R. Motor learning and human performance 3rd ed. New York: Macmillan; 1980.

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69 62. Mudie MH, Matyas TA. Can simultane ous bilateral movement involve the undamaged hemisphere in reconstruction of neural networks damaged by stroke? Disability and Rehabilitation. Jan 10-20 2000;22(1-2):23-37. 63. Whitall J, McCombe Waller S, Silver KH, Macko RF. Repetitive bilateral arm training with rhythmic auditory cuei ng improves motor function in chronic hemiparetic stroke. Stroke. Oct 2000;31(10):2390-2395. 64. Platz T, Bock S, Prass K. Reduced skilfulness of arm motor behaviour among motor stroke patients with good clinical recovery: does it indicate reduced automaticity? Can it be improved by unilatera l or bilateral training? A kinematic motion analysis study. Neuropsychologia. 2001;39(7):687-698. 65. Stinear JW, Byblow WD. Di sinhibition in the human moto r cortex is enhanced by synchronous upper limb movements. Journal of Physiology. Aug 15 2002;543(Pt 1):307-316. 66. Kelso JA, Holt KG, Ruben P, Kugler P. Patterns of human interlimb coordination emerge form the properties of non-linear limit cycle oscillatory proceses: theory and data. Journal of Motor Behavior. 1981;13:226-261. 67. Criscimagna-Hemminger SE, Donchin O, Gazzaniga MS, Shadmehr R. Learned dynamics of reaching movements generali ze from dominant to nondominant arm. J Neurophysiol. Jan 2003;89(1):168-176. 68. Werhahn KJ, Conforto AB, Kadom N, Ha llett M, Cohen LG. Contribution of the ipsilateral motor cortex to recovery after chronic stroke. Ann Neurol. Oct 2003;54(4):464-472. 69. Temprado JJ, Swinnen SP. Dynamics of l earning and transfer of muscular and spatial relative phase in bimanual coordi nation: evidence for ab stract directional codes. Exp Brain Res. Jan 2005;160(2):180-188. 70. Welsh TN, Almeida QJ, Lee TD. The eff ect of postural stability and spatial orientation of the upper limbs on interlimb coordination. Exp Brain Res. Mar 2005;161(3):265-275. 71. Sainburg RL, Wang J. Interlimb transfer of visuomotor rotations: independence of direction and final position information. Exp Brain Res. Aug 2002;145(4):437-447. 72. Sunderland A, Tinson DJ, Bradley EL, Fl etcher D, Langton Hewer R, Wade DT. Enhanced physical therapy improves rec overy of arm functio n after stroke. A randomised controlled trial. Journal of Neurology, Ne urosurgery, and Psychiatry. Jul 1992;55(7):530-535.

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70 73. Sterr A, Elbert T, Berthold I, Kolbel S, Rockstroh B, Taub E. Longer versus shorter daily constraint-induced movement therapy of chronic hemiparesi s: an exploratory study. Archives of Physical Medicine and Rehabilitation. Oct 2002;83(10):13741377. 74. Ouellette MM, LeBrasseur NK, Bean JF, Phillips E, Stein J, Frontera WR, Fielding RA. High-intensity resistance training im proves muscle strength, self-reported function, and disability in l ong-term stroke survivors. Stroke. Apr 22 2004;35:1404-1409. 75. McCrea PH, Eng JJ, Hodgson AJ. Biomechanic s of reaching: clinical implications for individuals with acquired brain injury. Disabil Rehabil. Jul 10 2002;24(10):534541. 76. Cunningham CL, Stoykov ME, Walter CB. Bilate ral facilitation of motor control in chronic hemiplegia. Acta Psychol (Amst). Jun 2002;110(2-3):321-337. 77. Cirstea MC, Levin MF. Compensatory strategies for reaching in stroke. Brain. May 2000;123( Pt 5):940-953. 78. Cirstea MC, Mitnitski AB, Feldman AG, Levin MF. Interjoint coordination dynamics during reaching in stroke. Experimental Brain Research. Aug 2003;151(3):289-300. 79. Rohrer B, Fasoli S, Krebs HI, Hughes R, Volpe B, Frontera WR, Stein J, Hogan N. Movement smoothness changes during stroke recovery. J Neurosci. Sep 15 2002;22(18):8297-8304. 80. McCombe Waller S, Whitall J. Hand do minance and side of stroke affect rehabilitation in chronic stroke. Clin Rehabil. Aug 2005;19(5):544-551. 81. Shea CH, Kohl RM. Specificity and variability of practice. Res Q Exerc Sport. Jun 1990;61(2):169-177. 82. Shea CH, Kohl RM. Composition of practic e: influence on the retention of motor skills. Res Q Exerc Sport. Jun 1991;62(2):187-195. 83. Lee TD, Genovese ED. Distribution of prac tice in motor skill acquisition: different effects for discrete and continuous tasks. Res Q Exerc Sport. Mar 1989;60(1):5965. 84. Ammons R. Acquisition of motor skill: III. Effects of initiallly distributed practice on rotary pursuit performance. Psychology. 1950;40:777-787. 85. Reynolds B, Bilodeau I. Acquisition and re tention of three psychomotor tests as a function of distribution of practice during acquisition. Journal of Experimental Psychology. 1952;44:19-26.

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71 86. Tsutsui S, Lee TD, Hodges N. Contextual interference in learning new patterns of bimanual coordination. Journal of Motor Behavior. 1998;30:151-157. 87. Newell KM, McDonald P. Practice: A serach for task solutions. American Academy of Physical Education, Enhancing human pe rformance in sport: New concepts and developments. Vol 25. Champaign, IL: Human Kinetics; 1992:51-59. 88. Shadmehr R. Generalization as a behavior al window to the neural mechanisms of learning internal models. Hum Mov Sci. Nov 2004;23(5):543-568. 89. Wu C, Trombly CA, Lin K, Tickle-Degnen L. A kinematic study of contextual effects on reaching performance in persons with and without stroke: influences of object availability. Arch Phys Med Rehabil. Jan 2000;81(1):95-101. 90. Nelson DL, Konosky K, Fleharty K, Webb R, Newer K, Hazboun VP, Fontane C, Licht BC. The effects of an occupationally embedded exercise on bilaterally assisted supination in persons with hemiplegia. Am J Occup Ther. Sep 1996;50(8):639-646. 91. Alcock KJ, Wade D, Anslow P, Passingha m RE. Pitch and timing abilities in adult left-hemisphere-dysphasic and right-hemisphere-damaged subjects. Brain Lang. Oct 15 2000;75(1):47-65. 92. Mavlov L. Amusia due to rhythm agnosia in a musician with left hemisphere damage: a non-auditory supramodal defect. Cortex. Aug 1980;16(2):331-338. 93. Murayama J, Kashiwagi T, Kashiwagi A, Mimura M. Impaired pitch production and preserved rhythm produc tion in a right brain-dama ged patient with amusia. Brain Cogn. Oct 2004;56(1):36-42. 94. Vignolo LA. Music agnosia and auditory a gnosia. Dissociations in stroke patients. Ann N Y Acad Sci. Nov 2003;999:50-57. 95. Krebs HI, Hogan N, Aisen ML, Volp e BT. Robot-aided neurorehabilitation. IEEE Trans Rehabil Eng. Mar 1998;6(1):75-87. 96. Platz T, Denzler P, Kaden B, Maurit z KH. Motor learning after recovery from hemiparesis. Neuropsychologia. Oct 1994;32(10):1209-1223. 97. Trombly CA, Wu CY. Effect of rehabil itation tasks on organi zation of movement after stroke. Am J Occup Ther. Jul-Aug 1999;53(4):333-344.

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72 BIOGRAPHICAL SKETCH Claudia Ann Rutter Senesac, PT, MHS, PCS, has over 27 years of pediatric clinical experience. She is the owner and administra tor of a pediatric phys ical therapy private practice since 1984 and is a board certified clinic al specialist in pedi atrics. She received her bachelors degree in physical therapy and masters degree in health science from the University of Florida. She is graduating w ith a Doctor of Philosophy in rehabilitation science with her resear ch interest focused on motor learning and motor control in neurological and neuromuscular impaired populations: adult i ndividuals who have suffered a stroke, pediatric individuals that have suffered a SCI, cerebral palsy and neuromuscular diseases. Inve stigations have included c onstraint induced movement therapy, upper extremity intervention protocol s for recovery, and locomotor training in the pediatric population. She has been an adjunc t faculty member of the Physical Therapy Department at the University of Florida since 1979 and faculty Lecturer since 2003. Her primary teaching responsibilitie s in the entry-level doctorate program include Functional Anatomy I and II and Pediatrics in Physical Therapy.


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Full Text












GENERALIZATION OF REPETITIVE RHYTHMIC
BILATERAL TRAINING

















By

CLAUDIA ANN RUTTER SENESAC


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


2006

































Copyright 2006

by

Claudia Ann Rutter Senesac

































This document is dedicated Emily Salles Senesac, Robert Edward Senesac and in
Memory of Ashley O'Mara Senesac and Robert Basil Rutter















ACKNOWLEDGMENTS

I thank my family for their patience and understanding as I pursued a dream to

learn more about the body and mind. With their love and encouragement I complete this

journey and begin another.
















TABLE OF CONTENTS

page

A C K N O W L E D G M E N T S ................................................................................................. iv

LIST OF TA BLES ........ .......................... ........ ...... ................ ............ vii

LIST OF FIGURES ..................... .......... ................. ................. viii

LIST OF OBJECTS ......... ........................... .......... .......... ........... ix

A B ST R A C T ................. .......................................................................................... x

CHAPTER

1 IN TR OD U CTION ............................................... .. ......................... ..

Stroke and UE Rehabilitation ............. .... ........ ...... ...............
Theoretical Basis .......................... .............. .... ..... 5
Neuroplasticity and Use-dependent Plasticity ............................................................6
M otor L earning ...................... ............... ............. ... .............................. . 9
B ilateral Training................................................... 14
B iom echanics of R teaching ................................................................ ............... ..... 18
S u m m a ry .......................................................................................................1 9
S p ecific A im s ...............................................................2 1
Research Aim s and Hypotheses ........................................ ....... ............... 22
G e n e ra l a im 1 ......................................................................................... 2 2
Specific aim la and lb ...................................... ............................22
Primary hypotheses la and lb for spatial parameter............................. 22
Secondary hypotheses 2a and 2b for temporal parameters ........................23

2 M E T H O D S ......................................................... ................ 2 5

Experim mental D design .......................................... .. .. .... ........ .. ....... 25
S u b j e c ts .......................................................................................2 5
P ro c e d u re .......................................................................................................2 6
O utcom e M measures .............................................................................................. 29
Kinematic analysis of reaching ........................................29
N ovel Task #1(Sim ilar) ........................................ ................................30
N ovel Task #2(D issim ilar) ............................................................................ 31
Primary Spatial Dependent Variable.............. ...................................32


v









Secondary Temporal Dependent Variables ........................................................32
Posteriori of velocity profiles ............ ..................... ..................... 33
D ata A n aly sis ............................. ....................................................... ............... 3 4

3 R E S U L T S .............................................................................3 6

Data Analysis................................ .............. 36
Primary Spatial Dependent Variable..................................... ............... 36
H and path trajectory ..................... .. ..... ........... .. ...... .................... ..37
Secondary Temporal Dependent Variables ............. ....................................37
M ovem ent tim e .......................... .... .............. ................ ...........37
Time to peak velocity .............. ..... ........ ................... 38
P e a k v e lo c ity ................................................................................................. 3 8
A c c e le ra tio n ........................................................................................... 3 9
Posteriori of velocity profiles .. ........................... .....................39
D descriptive Individual D ata........................................ .................... ............... 39

