<%BANNER%>

Anterior temporobasal sulcal morphology in temporal lobe epilepsy

Permanent Link: http://ufdc.ufl.edu/UFE0042948/00001

Material Information

Title: Anterior temporobasal sulcal morphology in temporal lobe epilepsy Association with clinical and cognitive variables
Physical Description: 1 online resource (38 p.)
Language: english
Creator: DUNN,CALLIE BECK
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2011

Subjects

Subjects / Keywords: COGNITION -- EPILEPSY -- MEMORY -- MORPHOLOGY -- SULCI
Clinical and Health Psychology -- Dissertations, Academic -- UF
Genre: Psychology thesis, M.S.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Abstract of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Master of Science ANTERIOR TEMPOROBASAL SULCAL MORPHOLOGY IN TEMPORAL LOBE EPILEPSY: ASSOCIATION WITH CLINICAL AND COGNITIVE VARIABLES By Callie J. Beck Dunn May 2011 Chair: Russell Bauer Major: Psychology The anterior temporobasal surface of the brain features the collateral and rhinal sulci. In some brain hemispheres these two sulci are continuous with each other and in other hemispheres they are separated from each other. Previous studies found an increased prevalence of collateral-rhinal connections in individuals with temporal lobe epilepsy (TLE) and Alzheimer?s Disease, leading to the theory that this connection may reflect abnormal brain development and be a risk factor for disease related pathology. Because sulcal morphology is determined very early in development, we predicted that collateral-rhinal connection would be associated with a younger age of epilepsy onset. We also predicted that a collateral-rhinal connection would be associated with the presence of early adverse environmental events (e.g., illness, pre- or peri-natal complications) as well as a family history of neurological illness and epilepsy. Because of the anatomical structures affected by the morphology of the collateral and rhinal sulci, we also predicted that individuals with a collateral-rhinal connection would perform more poorly on a test of item memory but equally as well on a test of spatial memory. Participants were 79 (23 male) individuals with definite or probable TLE. Mean age was 35.84?10.95 years. Scaled scores from Faces Immediate and Delayed and Spatial Span subtests of the Wechsler Memory Scale-III were used. A previously developed and validated rating protocol of sulcal connections was used and interrater reliability was determined to be kappa > .75. Presence of collateral-rhinal connection in the right hemisphere was associated with younger age of onset (99 months vs. 180 months, p<.05). This relationship was not seen in the left hemisphere. There were no significant associations between the presence of a collateral-rhinal connection and presence of early adverse environmental events or presence of a family history of neurological disease or epilepsy. Individuals with a right collateral-rhinal connection performed more poorly on Faces Immediate and Delayed (p<.05). No significant differences were found on Spatial Span performance, and no significant memory-morphology relationships were found for the left hemisphere. A collateral-rhinal connection in the right hemisphere of TLE patients is related to a younger age of onset and is also associated with poorer performance on item memory but not spatial memory. These results lend support to the idea that a collateral-rhinal connection in the right hemisphere may be a sign of abnormal neurodevelopment but further research is needed to clarify this relationship. This also lends support to the distinction between item and spatial memory currently debated in the literature.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by CALLIE BECK DUNN.
Thesis: Thesis (M.S.)--University of Florida, 2011.
Local: Adviser: Bauer, Russell M.
Electronic Access: RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2013-04-30

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2011
System ID: UFE0042948:00001

Permanent Link: http://ufdc.ufl.edu/UFE0042948/00001

Material Information

Title: Anterior temporobasal sulcal morphology in temporal lobe epilepsy Association with clinical and cognitive variables
Physical Description: 1 online resource (38 p.)
Language: english
Creator: DUNN,CALLIE BECK
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2011