4 DISCUSSION .................. .. .............. ..................49

Neuroscience Rationale for Repetitive Rhythmic Bilateral Training......................51
Factors Potentially Affecting the Study Results................................. ... ................ 53
Sum m ary ................ .......... ...... ... ....................................... 59
L im stations to the Study .......... .... .......................... ............. ....60
F utu re Stu dies ....................................................... 6 1
C o n c lu sio n s........................................................................................................... 6 2

LIST OF REFEREN CE S ........................................ ........................... ............... 64

BIOGRAPH ICAL SKETCH ...................................................... 72
















LIST OF TABLES


Table p

2-1 D em graphic data ...................... ...................... ................... .. ...... 27

3-1 Means and standard deviations (sd) for all dependent variables ...........................41

3-2 Summary ANOVA model for the primary dependent variable ............................42

3-3 Summary of ANOVA model the secondary dependent variables............................42

3-4 Summary ANOVA model for posteriori analysis of velocity profiles...................43

3-5 Sum m ary of individual change ........................................ ......................... 44
















LIST OF FIGURES


Figure pge

2-1 Illustration of testing conditions for similar spatial orientation novel task #1.........30

2-2 Illustration of testing conditions for dissimilar spatial orientation novel task #2 ....31

3-1 Significant main effect displayed for HPT for post-test.........................45

3-2 Significant main effect displayed for MT2 novel task #1................................ 46

3-3 Significant main effect displayed for PV on the post-test................... ............47

3-4 Significant main effect displayed for posteriori Peaks Metric...............................48

4-1 BATRA C invariant features ............... .................... .................... .. ........... 55
















LIST OF OBJECTS

Object page

2-1 B A TR A C Inphase. ............................................. ................... .. .....29

2-2 B A T R A C A ntiphase ....................................................................... ..................29

3-2 Testing conditions for generalization Pre-test..................................................40

3-3 Testing conditions for generalization Post-test ............................................ 40















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

GENERALIZATION OF REPETITIVE RHYTHMIC BILATERAL TRAINING

By

Claudia Ann Rutter Senesac

May 2006

Chair: Lorie Richards
Major Department: Rehabilitation Science

Background and purpose: Bilateral training (BT) is an alternative approach in

neurorehabilitation for individuals post stroke. Bilateral training activities may increase

the activity of the affected hemisphere and decrease the activity in the unaffected

hemisphere providing a balancing effect between hemispheric corticomotorneuron

excitability. One bilateral approach, repetitive rhythmic bilateral training, developed and

researched by Whitall, has shown improved motor function after intervention post stroke.

Yet, an important question is whether this type of practice will result in improvements in

untrained movements. The ability to perform related untrained motor tasks is

generalization. The purpose of this study is to determine if repetitive rhythmic bilateral

training will promote spatial generalization to a novel task.

Methods: Fourteen participants with hemiparesis completed the study. The

intervention used an arm training machine-BATRAC-consisting of two paddles mounted

in nearly frictionless tracks. The participants moved the handles back and forth in a

rhythmic manner for 5-minute blocks. Half of the blocks were in-phase; the other half of









the blocks were anti-phase. Practice sessions were 4 days/week, 2:25 hours/day, for 2

weeks, for a total of 18 hours of training. We measured movement time, time to peak

velocity, hand path trajectory, peak velocity, and acceleration using the Vicon motion

analysis system during 2 reaches to target tasks pre- and post- training. Each participant

gave informed consent according to University of Florida Institutional Review Board and

North Florida/South Georgia Subcommittee for Clinical Investigation requirements prior

to participation.

Results: Improvements were found at post-test only for hand path trajectory and

peak velocity. They were equivalent across similar and dissimilar tasks. Movement time

2 was less for novel task #1 compared to novel task #2 but equivalent across pre- and

post- testing periods. No interaction effects were found.

Conclusion: Unlike Whitall, our kinematic results suggest that repetitive rhythmic

BT alone is not sufficient to change motor control, specifically generalization to similar,

but untrained tasks. However, the small and heterogeneous study sample precludes

definitive conclusions regarding the usefulness of this practice paradigm for promoting

motor skills post-stroke.














CHAPTER 1
INTRODUCTION

Stroke strikes 700,000 persons each year in the United States resulting in varying

degrees of permanent disablement.1 Many of the people affected by stroke will have a

residual upper extremity (UE) motor and sensory deficit that will influence their ability to

participate in life roles. These deficits typically involve decreased UE use and

coordinative control of the arm and hand for activities of daily living, gesturing, and

bilateral activities and will affect 78% of those individuals surviving stroke.2 Furthermore

the vast majority of those with severe UE paresis will not recover full function of their

arm and hand after 6-11 weeks of "traditional" therapy. 3 The effectiveness of current

rehabilitation approaches for restoration of UE function has not identified one

intervention as being superior to others in gaining function in the UE.3 4 Scientific

evidence now suggests that to enhance motor recovery post stroke, one of the critical

components in an intervention protocol is practice.5'6 Thus finding effective UE motor

rehabilitative interventions is an important goal.

Development of new, more effective rehabilitation techniques depends upon

understanding the neural, physical and behavioral expression of movement.7 Specifically,

an understanding of the CNS's ability to recover in the face of injury, and the extrinsic

factors that can influence that recovery, is essential for successful neurorehabilitation.

Key to motor recovery following stroke is the CNS' ability to learn or relearn motor

behaviors. This recovery can occur spontaneously, or more likely, will require practice

of the lost motor abilities to facilitate reorganization of the motor cortex.5'7'8









Re-training and practicing every motor behavior that the individual will be called

upon to use in everyday life is unrealistic. Motor control theory suggests that all

movement behaviors, or tasks, contain essential features that can be entrained with

practice.9 Motor learning theory further suggests that these features, once trained, can be

transferred to another task that requires the same features(s). This is called a

generalization effect.9Taking advantage of this effect could have a significant impact on

UE rehabilitation post-stroke.

Bilateral training is an emerging approach in neurorehabilitation for individuals

post-stroke. Bilateral movements form a tight phasic relationship organizing the behavior

to perform as a functional synergy.9-11 Animal and human research has supported the

notion that both hemispheres are active during bilateral activities. 1214 During the

acquisition phase of learning a bilateral skill, there is a functional coupling of motor areas

in both cerebral hemispheres.15 In persons post-stroke, bilateral activities have increased

activity of the damaged hemisphere and decreased activity in the undamaged to facilitate

a more balanced effect of between-hemisphere corticomotorneuron (CMN) excitability.16,

17 For example, repetitive bilateral arm training increased activation in the contralesional

cerebrum and ispsilesional cerebellum after 18 hours of training.18 The response of the

motor cortex to bilateral training with reorganization is encouraging. Bilateral training

may lay a foundation in individuals post stroke for engaging coordinative structures

allowing the execution of basic motions and movement even though the practice is not

real life task practice.

The basic motions provided in bilateral training may entrain both hemispheres and

provide the essential features necessary to generalize to similar tasks not specifically









trained in the intervention. Generalization of a task should be optimal when the neural

demands and conditions are similar.9 However, because functional tasks are not directly

trained, test of the generalization is important. The purpose of this study is to determine if

repetitive bilateral training will promote spatial generalization to a novel task.

The following literature review is composed of five main sections and will serve to

orient the reader to foundation principles underlying the purpose and hypotheses of this

project. The sections will include the following: 1) stroke and UE rehabilitation; 2)

theoretical basis; 3) neuroplasticity and use-dependent plasticity; 4) motor learning:

practice and generalization, and 5) bilateral training in stroke rehabilitation. First, the

traditional view of stroke and rehabilitation will be compared and contrasted with more

recent views based upon new scientific evidence. Second, conceptual frameworks for

studying UE recovery following stroke will be reviewed. In the third section, basic

elements of CNS neuroplasticity and training effects on CNS plasticity will be reviewed.

Motor learning principles including generalization, and practice and their relevance to

stroke rehabilitation will then be discussed in the fourth section. Finally, the use of

bilateral training incorporating key motor learning principles will be discussed as a

potential new therapeutic approach.

Stroke and UE Rehabilitation

Each year 700,000 persons will suffer a new or recurrent stroke in the United States

resulting in varying degrees of permanent disablement.19 Many of the people affected by

stroke will have a persistent upper extremity (UE) motor and sensory deficit that will

influence their ability to participate in activities of daily living and life roles. Motor and

sensory deficits typically involve decreased coordinative movement of the arm and hand

and UE use for activities encountered in a person's daily environment including self-help









skills, gesturing and bilateral activies.2 Furthermore, the vast majority of those with

severe UE paresis will not recover complete function of their arm and hand after 6-11

weeks of "traditional" therapy. 3 In fact, use of the UE is so important that subjective

measures of "well being" are directly related to perceived motor impairments of the arm

affecting quality of life. 19 Thus, developing effective UE motor rehabilitative

interventions is extraordinarily important, especially in light of current rehabilitative

approaches to UE treatment that lack clear consensus, and are conflicted and

unsubstantiated. 34

Upper extremity interventions in the stroke population have historically focused on

treatment of single limb movements; treating the intact and affected arm separately.2024

Methods designed to restore motor skill in the affected UE are influenced by facilitation

models of motor recovery and emphasize handling or guidance to achieve more normal

movement patterns. Practice under these conditions improves performance, but improved

performance of a task does not necessarily lead to relatively permanent changes, which

characterize motor learning.7' 9 Performance during motor skill learning is a temporary

change in behavior that is observed during practice sessions but may not be retrieved at a

later time for execution.9 This may be because practice under traditional motor

rehabilitative approaches allows for few errors, and little problem solving (by the learner)

of the criteria inherent in the task.25 In addition many of these traditional therapy

approaches were based on the hierarchical-reflex theory, which has not held up under the

scrutiny of the current motor control and motor learning literature. Nonetheless, these

facilitory models continue to be used as traditional standard of care for rehabilitation.26-29









Theoretical Basis

The hierarchical-reflex model suggests that motor learning in rehabilitation is a

stepwise sequence of motor recovery and motor development from lower levels to higher

levels of control.30 Treatment based on this theory of motor control often will focus on

the movements that are most automatic requiring sensory stimulation from the therapist,

progressing to more skilled voluntary tasks. This approach is often referred to as a

"traditional" approach utilizing facilitation from the therapist to accomplish goals. New

approaches to rehabilitation are beginning to surface based on the concepts of

neuroplasticity and motor learning theories.

Bernstein first proposed the systems theory in the early to mid 1900's although it

was not incorporated into rehabilitation until the early 1980's. 9,25, 31 Bernstein viewed

the nervous system as one of many contributors to movement execution but not the

controller of movement. Movements are seen as a result of an interaction among many

systems including internal and external environments, organized around behavioral goals

with distributed control.

Bernstein noted that there were many degrees of freedom (df) available to produce

a movement. Different df are characteristic of a task, environmental demands, and the

performer. These df need to be controlled for effective movement to be accomplished.

He purposed that the formation of synergies (groups of muscles and joints constrained

together) could control the multiple df problem. This model can describe how learning of

a new motor skill takes place. In the early stages of learning a new task the movement

may be simple. Movement at one joint may be allowed to vary with intermediate joints

held stiffly utilizing cocontraction of muscles to control the df. Once the movement is

learned muscle cocontraction is reduced and the movement becomes more fluid









indicating the ability of the central nervous system to use multiple resources to

accomplish a task. In stroke, these synergies are constrained in a pathological manner

with stereotypical movements observed with attempts to move.21' 22 Difficulty is noted in

the ability to control the multiple dfthat are available in the extremities and trunk. This

inability to form normal synergies of movement leads to compensation and decreased

fluidity of movement in persons post- stroke.24

Neuroplasticity and Use-dependent Plasticity

Brain infarction results in a semi-reversible set of pathophysiological events

including swelling of the affected area, impaired circulation and pyramidal cell injury or

death.8 Recovery from brain infarction involves plasticity-the ability of the central

nervous system to reorganize after brain injury. 32 Developing an understanding of the

post-ischemic plasticity and its effect on motor control and motor learning has become

the focus of current rehabilitative efforts.9 The CNS post-stroke begins a process of

spontaneous recovery which involves neurological reorganization. In contrast to

individuals with intact nervous systems, attempts to move after stroke result in decreased

activation in the affected motor cortex with increased activity in the non-affected

hemisphere.8 33 34 These findings suggest even though crossed motor pathways are

damaged, after stroke recruitment of preexisting uncrossed motor neural pathways may

be accessed.34 Ipsilateral motor unit activity can be induced when the ipsilateral dorsal

premotor cortex area is stimulated by TMS. This stimulation has demonstrated shorter

latencies when compared to contralateral stimulation of the premotor cortex when the

hand is moved in stroke patients.35 Even in individuals who have recovered from stroke,

there is an increased activation of the CMN pool in the undamaged hemisphere when

compared to persons with intact nervous systems performing a finger tapping









movement.33 36 However, recovery from stroke is associated with decreasing activation

in the contralesional hemisphere and increasing activation in the lesioned hemisphere; a

more normal balance of activation is seen.

Motor recovery post stroke is augmented by rehabilitation. Rehabilitation of

individuals post-stroke involves motor learning. Motor learning is characterized by a set

of processes that are associated with practice. These processes influence change in the

internal state of the central nervous system and become relatively permanent, capable of

being retrieved from long-term memory centers into working memory for motor

execution.5 7 9 In the case of the individual with stroke, rehabilitation is concerned with

the relearning of once familiar motor skills using new motor pathways. Coordinative

patterns of movement must be practiced to create these new motor pathways during

recovery for the execution of motor skills. The capability by which the brain modifies

structure and function in response to learning or brain damage is neuroplasticity.5 7

Several mechanisms of reorganization of cortical areas after stroke or brain injury

have been proposed. Unmasking is a term used to indicate decreased inhibition of pre-

existing excitatory synapses allowing for functionally inactive connections to become

active. Changes that are rapidly induced during spontaneous recovery after injury are

believed to be unmasking.5 Synaptogensis refers to growth of new neural connections and

is related to environment and practice.8 Long term potentiation (LTP) involves the

increasing sensitivity of synapses pre-synaptically through constant stimulation with a

resultant larger postsynaptic output. Long term potentiation and synaptogensis are

believed to occur over longer time periods, coming into play during intense practice.5

Sparing refers to the areas of the brain that were not damaged during the injury and may









be adjacent or interconnected to the damaged area. These areas of sparing have been

shown to play a role in reorganization of cortical maps.5' 37-39

Nudo et al. has demonstrated in a study with squirrel monkeys that the motor

cortical areas of the brain can reorganize after brain injury.32 Further investigation by this

group of researchers suggest that reorganization of cortical maps is dependent on

rehabilitation and practice.38 40-42 Use-dependent plasticity relies on activation of the

brain during periods of practice.57 Calautti and Baron reviewed neuroimaging studies of

individuals post-stroke and found reorganization of motor areas with enhanced activity in

existing neural networks. In this review, both motor training and pharmacological

interventions were found to induce this increased activity in the damaged hemisphere

associated with recovery of function and improved motor skills.43 Calautti and Baron

observed significant changes in neuromapping in individuals involved in intense practice

of specific tasks. For example, neuroplasticity associated with motor rehabilitation has

been documented with the treatment paradigm constraint-induced movement therapy

(CIMT).44-46 Cortical reorganization in motor output areas of the damaged hemisphere

and in areas adjacent to the damaged site have been demonstrated as a result of intense

practice.37 47 48 Jang et al. demonstrated cortical reorganization by fMRI after 4 weeks

(4 days/week, 40 minutes/day) of task oriented training (practicing of functional

tasks). This training consisted of six tasks to improve UE function in 4 individuals with

chronic stroke. Cortical reorganization was evident with changes in the activation of the

primary sensory motor cortex (decrease in activation of the unaffected hemisphere and

increase activation in the affected hemisphere).49 These studies indicate that practice is an









important component of the motor rehabilitative process as it facilitates neuroplasticity of

the cortical motor areas.

Motor Learning

Motor learning and the underlying neuroplastic changes are dependent on

practice. 5,7 In the face of neuropathology, persons post-stroke must confront

relearning skills that once were part of their daily routine. Determining the conditions for

optimal learning in persons post-stroke requires an understanding of the different types of

practice available during a rehabilitation program. The type of practice schedule that is

selected during therapy has a strong effect on the process of motor learning effecting the

basic components of movement and building the specifics of coordination for activities.9

Certain principles of motor learning are well established in healthy adults but not well

understood in stroke.

Mass practice builds capacity (skillfulness, ability) by utilizing longer practice

periods and short rest periods between trials. However, this type of practice can lead to

fatigue resulting in detrimental results for actual motor learning, transfer (generalization),

and retention.9 Practicing under conditions of fatigue may affect the synergies that are

engaged during the learning of the task, and ultimately the ability to retrieve the

appropriate information for the execution of the task at a later time (retention and

transfer) is reduced. Distributed practice provides shortened practice sessions and equal

or longer rest periods than the actual task trials. This type of practice improves

performance without the complication of fatigue and has demonstrated positive effects on

motor learning as measured by transfer trials. 9

The sequence of practice is also an essential component to motor learning. Practice

that repeats one task for a set number of trials before moving on to the next task is









referred to as blockedpractice. This type of practice has low contextual interference

(learning within the context of only one task) as the person learns the criteria for the task

and performs several repetitions in the acquisition phase before moving on to another

skill. Blocked practice enhances performance but may be detrimental to retention or

permanent learning as there is a low demand on problem solving once the criteria of the

skill are understood. Blocked practice is used in therapy when the task is just being

introduced and the participant is becoming familiar with the criteria of the movement.

Random practice intermixes trials so that no task is repeated on two consecutive trials.

The order of presentation of trials is varied presenting a high degree of contextual

interference (learning one task in the context of other tasks). Random practice provides

different patterns of coordination with different underlying motor programs with a range

of solutions for motor tasks.50 This type of practice can be detrimental to performance

during the acquisition phase but beneficial to motor learning and retention with the

continual demand on retrieving the criteria of the task.51' 52

During rehabilitation, therapists attempt to help the individual with stroke build the

ability to produce coordinative movements. Because it is impossible during rehabilitation

to practice every motor task the person will encounter in daily activity, it is believed that

the basic coordination gained by practicing some tasks during rehabilitation will

generalize to unpracticed motor tasks the individual will encounter in his/her everyday

life. The concept of "generalization" or transfer allows for the execution of other, related

skills apart from the specific practiced task (new skill or new environment). 7 9 The

critical aspect of generalization of a motor task appears to be whether similar neural

processing requirements of the tasks are incorporated. The more closely linked the









conditions and demands of the new skill or new environment are to the practice

environment, the better the transfer.53' 54 This ability to retrieve information for retention

and generalization is directly linked to practice and the type of invariant features that

constitute the motor skill.9

Choosing the right practice schedule and sequence are dependent on the stage of

learning that the individual is in and the classification of the motor skill that is to be

practiced. When a person who is neurologically intact is learning a new task he/she

begins by gaining an understanding of the rules and strategies inherent in performing the

task. Systems theory suggest that learning the invariant features of the task is

accomplished by engaging coordinative structures (muscles, joints, neural components,

arousal, and gravitational influences).7 31 The learning of a coordinative movement

involves components of the internal and external environment all of which contribute to

the pattern of coordination that emerges. Skilled movements require parameters that

make the task unique and different from other tasks. The unique features contain rules

that are particular to that task. Learning these rules and the invariant features of the task

is often referred to as the cognitive phase of learning.9 Each phase of learning allows for

the complexity of the task to increase and the motor skill to be refined until it is

automatic.

In the early stages of recovery after stroke many people have difficulty initiating

any movement. This lack of movement, related to a decrease of the CMN pool, makes

activation and muscular recruitment a difficult task.55 Rehabilitation post stroke at this

level is concerned with gaining an ability to move, learning the basic interjoint

coordination and activation pattern of muscles, which gives feedback about movement









and how to recruit muscles for motor tasks. In persons post-stroke this stage of learning is

coupled with building the physiological capacity to move and is usually very cognitively

demanding, requiring high levels of concentration.

What do we know about practice and therapy intervention post-stroke? There are

few studies examining motor practice parameters post-stroke. Many of the studies that

are cited in the literature mention practice but fail to elaborate on the specifics of the

practice conditions using traditional therapy as the intervention.2729There are limited

studies on UE practice protocols in stroke that have shown positive results paying

attention to the specifics of practice. Some of these studies have demonstrated that some

of the same principles of motor learning and practice as established in healthy individuals

apply to motor learning post-stroke. Others have not. For example, Hanlon52 1996

studied 24 subjects with chronic hemiparesis to determine the effect of different practice

schedules for the acquisition and retention of a functional movement sequence for the

involved UE. Subjects were randomized into three groups: control, blocked, and random

practice groups. The movement sequence involved a serial task that was alternated with

trials on three other tasks in the random group. The movement sequence was practiced in

two blocks of five trials in the blocked group. A significant difference was found between

random and blocked practice groups with random practice being more effective for

retention over time in individuals post stroke.52 These results in the stroke population

follow the principles of motor learning, retention and transfer in healthy adults.9

In contrast, Cauraugh56 2003 compared blocked and random practice sequences

combined with active neuromuscular stimulation trials in subjects with stroke. The

movements practiced included: wrist/finger extension, elbow extension, and shoulder









abduction. The results indicated motor improvement in both groups without a difference

between the two practice sequences. This study did not support what we know about

contextual interference associated with random practice in healthy individuals.56 It is

difficult to compare these studies as they used different types of tasks. However, the

results of these studies illustrate how little is known about the effects of practice

protocols, type of task practiced, in combination with the level of recovery of the

individual participating in practice. The rules for practice in individuals post stroke are

unclear and the factors affecting the results of practice in this population have not been

established.35 Are the concepts of motor learning based on neurologically intact

individuals relevant when persons post-stroke have difficulty initiating movement and

use pathological synergies to accomplish the movements that they do execute?

Principles of generalization post-stroke have had even less science. First, let's

examine what is known about generalization in healthy individuals in relation to UE

movement tasks. Generalization is an ability to execute another motor task not

specifically practiced. The ability to dissociate a learned motor skill utilizing coordinative

structures and features of the practiced task that are similar to but not part of the practiced

task would be an example of generalization. In a study by Sainburg et al.57 hand

movement directions were reported to generalize for movements made up to 36 degrees

to either side of the trained direction in individuals without neurological deficits.

Generalization beyond the region of training has been documented successfully when a

tight coupling of angle of gaze (visual field) and the position of the hand and shoulder are

provided.58 In both studies, the nervous system demonstrated an ability to use sensory

information to recalibrate the internal model formed by the practiced task. This









recalibration allows for a limited amount of adaptation by the musculoskeletal system to

a novel task. This agrees with our knowledge that the best generalization occurs when

the neural processing requirements are similar to that of the practiced task. Which

parameters of the task that are critical are not clear. Understanding the parameters that

enhance generalization following stroke can contribute to the design of treatment

protocols.

Acquiring interventions that would generalize to skills not specifically trained in

practice sessions (trials) would be advantageous therapeutically. Identifying particular

intervention protocols and pairing them with the stage of recovery or learning that the

individual may be in could enhance their rehabilitation. By building capacity early on in

recovery and layering more complex skills as individuals post-stroke gain an ability to

move could lessen their overall UE disablement. Introducing the right intervention at the

right time may enhance motor learning, retention and generalization.