Subjects

Subjects / Keywords: COGNITION -- EPILEPSY -- MEMORY -- MORPHOLOGY -- SULCI
Clinical and Health Psychology -- Dissertations, Academic -- UF
Genre: Psychology thesis, M.S.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Abstract of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Master of Science ANTERIOR TEMPOROBASAL SULCAL MORPHOLOGY IN TEMPORAL LOBE EPILEPSY: ASSOCIATION WITH CLINICAL AND COGNITIVE VARIABLES By Callie J. Beck Dunn May 2011 Chair: Russell Bauer Major: Psychology The anterior temporobasal surface of the brain features the collateral and rhinal sulci. In some brain hemispheres these two sulci are continuous with each other and in other hemispheres they are separated from each other. Previous studies found an increased prevalence of collateral-rhinal connections in individuals with temporal lobe epilepsy (TLE) and Alzheimer?s Disease, leading to the theory that this connection may reflect abnormal brain development and be a risk factor for disease related pathology. Because sulcal morphology is determined very early in development, we predicted that collateral-rhinal connection would be associated with a younger age of epilepsy onset. We also predicted that a collateral-rhinal connection would be associated with the presence of early adverse environmental events (e.g., illness, pre- or peri-natal complications) as well as a family history of neurological illness and epilepsy. Because of the anatomical structures affected by the morphology of the collateral and rhinal sulci, we also predicted that individuals with a collateral-rhinal connection would perform more poorly on a test of item memory but equally as well on a test of spatial memory. Participants were 79 (23 male) individuals with definite or probable TLE. Mean age was 35.84?10.95 years. Scaled scores from Faces Immediate and Delayed and Spatial Span subtests of the Wechsler Memory Scale-III were used. A previously developed and validated rating protocol of sulcal connections was used and interrater reliability was determined to be kappa > .75. Presence of collateral-rhinal connection in the right hemisphere was associated with younger age of onset (99 months vs. 180 months, p<.05). This relationship was not seen in the left hemisphere. There were no significant associations between the presence of a collateral-rhinal connection and presence of early adverse environmental events or presence of a family history of neurological disease or epilepsy. Individuals with a right collateral-rhinal connection performed more poorly on Faces Immediate and Delayed (p<.05). No significant differences were found on Spatial Span performance, and no significant memory-morphology relationships were found for the left hemisphere. A collateral-rhinal connection in the right hemisphere of TLE patients is related to a younger age of onset and is also associated with poorer performance on item memory but not spatial memory. These results lend support to the idea that a collateral-rhinal connection in the right hemisphere may be a sign of abnormal neurodevelopment but further research is needed to clarify this relationship. This also lends support to the distinction between item and spatial memory currently debated in the literature.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by CALLIE BECK DUNN.
Thesis: Thesis (M.S.)--University of Florida, 2011.
Local: Adviser: Bauer, Russell M.
Electronic Access: RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2013-04-30

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2011
System ID: UFE0042948:00001


This item has the following downloads:


Full Text

PAGE 1

1 ANTERIOR TEMPOROBASAL SULCAL MORPHOLOGY IN TEMPORAL LOBE EPILEPSY: ASSOCIATION WITH CLINICAL AND COGNITIVE VARIABLES By CALLIE J BECK DUNN A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE UNIVERSITY OF FLORIDA 2011

PAGE 2

2 2011 Callie J. Beck Dunn

PAGE 3

3 To my husband: T he best ally, friend, companion, and teammate

PAGE 4

4 ACKNOWLEDGEMENTS I thank the University of Wisconsin Madison Epilepsy Research Group: Bruce Hermann, Michael Seidenberg, Jana Jones, and Kevin Dabbs for their willingness to collaborate and for their excellent performance within that colla bor ative relationship. I thank Christiana Leonard for her exemplary guidance through the early stages of this thank Gila Reckess for being a mentor to me through this project and teaching m e a great deal about scientific an d critical thinking. I thank Russell Bauer for his leadership and efforts in shaping this study and this student into something better. I thank my parents for meaningfully teaching me the principles of a Gospel centered life and for providing an example of righteous happiness. Finally, I thank my sweet husband for his sacrifices on my behalf and his unwearying support in all of my endeavors.