Bilateral Training

A new approach to UE stroke rehabilitation; bilateral training is beginning to be

investigated systematically and demonstrating some positive results. 16,59-62 Protocols in

these studies have used functional and non-functional tasks practiced bilaterally with

similar temporal and spatial requirements.60 61 63 What do we know about the brain and

bimanual coordination?

Researchers believe that bilateral training may be a good approach in stroke

rehabilitation based on what we know about the brain and bimanual coordination.

Bilateral movements form a tight phasic relationship causing them to perform as a

functional synergy.10' 11The establishment of such coordinative structures during bilateral

movement may serve as a template and entrain the paretic arm during the movement









phase with the uninvolved hemisphere providing a pattern of firing for the involved

hemisphere.64 Generalization of task performance from one arm to the other is not a new

concept. For example, reaching movements generalize from the dominant arm to the

non-dominant arm in healthy individuals.65 How does reaching with one arm improve

function in the contralateral arm? When learning the dynamics of a reaching task the

neural representation for the dominant arm in the contralateral hemisphere may engage

neural elements for both arms. To assess the dependence of generalization on callosal

inter-hemispheric communication, Criscimagna-Hemminger et al.65 further investigated

transfer of the dominant UE to the non-dominant UE in a person with a commissurotomy.

The results were similar with generalization from dominant to nondominant arm

(unaffected UE to affected UE).65 What is the relationship to individuals with stroke?

Conceivably bilateral training may have a similar effect on individuals post-stroke with

improved transfer from the uninvolved UE to the affected UE. Bilateral practice may

also be beneficial because both hemispheres are active during bilateral actions perhaps

activating uncrossed tracts.12-14, 34, 35, 66 Evidence from animal and human research

supports the notion that a temporal interaction between hemispheres occurs in the motor

cortex.

Gerloff et al.15 reviewed the functional coupling of the motor areas of both cerebral

hemispheres during bilateral learning. Interhemispheric interaction is particularly

important during the acquisition phase of the skill.15 Bilateral training may be an

appropriate starting place for rehabilitation after stroke.

There are three studies using repetitive rhythmic bilateral training, which have

demonstrated some transfer effects to other tasks incorporating specific critical elements









of the original training task. In these studies training involved non-functional tasks

performed bilaterally with similar spatial and temporal parameters for each extremity

using "rhythmic" synchronized inphase and antiphase movements. However, many of the

bimanual tasks that are used in daily life require a different contribution from each

extremity. Thus, it is critical to show generalization of this type of training to other useful

coordinative patterns utilized in daily activities as our arms are not always performing

with similar patterns of movement. One of the missing components to our understanding

of this intervention in stroke is generalization of the bilateral training.

The Whitall, et al.61study investigated the hypothesis that bilateral upper extremity

training with auditory cueing of a metronome would improve motor function in persons

who had suffered from stroke. The intervention involved a custom designed arm-training

machine (BATRAC-bilateral arm training with rhythmic auditory cueing), which allowed

for elbow and shoulder flexion and extension coordinated to a metronome set at a self-

selected speed. This study concentrated on a proximal effector system involving

shoulder and elbow joints while limiting trunk forward lean during reaching by a chest

restraint. The design was a single group pilot study with 14 subjects consisting of 20-

minute training sessions, 3 times per week for a 6-week period of intervention with a total

of 18 sessions. Each session consisted of four 5-minute periods alternating inphase and

antiphase movements using the BATRAC interspersed with 10-minute rest periods for

distributed practice. Results indicated significant improvement in motor performance on

the Fugl Meyer (FM) upper extremity section, significant improvement in performance

time on the Wolf Motor Function Test (WMFT) and significant increase in daily use of









the affected extremity on the Maryland Arm Questionnaire for Stroke after six weeks of

training with sustained improvement at 8 weeks after training cessation. 61

In a follow-up study, fMRI demonstrated increased hemispheric activation during

paretic arm movement with changes in the contralesional cortex and ipsilesional

cerebellum after training utilizing the BATRAC.18 Cerebellar activity has been identified

as a principal region for the control of bimanual coordination.14 Although the numbers of

subjects (6) who demonstrated changes in the Luft et al.18 study are small, it is

encouraging data that supports repetitive bilateral training. Bilateral training as a potential

therapeutic intervention has been bolstered by evidence of reorganization of the motor

cortex in individual's using BATRAC post stroke.

Stinear and Byblow 16 had individuals with stroke perform active movement of

the unaffected wrist, which drove passive wrist flexion-extension of the affected UE

using a manipuladum at a self-paced rhythm. Focus was placed on the distal effector

system, the wrist joint. Nine subjects of a heterogeneous group of stroke participants

practiced for 60 minutes a day for a total of 4 weeks with a random assignment into

groups of synchronous and asynchronous practice. Five of the nine participants

demonstrated improvement in motricity scores as measured by the wrist, hand and

coordination components of the upper limb section of the FM Assessment of Motor

Function. Postintervention transcranial magnetic stimulation (TMS) revealed a decrease

in the unaffected cortical map volume in the subgroup of five patients that improved in

motricity. The subjects that demonstrated significant results were a mix of persons with

cortical and subcortical lesions, acute and chronic stroke, mild and severe disability, and

had a combination of synchronous and asynchronous training. The results of this study









suggest that bilateral training promotes a balancing of between-hemisphere corticomotor

excitablility.16

Although these studies have suggested that motor learning has occurred after

bilateral training they have not delineated the parameters or limits of motor skill

generalization with this practice. Schmidt9 suggests that the more similar the neural

demands are during novel tasks the greater the transfer.54 Specifics of the basic neural

elements involved in repetitive bilateral training for individuals post-stroke have not been

assessed in a transfer test. There are only a couple of studies on bilateral coordination

that delineated parameters important for generalization of a novel task in individuals who

were neurologically intact.67'68

Little is known about the principles of generalization of bilateral coordination in

healthy individuals except the studies mentioned above and to date there is nothing in the

literature involving the stroke population. In neurologically intact individuals Temprado

and Swinnen demonstrated generalization of a bilateral coordination pattern to a novel

pattern when the spatial relative phase (RP) (a variable that characterizes the spatial

relationship between two limbs) of the transfer task was similar but not to a task with a

different spatial RP.67 Muscle synergies engaged during interlimb coordination tasks are

influenced by spatial orientation. The symmetry of movement may be an important

factor in improving coordination in bilateral tasks.68 Determining the relationship of

training task parameters (spatial, angle of gaze, joint angles) to generalization in

individuals post stroke has not been specifically investigated.

Biomechanics of Reaching

Reaching is a functional task that requires control of multiple joints through

space.69 Kinematic measures of reaching have been utilized in studies of generalization to









document change in the pattern of reaching.58' 67,70 Biomechanical evaluations are

capable of capturing interjoint coordination, and movement composition thus indicating

quality of the reaching pattern.69 71 72 Biomechanical measures assessing temporal

aspects of reaching include but are not limited to; movement time, time to peak velocity,

peak velocity which indicates symmetry of the reach, strategy for reaching, and

acceleration. Kinematic spatial parameters of reaching include hand path trajectory (how

straight is the path to the target) during the reach.71 The literature on the biomechanics of

reaching has documented that reaching post-stroke is slower, discontinuous with many

movement reversals (stops and starts during the movement to the target), and the

trajectories are curved to the target.69' 71-73 Reliability and validity of these biomechanical

measures in the stroke population are not established to date.71 However biomechanical

assessment of reaching may provide an understanding of motor control and assist in the

evaluation of new therapies.

Summary

Motor learning and neuroplasticity are dependent on practice. The appropriate

type, duration, intensity, and frequency of practice to enhance motor learning,

generalizability, and motor recovery have yet to be determined in the stroke population.

What parameters should be emphasized in rehabilitation during practice sessions to

maximize generalization? It is not clear if task specific training is important in laying a

foundation for coordinative movement in persons after stroke. Persons post stroke have

difficulty moving and must relearn coordinative patterns to execute motor tasks. Perhaps

the focus should be on engaging coordinative structures that might provide a general

motor template to build physiological capacity and complex movements. Establishing a

motor capacity to move post stroke may provide the framework for generalization of a









practiced task. Supportive evidence on bilateral training and generalization suggests that

engaging similar spatial and temporal synergies may have positive effects on motor

learning in persons post stroke.16, 18, 61, 63, 67, 68, 70

Utilizing Whitall's protocol for repetitive bilateral training: can a "general

framework" of coordinative synergies be created divorced from a particular skill or task

that would underlie the basics of motion and movement capabilities? Whitall's protocol

used an arm training machine (BATRAC) for repetitive bilateral training in one

orientation with inphase and out-phase movements. The repetitive movement of the UE's

in this protocol engages similar synergies as real life reaching tasks bilaterally

accomplished in the workspace directly in front of the person. Stinear and Byblow using

a distal effector system demonstrated a balancing effect between hemispheres of

corticomotor excitability. How functional is repetitive bilateral training and to what

degree if any will this type of training assist an individual with stroke to execute tasks

that were not specifically trained but similar?

Therapy interventions have focused on simulation of tasks that would be performed

in the home and community. Therapists have emphasized building a repertoire of

movement skills that incorporate components necessary for other unpracticed motor

skills. Practicing every task that will be encountered by an individual once they are

discharged from rehabilitation is impossible. Identifying intervention protocols that

generalize to tasks unpracticed in the rehabilitation arena is essential. Generalization of

learned motor skills would enhance a person's ability to participate in life roles at home

and in the community by increasing the number of conditions and solutions to a host of

motor problems. Bilateral training may lay a foundation in individuals post-stroke for









engaging coordinative structures allowing the execution of "basic" motions and

movement even though the practice is not variable or with real life tasks. Collecting

kinematic data for assessment of generalization of this training may help us to understand

which reach parameters might change after bilateral training. Repetitive bilateral training

is distributed blocked practice, which avoids fatigue but allows for the criteria of the skill

to be learned without building endurance. This combination of practice may build a

"physiological capacity" for movement in persons post-stroke. The entrainment of both

hemispheres during bilateral training provides a functional coupling of the motor cortexes

especially during the acquisition phase of learning a bilateral task.15 Yet, the ability of

such training to transfer to functional tasks awaits testing.

The aim of this study is to determine if repetitive rhythmic bilateral training (using

the BATRAC as outlined in the Whitall et al.61 study) will generalize to a novel task that

is performed with similar neural demands.

Specific Aims

To test the hypotheses that repetitive bilateral training using blocked-distributed

practice will demonstrate spatial generalization to a novel task with similar neural

demands in joint angles, workspace, visual gaze angles, and muscle timing. The

following research questions will be addressed in a single group repeated measures

design employing a pre-test and post-test period. Outcome measures will be taken prior to

intervention and at the end (completion) of 2 weeks of proximal repetitive bilateral

intervention.









Research Aims and Hypotheses

General aim 1

To determine spatial generalization to a novel task after proximal bilateral training

for the affected upper extremity.

Specific aim la and lb

la. To determine if proximal bilateral training generalizes to a novel task (#1) that

is similar in shoulder/elbow joint angles, constraints of muscles and joints (coordination),

visual gaze angles and a workspace identical to the training.

lb. A secondary novel task (#2) will be tested with different joint angles, visual

gaze angles and workspace from the training motion.

Primary hypotheses la and lb for spatial parameter

la. Generalization will occur for novel task (#1) when tested in the same workspace

with similar joint angles as practiced for the proximal bilateral training intervention. At

the end of week two of proximal bilateral training: kinematic data for hand path trajectory

to the target. will demonstrate generalization for novel task (#1). Data will be compared

to baseline data with improvement for the above kinematic outcome predicted. Hand

paths to the target in stroke are variable and lack continuity..69 71,72 Therefore, based on

the literature hand path trajectory will be straighter. lb. Generalization will not occur for

novel task (#2) that is dissimilar in joint angles and workspace to training. At the end of

week two of proximal bilateral training: kinematic data for hand path trajectory will not

generalize for novel task (2#). Data will be compared to baseline data with no

improvement for the above kinematic outcome predicted.









Secondary hypotheses 2a and 2b for temporal parameters

Temporal parameters are assessed separately in this study because neither the

training nor the testing tasks emphasized speed. Therefore these parameters may not

change. Individuals post-stroke do move slower when compared to healthy individuals

so it is possible that the speed may be different after intervention although it was not

emphasized.69

2a. Improvement in movement time, time to peak velocity, peak velocity and

acceleration will occur for novel task (#1) when tested in the same workspace with

similar joint angles as practiced for the proximal bilateral training intervention. At the

end of week two of proximal bilateral training: kinematic data for movement time, time

to peak velocity, peak velocity and acceleration (the percent of the reach that is

acceleration) will change. Data will be compared to baseline data with improvement for

the above kinematic outcomes predicted. Individuals post-stroke move slower during

reaching and often demonstrate a skewed profile in reaching with a shorter relative

duration in the acceleration phase, peak velocity is often lower compared to healthy

individuals and absolute time to peak velocity is shorter.69' 71Therefore, based on the

literature movement time will decrease, time to peak velocity will increase, peak velocity

will be higher and the percentage of reach that is acceleration will approach 50% of the

acceleration curve.

2b. Improvement in movement time, time to peak velocity, peak velocity, and

acceleration will not occur for novel task (#2) that is dissimilar in joint angles and

workspace to training. At the end of week two of proximal bilateral training: kinematic

data for movement time, time to peak velocity, peak velocity, and acceleration (the

percentage of the reach that is acceleration) will not change for novel task #2. Data will






24


be compared to baseline data with no improvement for the above kinematic outcomes

predicted. Movement time, time to peak velocity, peak velocity, and the percentage of

reach that is acceleration will not improve.














CHAPTER 2
METHODS

Experimental Design

This study employed a single group, repeated measures design that included a pre-

test baseline and post-testing at the completion of two weeks of proximal bilateral

training.

Subjects

Fifteen participants with hemiparesis and UE motor deficits were recruited from

the Brain Rehabilitation Research Center's stroke database at the North Florida/South

Georgia Veterans Health System. One subject dropped out of the study due to unrelated

medical reasons. This database consists of individuals with stroke who have been

recruited to participate in rehabilitation studies from the North Florida/South Georgia

VA, Shands Hospital at the University of Florida, Shands Rehabilitation Hospital, Shands

Hospital at Jacksonville, Brooks Rehabilitation Hospital and the Brooks Center for

Rehabilitation Studies in Jacksonville. Nine of the subjects were male and 5 were female

with a mean age of 64.4 (sd = 13.3) years and a mean of 5.5 (sd = 3.9) years post-stroke.

Five of participants had right-sided lesions and nine had left-sided lesions. Demographic

and clinical data for the subjects are summarized in Table 2-1. Whitall1, Luft,2 and

Stinear and Byblow3 all demonstrated treatment effects with sample sizes of 9-14

subj ects.

Inclusion criteria were: 1) single unilateral stroke at least 6 months prior, 2) no

active drug or alcohol abuse, 3) able to follow 2-step commands, 4) no history of a









clinical ischemic or hemorrhagic event affecting the other hemisphere, and no CT or MRI

evidence of more than a lacune or minor ischemic demyelination affecting the other

hemisphere, 5) no history of more than minor head trauma, subarachnoid hemorrhage,

dementia, learning disorder, drug or alcohol abuse, schizophrenia, serious medical illness,

or refractory depression, 6) some active movement in shoulder and elbow with palpable

extrinsic forearm finger muscle recruitment. Exclusion criteria: 1) no movement in UE

or no palpable muscle recruitment in extrinsic finger extensor muscles, 2) scores > 3 on

the Motor Activity Log, indicating a high level of UE function, 3) spasticity greater than

2 on the Modified Ashworth Scale.

Each participant gave informed consent according to University of Florida

Institutional Review Board and North Florida/South Georgia Subcommittee for Clinical

Investigation requirements prior to participation.

Procedure

UE motor function for novel task (#1) and (#2) was tested at the beginning of the

baseline period prior to intervention and after two weeks of proximal bilateral training.

All participants performed a session of baseline testing immediately prior to starting the

intervention (see Outcome Measures section below). The two-week intervention period

was followed immediately by post-testing of UE generalization of training to a novel

task. As in Whitall et al.,1 training was provided for 18 hours. However believing that

intensity is important,46 these hours were provided in 8 sessions of 2.25 hours each

across 2 weeks for a total of 18 hours. Short term upper extremity practice has been

shown to be effective in improving upper extremity motor function in persons post-

stroke.7' s









Table 2-1. Subject demographic data
Subject Age Gender Years Side of Lesion site Fugl-Meyer*
(years) poststroke Lesion Pre
sd= 13.3 sd 3.9


80 M


49 M






80 F



59 M

62 M
68 M
40 F

72 M

67 F


67 M


80 M


38 F





64 F


1






3.5



7.4

5.4
11
5.5

11.3

4.7


4.8


1.7


1.8




3.8


13.5


L CVA L MCA,
parietal/post
frontal
L CVA L subcortical
infarct w/
hemorrhage
conversion-basal
ganglia internal
capsule
R CVA R MCA
hemorrhage,
hematoma R
basal ganglia
R CVA R MCA ischemic
event
R CVA R MCA posterior


RCVA
LCVA


R cortical infarct


L putamen


hemorrhage
L CVA L MCA posterior
infarct
R CVA R superior hyrus,
striatocapsular
infarct
L CVA L frontal lobe
hemorrhage
w/atrophy
L CVA L subcortical
lacunar
periventicular
L CVA L MCA infarct,
deep white matter
insula frontal
lobe, cortex F/P
junction
L CVA L infarct insula
F/Temp/P
convexity
L CVA L MCA infarct


*Based on Fugl-Meyer scale (maximum score) =66,
CVA= cerebrovascular accident









Proximal bilateral training: The proximal bilateral exercise was identical to that

performed in the study by Whitall and colleagues.1 In this paradigm, participants were

seated facing a table on which was placed the arm training machine-BATRAC consisting

of two paddles mounted in nearly frictionless tracks.' The handles of the device are

horizontally oriented and cylindrical in shape. The participants grab the handles of the

paddles (with the affected hand strapped on as needed) and move the handles back and

forth in a rhythmic manner for 5-minute blocks with 10-minute breaks between blocks to

minimize fatigue. There was a chest plate that prevented the participant from leaning

forward with trunk flexion when the handles were pushed away from the person's body.

This chest plate was set at a distance of six inches from the table and the participant was

asked to keep his/her trunk against this plate during the intervention periods. The distal

stop on the BATRAC was lined up to the metacarpalphangeal joint (MCP) when the

intact arm and fingers were extended directly in front of the body over the track. This

corresponded to 80% of the reach. When active range of motion was limited at the elbow

joint the distal stop on the BATRAC was set at the wrist joint initially and progressed to

the MCP joint the second week. For half of the blocks, the participants moved the

handles symmetrically (in-phase); while in the other half of the blocks the participants

moved the handles 180 out of phase. These trials were alternated and balanced across

subjects and sessions. Because movement of one paddle is independent of the other

paddle, participants had to coordinate the movements of both UE's in order to achieve the

correct temporal and spatial movement relationships. Participants were encouraged to

move the full range of the exerciser and were assisted as needed by the researchers.

Participants were asked to assume a comfortable self paced movement speed at the first









session, which was maintained throughout the daily training session with the use of

auditory cues provided by a metronome set at the self-selected frequency. The

metronome was set at the beginning of each day of training to the participant's

comfortable pace to prevent holding the individual back from making progress.

Object 2-1. BATRAC Inphase.

Object 2-2. BATRAC Antiphase

Outcome Measures

The primary hypothesis stated that in individuals with chronic stroke, bilateral

training would generalize to a novel task that was similar in neural demands to the

training but not to the dissimilar novel task. The dependent variables were divided into

primary and secondary based on differences in spatial and temporal parameters. Knowing

from the literature that movements in the upper extremity are affected by abnormal

synergies post-stroke, we believed that the intervention (synchronous and alternating

movements bilaterally) would effect the spatial parameter to a greater extent than

temporal parameters by breaking up the abnormal synergies through more normal

interlimb coupling.8' 9 Therefore, the primary goal was to assess spatial generalization

after bilateral training. The primary spatial dependent variable was HPT. The secondary

hypothesis stated that bilateral training would improve the temporal dependent variables

(MT1, MT2, TPV, PV and acceleration) after 2 weeks of intervention. The procedures

for testing pre- and post-intervention follow.

Kinematic analysis of reaching

Participants were seated on a bench with the hip and knee angle at 90 degrees and

the feet flat on the floor. Each participant was asked to position their buttocks and back

against a straight edge held behind them to assure the same start position on the bench









each testing period. The affected UE was positioned at rest, palm down, on a table placed

in front of the person at the same distance as the intervention table including the chest

plate distance of six inches. The UE was in neutral shoulder flexion/extension, rotation

and adducted. The elbow was flexed as in the start position for the arm-training machine.

Novel Task #1(Similar)

The start position on a table in front of them was identical to the start position used

for the training with the BATRAC however the arm-training machine was not used

during novel task #1 nor was there a chest restraint. End targets at approximately 80% of

reach were marked on the table at the same arm reach length (elbow extension in front of

the body as measured to the metacarpalphalangeal joint or wrist joint determined during

intervention) as in the arm-training machine (BATRAC). A reflective marker was placed

on the target so the vicon motion analysis system could pick up the end point.

Participants moved their arm and hand to the target and returned to the start position five

times (Figure 2-1). The participants were not asked to point to the target but to simple

reach to the target. To minimize fatigue, there was a 30 second rest break between

reaches.




STarget 0










Figure 2-1. Illustration of testing conditions for similar spatial orientation novel task #1
(similar task)









Novel Task #2(Dissimilar)

The start position was on a table aligned with the paretic shoulder directly in front

of the subject's body at the same distance from the trunk as in the BATRAC during

intervention. The subjects were asked to move their arm and hand to a target on the table

that was aligned horizontally with the start position and with the non-paretic shoulder at

the near edge of the table and then return to the start position five times (Figure 2-2). A

reflective marker was used so that the vicon motion analysis system could pick up the

end point. There was no trunk restraint used during this testing condition. To minimize

fatigue, there was a 30 second rest break between reaches.








0 Target







Figure 2-2. Illustration of testing conditions for dissimilar spatial orientation novel task
#2 (dissimilar task)


Kinematics of reaches were videotaped using a 3-D movement recording system (8

camera Vicon system). Retro-reflective markers were placed on C7 and T10 vertebrae, the

acromion process, clavicle, sternum, upper arm, lateral epicondyle of the elbow, medial

epicondyle of the affected UE, forearm, wrist condyles, dorsum of the hand, MCP joint of









the index finger, and the index fingertip of the affected UE. The data was collected at 100

Hz. All data was averaged using the middle 3 trials for each novel task.