PAGE 5

5 TABLE OF CONTENTS page ACKNOWLEDGEMENTS ................................ ................................ ............................... 4 LIST OF TABLES ................................ ................................ ................................ ............ 6 LIST OF FIGURES ................................ ................................ ................................ .......... 7 LIST OF ABBREVIATIONS ................................ ................................ ............................. 8 ABSTRACT ................................ ................................ ................................ ..................... 9 CHAPTER 1 INTRODUCTION ................................ ................................ ................................ .... 11 Literature Review ................................ ................................ ................................ .... 11 Previous Research ................................ ................................ ................................ 14 Current Study ................................ ................................ ................................ .......... 15 Rationale and Prediction 1 ................................ ................................ ............... 15 Rationale and Prediction 2 ................................ ................................ ............... 15 Ration ale and Prediction 3 ................................ ................................ ............... 16 Rationale and Prediction 4 ................................ ................................ ............... 16 2 METHODS ................................ ................................ ................................ .............. 19 Subjects ................................ ................................ ................................ .................. 19 Neuropsychological Testi ng ................................ ................................ .................... 20 Image Acquisition ................................ ................................ ................................ ... 21 Automated Sulcal Identification and Labeling ................................ ......................... 21 Rating System ................................ ................................ ................................ ........ 22 3 RESULTS ................................ ................................ ................................ ............... 25 Prediction 1 ................................ ................................ ................................ ............. 25 Prediction 2 ................................ ................................ ................................ ............. 25 Prediction 3 ................................ ................................ ................................ ............. 26 Prediction 4 ................................ ................................ ................................ ............. 26 4 DISCUSSION ................................ ................................ ................................ ......... 31 LIST OF REFERENCES ................................ ................................ ............................... 35 BIOGRAPHICAL SKETCH ................................ ................................ ............................ 38

PAGE 6

6 LIST OF TABLES Table page 2 1 Demographic information ................................ ................................ ................... 24 3 1 Summary of analysis of Wechsler Memory Scale subtest performance. ............ 29

PAGE 7

7 LIST OF FIGURES Figure page 1 1 Image of the basal surface of the left hemisphere as imaged by BrainVISA software ................................ ................................ ................................ ............. 18 2 1 Examples of connection types from Sulcal Classification Rating Protocol: Anterior Temporobasal Sulci. ................................ ................................ ............. 24 3 1 Estimated Marginal Means with Full Scale IQ as a covariate for right hemisphere sulcal morphology. ................................ ................................ .......... 30

PAGE 8

8 LIST OF ABBREVIATION S ANCOVA analysis of covariance ANOVA analysis of variance CS collateral sulcus EEG electroencephalogram FSIQ Full Scale Intelligence Quotient OTS occipitotemporal sulcus RS rhinal sulcus SCRaP:aTB Sulcal Classification Rating Protocol: Anterior Temporobasal Sulci TLE temporal lobe epilepsy WAIS III Wechsler Adult Intelligence Scale Third Edition WMS III Wechsler Memory Scale Third Edition

PAGE 9

9 Abstract of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requir ements for the Degree of Master of Science ANTERIOR TEMPOROBASAL SULCAL MORPHOLOGY IN TEMPORAL LOBE EPILEPSY: ASSOCIATION WITH CLINICAL A ND COGNITIVE VARIABLES By Callie J. Beck Dunn May 2011 Chair: Russel l Bauer Major: Psychology The anterior temporobasal surface of the brain features the collateral and rhinal sulci. In some brain hemispheres these two sulci are continuous with each other and in other hemispheres they are separated from each other. P revious stud ies found an increased prevalence of collateral rhinal connections in individuals with temporal lobe epilepsy (TLE) o the theory that this connection may reflect abnormal brain development and be a risk factor for disease related pathology. Because sulcal morphology is determined very early in development, we predicted that collateral rhinal connection would be associat ed with a younger age of epilepsy onset We also predicted that a collateral rhinal connection would be associated with the presence of early adverse environmental events (e.g., illness, pre or peri natal complications) as well as a family history of neur ological illness and epilepsy. Because of the anatomical structures affected by the morphology of the collateral and rhinal sulci, we also predicted that individuals with a collateral rhinal connection would perform more poorly on a test of item memory but equally as well on a test of spatial memory