Kinematics were analyzed for hand path trajectories (end point paths measuring

straightness of the hand path), movement time, time to peak velocity, peak velocity and

acceleration as in Cirstea, et al., Cunningham et al., and McCrea et al.9-12 Posteriori

analysis of the velocity profiles to assess movement smoothness changes were performed

as described by Rohrer et al.13

Primary Spatial Dependent Variable

1. To determine hand path trajectory (HPT), the ratio of the length of the actual path

traveled by the index finger in three-dimensional space to the length of an ideal straight

line joining the initial and final index finger positions was computed. If the participant

was unable to extend the index finger, the trajectory was measured from a marker on the

metacarpalphalangeal joint of the 2nd digit. The length index rather than the more usual

perpendicular distance between the trajectory better captures trajectories that may deviate

from the ideal straight line and may even intersect with that ideal line. Reach accuracy

was computed as the root mean squared error of the absolute distance between the final

endpoint position and the position of the target.

Secondary Temporal Dependent Variables

Temporal parameters in reaching post-stroke are significantly slower than healthy

adults.10-12 Therefore, although subjects were not asked to reach as quickly as possible

during the testing tasks, the predictions are based on the assumption that the training

intervention would increase their usual speed.

1. Movement time was the difference in time from movement onset to movement

offset. Movement time 1 (MT1) was defined as the onset of movement from the start









position to the touch of the target. A mark was made with tape to delineate the start

position and target area based on the intervention position of the BATRAC arm-training

machine. Movement time 2 (MT2) was defined as the movement onset from the target

back to the start position. 2. Time to peak velocity (TPV) was a measure of absolute

time measured in seconds from the point of movement onset to peak velocity.

3. Peak velocity (PV) corresponds to a moment in time when the highest velocity is

reached where acceleration is at or near zero at the changeover from the acceleration to

the deceleration phase. PV is calculated from the rate of change over time.

4. Acceleration was calculated from the slope or inclination of the velocity curve and

includes the percent of reach within this curve. Acceleration corresponds with the time

period of movement onset to peak velocity.

Posteriori of velocity profiles

The following metrics were analyzed posteriori to assess the movement smoothness

of the velocity profiles during the novel reaching task pre- and post-test.

1. Jerk metric was calculated from the average value of the absolute jerk divided

by the peak velocity of the corresponding trial (Jerk is defined as the rate of change of

acceleration). Jerk metric is assigned a negative value so as the smoothness increases, the

jerk metric also increases.

2. Speed metric was calculated from the average velocity divided by the peak

velocity of the corresponding trial. As the smoothness increases, speed metric also

increases.

3. Movement arrest period ratio (MAPR) was the amount of time that the

velocity profile was less than 10% of the peak velocity divided by total time of the trial.

A smaller MAPR indicates a smoother velocity profile.









4. Peaks metric was the number of peaks in the velocity profile greater than

0.5m/s multiplied by negative 1. As the smoothness increases, the peaks metric increases.

5. Tent metric was calculated from the area under the velocity profile curve

divided by the area of a curve draped over the top of it. The closer tent metric is to 1, the

smoother the velocity profile.

Data storage conformed to HIPAA regulations. VICON-captured data was stored

in a database on a secure network. Participants were assigned a participant number and

this number was the only identifier stored on these databases. A list of the participants'

names and participant numbers was kept in a locked file in Dr Lorie Richard's office.

Only the investigator and Dr Richards had access to this list. Only study personnel had

access to the participant notebooks or the database.

Data Analysis

For each dependent variable a repeated measures 2 (time) x 2 (task) ANOVA was

performed with an alpha level of .05. Greenhouse-Geisser's adjustment of degrees of

freedom was applied to correct for small departures from the assumption of normality

and equality of variance in the two-factor design. A Bonferroni correction factor was

used to correct for multiple analyzes for the primary and secondary dependent variables.

The corrected alpha level for the primary dependent variables was .05, secondary

dependent variables was .01, and .01 for the posteriori analysis of the metrics. Lastly, a

descriptive analysis of the individual data was performed post-hoc. The sample of this

study was made up of a heterogeneous group of individuals with various levels of

severity at baseline; therefore we decided to examine the data descriptively at the

individual level, conjecturing that this could provide information on subgroups of






35


individuals that may have benefited, but would not have been detected in the group

analyses.














CHAPTER 3
RESULTS

Data Analysis

Kinematic outcomes were analyzed with a repeated measure ANOVA for each of

the primary dependent variables. The within subjects factors were time (pre-test/post-test)

and task condition (novel task #1 and novel task #2). The primary dependent variable was

hand path trajectory. The secondary dependent variables were: 1) movement time, 2) time

to peak velocity, 4) peak velocity and 5) the percentage of the reach that was

acceleration.

An alpha value was set at .05 and corrected with Bonferroni to account for multiple

analyses on the secondary and posteriori analysis. The corrected alpha levels on

dependent variables were .01 for the secondary and the posteriori analysis of the velocity

profiles. Individual data will be reported last to identify individual differences that may

account for a pattern in the data.

Primary Spatial Dependent Variable

Table 3-1 displays the means and standard deviations for all outcome measures for

primary and secondary dependent variables. Table 3-2 displays the ANOVA summary

table.

Hypothesis la and lb HPT will become straighter after intervention for novel task

#1 (generalization of similar task). No change will be noted for HPT on novel task #2 (no

generalization to dissimilar task).









Hand path trajectory

HPT was calculated as the ratio of the actual path traveled to the ideal straight line

joining the initial and final positions for the index finger or metacarpalphalangeal joint of

the 2nd digit (when subjects could not extend the index finger). There was a significant

main effect of time for HPT with hand path trajectories straighter at posttest (Figure 3-1).

However, there was no main effect of task nor interaction between the two variables. The

increase in straightness was found for both novel task #1 and novel task #2. Therefore

control of the spatial parameters of reach gained with intervention generalized to both

similar and dissimilar tasks.

Secondary Temporal Dependent Variables

The main effects are reported below and means and sd are displayed in Table 3-1. The

ANOVA summary table for the secondary dependent variables is displayed in Table 3-3.

Hypothesis 2a and 2b Generalization to novel task #1 following intervention will

be evident with decreased movement times. No improvement in movement times will be

demonstrated on novel task #2.

Movement time

Contrary to expectations, the time to touch the target (MT1) was not significantly

different post compared to pre-intervention, nor across tasks. MT2, although shorter for

novel task #1 compared to novel task #2, also did not change with intervention

(Figure 3-2). There were no significant interaction effects of time and task on either

variables.

The data for MT1 and MT2 did not support the hypothesis that there would be

improvement in motor control on an untrained task with similar joint angles to the

training task. Movement time at post-test was no shorter than at pre-test. Bilateral









training did not appear to improve motor control during the performance of a task that

was similar in terms of joint angles to the training task. Not surprisingly, no

improvements in movement time were found for novel task #2, a task with dissimilar

joint angles to the training task which was in support of the hypothesis.

Hypothesis 2a and 2b TPV will increase for novel task #1 following intervention:

TPV will not change with novel task #2.

Time to peak velocity

TPV was measured from the point of movement onset to peak velocity. There was

no difference in TPV across time or tasks. There were no significant interaction effects.

Therefore, the training had no effect on the TPV.

Hypothesis 2a and 2b: PV will increase for novel task #1 and will not change for

novel task #2 following 2 weeks of intervention.

Peak velocity

PV was the highest velocity that occurred during the reach. It typically occurs at the

moment of changeover from acceleration to deceleration in reaching to a target. There

was a significant main effect of time for PV (Figure 3-3) with PV larger following

intervention for both novel tasks. There was no main effect of task nor interaction

between time and task. Therefore, generalization of training was seen for similar and

dissimilar tasks.

Hypothesis 2a and 2b The acceleration phase of the reach will approach 50% of

the curve for novel task #1 and will not change for novel task #2 following 2 weeks of

intervention.









Acceleration

There were no main effects or interaction effects noted for percentage of the reach

in acceleration.

Posteriori of velocity profiles

Although this analysis was performed posteriori, changes in the smoothness of the

velocity curve could be beneficial in interpreting data collected on the reaching pattern of

individuals post stroke. An ANOVA summary table for the post hoc analysis is displayed

in Table 3-4.

Changes in the metrics of the velocity profile would point toward a smoothing of

the velocity curve following intervention indicating fewer stops and starts in the reaching

pattern toward the target. Smoothness of the curve would infer that the coordination of

the motor pattern for reaching has improved. There was a significant main effect of time

for the Peaks Metric with improvement post-intervention however no main or interaction

effects for task (Figure 3-4). In addition, there were no main or interaction effects for the

remaining smoothness metrics.

Descriptive Individual Data

Although this analysis is posteriori, this individual data could be beneficial in

planning future trials. Table 3-5 displays the individual data pattern of change across

primary and secondary variables for each subject.

Individual differences were analyzed comparing the raw score difference from pre-

to post-test with the pre-test sd for each dependent variable. Individuals who

demonstrated a change at post-test greater than the sd for the dependent variables at pre-

test are reported below. No subject improved in all variables with intervention.

Interestingly in three of fourteen subjects no change for any dependent variable was









noted and 4/14 subjects demonstrated a change in only one dependent variable. Five of

fourteen subjects demonstrated differences greater than the sd of the pre-test on three or

more variables. Thus, the descriptive individual data shows no general pattern across

subjects or subsets of subjects. Training did not frequently foster change in similar tasks

(novel task #1), but sometimes did in dissimilar tasks (novel task #2). In actuality change

was infrequent across the board.

Object 3-2. Testing conditions for generalization indicated some individuals changed.
Pre-test.

Object 3-3. Testing conditions for generalization indicated some individuals changed
Post-test









Table 3-1. Displays the means and standard deviations (sd) for task condition # 1 and #2
for all dependent variables pre- and post-intervention.


HPT Pre
Post




MT1 Pre
Post



MT2 Pre
Post



TPV Pre
Post


Pre
Post


Accel Pre
Post


Task #1
Similar
Mean (sd)

1.500 (.348)
1.519 (.298)


2.050 (1.692)
1.976 (2.30)


Task #2
Dissimilar
Mean (sd)

1.406 (.350)
1.264 (.114)


1.620 (.749)
1.275 (.512)


1.913 (.837)
1.666 (.885)


2.838 (2.552)
2.139(1.828)


.446 (.190)
.368 (.618)


.431 (.153)
.403 (.153)


.432 (.151)
.497 (.284)


.332 (.213)
.317 (.147)


.1.146 (1.389)
.887 (.258)


.314(.112)
.374 (.153)









Table 3-2. Summary ANOVA model for the primary dependent variable. Significant p-
value = 0..05

Dependent variable after two weeks of intervention
Source Mean Square F (1,13) p-value

HPT Time .426 8.132 .014
Task 5.197 1.700 .215
Time*Task 9.072 .901 .360






Table 3-3. Summary of ANOVA model the secondary dependent variables. Significant p-
value = 0.01.

Dependent variables after two weeks of intervention
Source Mean Square F (1,13) p-value

MT 1 Time 4.48 2.248 .158
Task .614 .726 .410
Time*Task .260 .280 .606

MT 2 Time 6.84 1.897 .192
Task 3.14 8.167 .013
Time*Task .714 1.076 .319

TPV Time 1.491 .126 .728
Task 4.022 3.439 .086
Time*Task 1.143 .659 .427

PV Time 4.274 8.205 .013
Task .130 .212 .653
Time*Task .767 .767 .397

Accel Time 5.207 .392 .542
Task 6.864 1.114 .311
Time*Task 1.931 1.590 .229










Table 3-4. Summary ANOVA model for posteriori analysis
Significant p-value = 0.01.
Source Mean Square F (1,13)


Time
Task
Time*Task

Time
Task
Time*Task

Time
Task
Time*Task

Time
Task
Time*Task

Time
Task
Time*Task


1481.091
659.802
415.415


2.829
1.033
.333

2.888
3.663
.595

.007
.477
.396


Jerk
Metric


Speed
Metric


MAPR




Peaks
Metric


Tent
Metric


16.476
.470
.376


1.053
.093
2.021


of velocity profiles.

p value


.116
.328
.574

.113
.078
.454

.936
.502
.540

.001
.505
.550

.324
.765
.179


2.5885
1.355
8.377

1.779
1.525
2.500

4.767
4.939
1.796

4.408
1.475
4.378


I











Table 3-5. Summary of individual change at post-test greater than the pre-test sd for each


dependent variable (x > sd)
Subjects FM-UE MT1 MT2
Pre/nost


TMT TPV


HPT Accel


1
Task #1 24/28 X
Task #2 X X X
2
Task#1 51/49 X X X X
Task #2 X X X
3
Task #1 48/44
Task #2
4
Task#1 33/38 X
Task #2
5
Task #1 51/53
Task #2
6
Task #1 46/45 X X X
Task #2 X
7
Task#1 37/38 X X
Task #2 X
8
Task #1 59/62
Task #2 X
9
Task #1 64/59
Task #2
10
Task #1 52/61 X
Task #2 X X
11
Task #1 43/45 X
Task #2 X X
12
Task#1 35/34 X X X
Task #2 X

13
Task #1 18/23
Task #2 X X
14
Task#1 33/35
Task #2 X
% Change
Task 1 2/14(14%) 1/14 (7%) 1/14(7%) 5/14(36%) 3/14(21%) 2/14(14%) 2/14(14%)
Task 2 2/14(14%) 1/14(7%) 2/14(14%) 5/14(36%) 2/14(14%) 0/14 (0%) 4/14(29%)












Hand Path Trajectory


1.600



1.500
1.453

1.392
1.400



1.300



1.200



1.100



1.000
HPT pre-test 1 HPT post-test


Figure 3-1. Significant main effect displayed for HPT for post-test. A value of 1 equals a
straight line.








46




Movement Time 2


3.500



3.000


2.500



2.000



1.500



1.000


0.500



0.000


2.489


1 MT2 novel task #2


Figure 3-2. Significant main effect displayed for MT2 novel task #1.


1.789














VTT2 novel task #1













Peak Velocity


0.800


0.700


0.600


0.500
-c

a 0.400
o
0


0.300


0.200


0.100


0.000


0.562


S0.669


PV pre-test 1 PV post-test


Figure 3-3. Significant main effect displayed for PV on the post-test.








48






Peaks Metric


-0.82

-0.77

-0.72

-0.67

-0.62
-0.57

-0.52

-0.47

-0.42

-0.37

-0.32
-0.27

-0.22

-0.17
-0.12

-0.07

-0.02


I T -0.761


- 0.702


pre-test post-test

Figure 3-4. Significant main effect displayed for posteriori Peaks Metric post-test.














CHAPTER 4
DISCUSSION

Generalization is the ability to perform similar motor skills that were not

specifically practiced as part of the training intervention. Generalization is directly related

to the amount of practice on a particular task and how much motor learning occurred

during the acquisition phase of the new the task. In addition, for neurologically intact

individuals learning specific motor patterns, generalization occurs only under highly

similar spatial conditions that have similar neural processing elements and demands.1-3

We do not know if this is also true for the basic coordination skills that persons relearn

after stroke. Persons post-stroke are just regaining the capacity to move and learning how

to perform tasks with a decreased CMN pool output often their movements are influenced

by pathological synergies. The critical components of invariant task features necessary

for generalization of a motor skill in individuals with stroke under these conditions have

not been clearly delineated in the literature. 1

The specific aim of this study was to test spatial generalization of repetitive

rhythmic bilateral training to two novel reaching tasks in individuals with stroke. The

training task was a set of repetitive continuous movement reversals constrained by the

BATRAC equipment which allowed only reaching forward in front of the body within a

limited range (80% of the available reach). The transfer task (novel task #1) had similar

neural demands for joint angles, workspace, visual gaze angles, and muscle timing

compared to the training task but was not performed on the BATRAC. The second

transfer task (novel task #2) had dissimilar joint angles, workspace, and visual gaze









angles to the training task. It was predicted that improvements in kinematic parameters of

movement gained through two weeks of intervention would generalize to the similar

novel task #1 at post-test but not to the dissimilar novel task #2. Generalization occurred

at post-test for HPT but surprisingly was equivalent across the similar and dissimilar

tasks.. Generalization of training was further supported posteriori by the Peaks Metric

that was also significant at post-intervention. The changes in dependent variables taken

together indicate improved coordination with decreased stops and starts in the novel

reaching tasks.

We also predicted that movement speed might also improve with training. In fact,

peak velocity was also significant at post-test, with similar changes noted for both testing

tasks. Perhaps, novel task #1 and novel task #2 did not present task features that were

dissimilar enough to delineate a change between them kinematically post-intervention

The remaining temporal dependent variables of MT1, MT2, TPV, and acceleration

did not generalize to either task. The lack of change in these particular temporal

parameters may have been because speed of movement was not emphasized in the

training or testing tasks. On the other hand, the higher PV suggests that for at least some

of the reach, movements were faster. Perhaps subjects moved faster during parts of the

reach, but slowed their movements in the remaining sections of the reach, resulting an

overall unchanged movement time. Only a more detailed analysis of the reaching strategy

would allow firm conclusion on this issue. Thus, the results of this study offer only weak

evidence that repetitive rhythmic bilateral training may generalize to untrained tasks.

Unfortunately there was no measure of actual intervention task learning in this study to

delineate the lack of motor learning from the lack of generalization. Instrumentation of









the BATRAC equipment would allow for measurement of the temporal coordination of

the UE's providing more accurate measures of motor learning on the training task. This

information could then be utilized to make further assumptions about motor learning of

the intervention task compared to generalization of the novel transfer task.

Neuroscience Rationale for Repetitive Rhythmic Bilateral Training

The rationale for the potential of the BATRAC as an UE training tool post-stroke

has been theorized to tap into basic neurophysiological mechanisms that stimulate

coordinative structures priming the nervous system and firing up the CMN pool. Studies

have shown activation of both hemispheres with bilateral movements that are organizing

in a tight phasic relationship.4-8The symmetrical temporal relationship between the

hemispheres during bilateral activities may assist in laying down a template for basic

movement components necessary for reaching. However, neither the specific movement

characteristics of bilateral practice necessary for generalization nor the level of severity

of individuals post-stroke that would be most responsive to this type of therapy have been

determined.9

The inconclusive findings of this present study are in contrast with the preliminary

data regarding bilateral utilization presented in the literature.10' 11 Using the BATRAC,

Whitall et al.,10 demonstrated significant improvement in UE motor performance on the

FM and WMFT. The results in the Whitall et al.10 study could be interpreted as

generalization to untrained tasks since the items on these testing measures were not

trained specifically in the bilateral intervention.

Luft et al.11 showed that repetitive rhythmic bilateral training using the BATRAC

influences neural mechanisms underlying motor skill in a small number of subjects. They

found increased hemispheric activation during paretic arm movements after training.









Although the motor skill assessed by fMRI in this study was not a reaching task as was

the transfer task in the present study, increased activity of the contralesional hemisphere

was observed. The Luft et al.11 study suggests that the BATRAC intervention induces

reorganization of motor networks in persons post stroke and Whitall's10 work further

suggests that reaching post bilateral intervention may improve.

Differences in our subject population and the kinematic parameters selected as

dependent variables could account for the different results observed in this study. Whitall

et al.10 used the FM and the WMFT to measure efficacy of bilateral training. These

assessments are a composite of summary scores over multiple items. Looking more

closely at the items that make up the assessments reveals that some items increase and

some items do not, while other items may even decrease a little. Therefore the overall

score can show improvement, while individual items themselves may not. This study

focused on the kinematic measures of one single task only 2 tasks, one that was similar to

the bilateral training. It is hard to compare the results of performance on only 2 tasks

with summary scores on tests made up of many tasks. Perhaps had we chosen different

tasks, we would have also found improvement across our subject sample. The task that

was chosen demonstrated variability between subjects and overall did not show change

across the multiple dependent variables, perhaps a different task or set of tasks may have.

Ideally a combination of clinical, kinematic, and kinetic measures would give a more

complete understanding of movement behaviors. Therefore, it is difficult if not

impossible to compare the results of the Whitall et al.10-12 studies with the present study

due to the differences the nature of the outcome measures.









Factors Potentially Affecting the Study Results

Practice schedules are known to affect motor learning, and could possibly have

played a role in our results.13, 14 This study utilized a distributed model of practice as did

Whitall et al.10 Distributed practice allows for a rest period equal to or greater than the

intervention period. In this study the intervention period equaled 5 minutes and the rest

period 10 minutes. Studies by Lee and Genovese15 have demonstrated in healthy

individuals that transfer performance was increased for groups that had longer rest

periods versus work periods. Other studies have also shown that distributed practice has a

large positive effect on learning.16, 17

The intervention in this study was also delivered in a blocked manner (grouping

like trials together) however, while blocked practice improves acquisition of a task,

random practice appears to be superior for true learning: retention and generalization of

the skill when tested after the training period of an intervention.18-20 Although, Whitall et

al.10 demonstrated improved upper extremity functional measures with this type of

practice (distributed blocked practice) during bilateral training on the BATRAC. The

blocked practice schedule perhaps limited the degree of motor learning that occurred

during the intervention and therefore, limited generalization to motor skills not practiced

directly in the training. Introducing a distributed random practice schedule for the in/anti

phase trials or randomly changing the metronome frequency on trials may have enhanced

the amount of motor learning and thus generalization following this intervention.

Random practice schedules increase the degree of problem solving during execution of

the task by introducing variability in the practice and in turn enhance retention and

generalization ultimately improving the amount of motor learning.1









Providing practice in a more condensed format (2 weeks versus 6 weeks) may have

contributed to the study results. Whitall et al10-12 provided the same training but

distributed the practice over a longer period of time. Currently it is not known if

condensed practice offers differential benefits compared with more distributed practice.

Dettmers21 found that CIMT distributed over 3 weeks with a shorter trial per day ( 3

hours/day) demonstrated improved UE function and quality of life in persons post-stroke.

Page et a122 also showed improved motor skills with a modified form of CIMT provided

in a distributed fashion. However, no study has directly tested a condensed version

against a more distributed version of an identical therapy to determine whether such

practice distribution influences the amount of motor gains experienced in therapy. The

difference in the distribution of practice between this study and Whitall's0o may prove to

be a critical factor in the resultant study outcomes and should be directly investigated in

future research. The distribution and dose of practice to effect a change in motor learning

in individuals post-stroke is clearly not understood.

Several additional aspects of this training may not have been optimal for motor

learning. First, repetitive rhythmic bilateral training may not serve as a robust learning

model since problem solving and the development of a reference of correctness of

movement are not inherently strong or emphasized in the training. The environmental

constraints of the BATRAC (the track and chest restraint) and repetitive nature of the

practice may have resulted in low neural demands and little problem solving. The training

was performed on a track that guided the spatial trajectory of the movements

furthermore; sensory cueing was provided from a metronome, which was self-paced to a

comfortable speed for the participant. This auditory cueing set up a temporal template for









the individuals to match guiding the temporal parameters of the movements. Each end

point stop provided kinesthetic cueing assisting with the timing of the reversal and

indicated the proper extent of movement. Thus, the environment provided specific spatial

and temporal features with predictable consequences, minimizing demands for problem

solving.










(A) (B)

Figure 4-1. BATRAC invariant features, (A) in-phase and (B) anti-phase.

Introducing a margin for potential errors during the intervention might allow for

increased problem solving during task learning which would facilitate the development of

the capability to produce more effective movements and the ability to assess ones own

movement behaviors. Error correction builds movement strategies and a larger repertoire

of available movements to accomplish a task. Schmidt 1 has suggested that these aspects

of motor learning are necessary to retrieve information from long-term memory for

executing a motor skill. Shadmehr23 would argue these components are critical for the

formation of an internal model that would represent the physical dynamics of the limb

and the workspace environment (where the motor skill is performed in relationship to the

body/trunk/ upper extremities). Errors experienced in the training would influence the

performance of the motor skill in an untrained but similar task, contributing to the

performance of the generalization task after intervention. 1









One could argue that learning to coordinate the two upper extremities for in-phase

and anti-phase movement patterns as well as matching the metronome beat was practice

that afforded some degree of problem solving with this intervention. In fact, observing

participants during intervention revealed that indeed there was some difficulty in

coordinating the two limbs to obtain and maintain the temporal phasing of the movement

patterns as well as temporal matching with the metronome. However, temporal phasing

and matching were often accomplished with manual guidance of the therapist which has

been shown to improve performance during the task but not improve motor learning.1' 3

Thus, the degree of problem solving and development of a reference of correctness

during the intervention may not have been sufficient enough for motor learning and

generalization to a novel untrained similar task. If this is true, it is not surprising that little

generalization was found.

Another potential factor affecting the results was that perhaps subjects were not

very engaged in the learning task. The nature of repetitive rhythmic bilateral training on

the BATRAC was similar to an exercise with multiple repetitions versus meaningful

functional task practice. Practicing real life tasks that are motivating to the individual has

been shown to improve acquisition of a motor skill. Wu et al.24demonstrated better

kinematic performance of reaching movements to real objects when compared to

movements without relevant objects in persons post-stroke. Nelson et al.25 studied the

effects of an occupationally embedded exercise on bilaterally assisted supination in

persons post-stroke. Significant results were found for the group receiving real life

(meaningful) practice compared to rote exercise of the same task. Because the BATRAC

lacked meaningful practice, the intervention may have held little motivation for the









participants. Perhaps the results of this intervention would be strengthened if such

bilateral, repetitive exercise were combined with functional task practice that provides

motivation and meaning for the participants for real life skills improving their motor

learning outcome.

Generalization is bolstered when the invariant features are similar between the

training intervention and the novel transfer task. Invariant features of a motor task consist

of the unique traits and rules that are particular to that task. The components chosen as

critical in this study: similar neural demands, joint angles, workspace, angle of visual

gaze, and muscle and joint synergies, may not have been similar enough for

generalization to consistently occur across the selected kinematic outcome measures.

Motor learning, generalization, and retention of a task are strengthened when the training

is varied.1, 3The movement of the upper extremities on the BATRAC did not allow for

diversified movement and therefore there was little room for error detection and the

development of a reference of correction. This intervention involved little to no

interaction with the environment since the objects in the environment did not change

from one attempt to the next. The subject held a handle or was strapped to the handle on

the BATRAC, which offered some degree of weight bearing on the apparatus, and

therefore training motions were closed chain movements. The individual was assisted to

the end point stops if they were unable to complete the task independently. The trunk of

the individual was blocked from forward flexion by a chest plate and proximal arm

motion was encouraged to complete the task. The demands of the task were externally

paced, predictive; the movement was fixed within a particular range and repetitive in

nature requiring minimal monitoring by the participant. Although most subjects









attempted to stay in time with the metronome they were assisted with verbal cues and

occasional manual assistance to coordinate their movements with the beat of the

metronome.

Novel transfer task #1 was chosen because it had many of the characteristics

thought to be important for generalization to occur. The workspace, visual gaze angles to

the target, and joint angles required during the test reaches were identical to the training

intervention utilizing similar muscle and joint synergies to perform the task (novel task

#2 was dissimilar in these parameters). Schmidt1 et al have demonstrated that these

components are necessary for a motor skill to generalize to a novel untrained task.1 While

the lack of generalization may have been due to a lack of learning altogether, the similar

transfer task had other features that were different from the intervention task, which

possibly contributed to the limited generalization.

The transfer task may have required different processing compared to the training

task. Unlike the training intervention there was no track or chest restraint utilized in the

generalization task. The transfer task was a discrete unilateral reaching movement made

in free space with the affected upper extremity to the target and back to the start position.

The only environmental sensory cues were visual in nature: the target and the start

position. No auditory cueing was used other than a verbal cue to begin the movement.

The transfer task required transport of the upper extremity through space against gravity

to the target and back to the start position. One could postulate that both transfer tasks

required greater muscle force to move the limb against gravity then was needed in the

training task although these data were not collected in this study. Certainly more

variations in the movement pattern were available as there were an increased number of









df at upper extremity joints as with the trunk in order to control the transfer task.

Controlling such increased df in the transfer task was quite different than during training

with the BATRAC as an environmental constraint and the chest plate limiting trunk

forward lean. Allowing diversified movement within the execution of the novel task may

have increased the requirements for attentional demands, neural control, problem solving,

and error correction which were not inherent in the intervention. The transfer task

required focused attention on the target, control of the upper extremity through space, and

proprioception (to avoid over or under reaching) unlike the training on the BATRAC

where movements were guided by the track and kinesthic cues were provided by the

distal stops.

Summary

Examination of the invariant features reveals differences in the intervention-

training task and the transfer task that may help to account for the lack of generalization

across the dependent variables. Moving the arm fully through space required controlling

many df which was clearly not something that was trained. Although some of the

environmental constraints were similar: workspace, visual gaze angles; the change from a

closed chain movement in the training intervention to an open chain movement and

increased movement possibilities on the transfer task introduced an increased demand on

the muscular and neural systems as well as the need to problem solve the execution of the

task against gravity.

Identifying the specific features of the repetitive rhythmic bilateral intervention that

will foster generalization to an untrained motor skill in stroke has yet to be determined.

The training may not have provided a strong enough training stimulus or the components

chosen as critical in this study: similar neural demands, joint angles, workspace, angle of









visual gaze, muscle and joint synergies may not have been similar enough for

generalization to consistently occur across the selected kinematic outcome measures. A

lack of complexity in this intervention in regard to decreased demands to problem solve

and lack of development of a reference of correctness may have influenced the amount of

motor learning and further restricted generalization of the intervention to a similar

reaching task.

Limitations to the Study

This study was composed of a heterogeneous group of subjects therefore the

statistical power was influenced by the variance between the subjects (Tables 3-2 and

3-3). A small sample size (n=14) makes it difficult to draw conclusions about the

population in the study and results in a substantial reduction in power. Multiple analyses

on dependent variables were performed but adjusted with a Bonferroni correction

resulting in a more conservative alpha value further reducing the power. Previous

bilateral studies have used small sample sizes and demonstrated significant results on

motor outcome measures but kinematic outcomes have not been reported. Calculating

power at .80 for subsequent studies of this type of bilateral training with the same

dependent variables would require 1050 subjects for significant results. To counter the

violations to the assumption of normality a larger sample size and homogenous sample

would be beneficial in subsequent studies. A homogenous sample in the stroke

population may be difficult to achieve due to the variability of the insult to the CNS.

The inclusion criteria for this study were broad including subjects that had only

palpable extrinsic forearm finger muscle activity and some active shoulder and elbow

motion. Although this intervention was focused on proximal joint and muscle effector

systems and did not train grasp, perhaps the criteria should be modified to include some









degree of finger and hand motion indicating more motor recruitment in the upper

extremity. The inclusion criteria also did not include the ability to move the UE against

gravity a specified degree, which was an inherent part of the transfer tasks and may have

affected the amount of generalization measured at posttest.

Future Studies

Some individuals may have improved with the intervention however delineating

the variables that would discriminate those who might improve from those who might not

improve were limited. Measures to assess multiple factors that potentially could

influence each subjects' baseline and post-testing should be considered: 1) strength in the

upper extremity, 2) coordinative patterns /muscle joint synergies during movement 3)

spasticity, 4) praxis 5) executive functioning, 6) motor learning style (spatial/temporal),

and 7) sensory/proprioceptive status of the affected limb. Collecting the above data of the

participants' capability would further help to assess which subjects were able to benefit

the most from this therapy. Although the side of the lesion was not used as exclusionary

criteria in this study, it has been documented that individuals with a left-sided lesion have

more difficulty with rhythm keeping. 26-29 However, McCombe Waller and

Whitall12demonstrated that persons post-stroke with left-sided lesions improved greater

than persons with right-sided lesions during intervention with the BATRAC. Use of a

metronome in the intervention training sessions may affect the results for particular

subjects by cueing a temporal pace or disadvantageous by creating interference during the

acquisition period of learning where abstract neural signals are transformed into long-

term memory for retrieval at a later time for execution.1' 23 In our study, nine subjects had

left-sided lesions and five had right-sided lesions (Table 2-1). Although no clear pattern

of interference or advantage was evident from the individual data this should be a









consideration in future studies. Assessing the issue of interference of the metronome or

other rhythm keeper used in interventions during the acquisition stage of learning may be

advantageous and revealing when evaluating the results.

Models of the relationship of the dependent variables to each other are not clearly

developed in the field of movement science for the typical population and are evolving

for the stroke population. The numbers of possible kinematic variables and lack of a

model make it difficult to pick just one or two that are expected to change or which

would be the most important for function. The reliability and validity of kinematic

measures in the stroke population has not been established and therefore the stability of

the measures has not been substantiated.30 There was no obvious pattern among

individuals in regard to severity of involvement that predicted which subjects would

improve and on what kinematic outcomes in this study. Several investigators have

theorized that smoothness of the velocity profile demonstrates improved coordination of

the reaching movement with a decrease in stops and starts in the pattern of reaching in

healthy individuals and persons post-stroke.31-34 This supposition would connect the

kinematic variables of PV, HPT, and smoothness metrics, all contributing to the

understanding of coordination and quality of reaching ability in persons post-stroke.30' 35

37 Investigation into the correlation among these kinematic variables related to

performance on reaching tasks might allow selection of the most sensitive measures and

the prediction in their change after intervention.

Conclusions

This study specifically tested generalization of repetitive rhythmic bilateral training

to a similar novel task rather than the overall efficacy or motor learning in upper

extremity function. The kinematic results suggest that at a basic level repetitive rhythmic









bilateral training in and of itself are not enough to effect a change in motor control,

specifically generalization to an untrained novel motor skill across multiple dependent

variables. The novel task may not have held enough of the invariant features of the

training task to truly test generalization of this intervention. The importance of task

analysis of the invariant task features defined for the intervention versus the transfer task

cannot be underestimated. Identification of the critical components of the invariant

features necessary for generalization in the stroke population has yet to be determined.

The adequacy of the intervention in providing an opportunity for motor learning

involving problem solving and the development of a reference of correction without the

connection of real life practice should be scrutinized further. Lastly, the distribution of

practice on a continuous task may affect motor learning and the resultant outcomes and

should be investigated to determine optimal dosage during interventions post-stroke.















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BIOGRAPHICAL SKETCH

Claudia Ann Rutter Senesac, PT, MHS, PCS, has over 27 years of pediatric clinical

experience. She is the owner and administrator of a pediatric physical therapy private

practice since 1984 and is a board certified clinical specialist in pediatrics. She received

her bachelor's degree in physical therapy and master's degree in health science from the

University of Florida. She is graduating with a Doctor of Philosophy in rehabilitation

science with her research interest focused on motor learning and motor control in

neurological and neuromuscular impaired populations: adult individuals who have

suffered a stroke, pediatric individuals that have suffered a SCI, cerebral palsy and

neuromuscular diseases. Investigations have included constraint induced movement

therapy, upper extremity intervention protocols for recovery, and locomotor training in

the pediatric population. She has been an adjunct faculty member of the Physical Therapy

Department at the University of Florida since 1979 and faculty Lecturer since 2003. Her

primary teaching responsibilities in the entry-level doctorate program include Functional

Anatomy I and II and Pediatrics in Physical Therapy.