PAGE 10

10 Participants were 79 (23 male) individuals with definite or probable TLE. Mean age was 35.8410.95 years. Scaled scores from Faces Immediate and Delayed and Spatial Span subtests of the Wechsler Memory Scale I II were used. A previously developed and validated rating protocol of sulcal connections was used and interrater Presence of collateral rhinal connection in the right hemisphere was associated with younger age of onset (99 months vs. 180 months, p<.05). This relationship was not seen in the left hemisphere. There were no significant associations between the presence of a collateral rhinal connection and presence of early adverse environmental events or presence o f a family history of neurological disease or epilepsy. Individuals with a right collateral rhinal connection performed more poorly on Faces Immediate and Delayed (p<.05). No significant differences were found on Spatial Span performance and no significan t memory morphology relationships were found for the left hemisphere. A collateral rhinal connection in the right hemisphere of TLE patients is re lated to a younger age of onset and is also associated with poorer performance on item memory but not spatial memory. These results lend support to the idea that a collateral rhinal connection in the right hemisphere may be a sign of abnormal neurodevelopment but further research is needed to clarify this relationship. This also lends support to the distinction be tween item and spatial memory currently debated in the literature.

PAGE 11

11 CHAPTER 1 INTRODUCTION Literature Review Sulci are folds in the surface of the human brain which are thought to have evolved as a way to increase the surface area of the brain while staying within the fixed confines of the cranial space (Toro et al., 2008) S ulcal development may begin as early as 14 weeks of gestation (Dubois et al., 2008) and continues through the rest of gestation and into t he first year of life (Dubois et al., 2008; Ono et al., 1990) During this criti cal period of sulcal development, gross morphologic characteristics such as presence or absence of particular sulci, location of sulci, and connections between sulci emerge There is significant variability in gross sulcal morphology both between individu als and between hemispheres of the brain in a single individual (Ono et al., 1990) C hanges in sulcal characteristics may continue throughout the life span (Sowell et al., 2002) and especial ly as individuals age (Kochunov et al., 2005) However, these changes are more likely to affect characteristics such as depth and width of sulci rather than gross morphologic features such as the pattern of connectivity between sulci (Magnotta et al., 1999) The a bsence of an association between age and patterns of sulcal connections in several studies (Novak et al., 2002; Reckess, 2010; Zhan et al., 2009) indicates that there is no reason to believe that patterns of sulcal connections change with age Because there is a critical period of neurodevelopment in utero insults to the developing fetus can affec t the normal development of the bra i n as can genetic factors (Montenegro et al., 2002) One possible sign of abnormal brain development is abnormal patterns of connections between sulci (Kim et al., 2008) A bnormal patterns of

PAGE 12

12 sulcal connection s have been found in a variety of developmental and neuropsychiatric disorders including schizophrenia (Nakamura et al., 2007) Williams Syndrome (Galaburda & Bellugi, 2000) and Alzhe (Zhan et al., 2009) For example, Nakamura and colleagues (200 7) studied the configuration which helps define the boundary of four major orbitofrontal gyri. The configuration was characterized into three types based on the presence or absence of connections among the small sulci that make up of individuals with schizophrenia compared to controls, the distribution of the three types of configurations was opposite the distribution for the controls, such that the configuration type that was least common in controls was most common in patients and was associated with poorer functioning and smaller volume of intra cranial contents. Connections between anterior temporobasal sulci have been studied in (Zhan et al., 2009) as well as in individuals with temporal lobe epilepsy (TLE; Kim et al., 2008; Reckess, 2010) Three sulci are generally referred to by the term include the collateral, rhinal, and occipitotemporal sulci. F igure 1 show s these sulci on the surface of the left hemisphere of the brain as generated by the public d omain software program BrainVISA version 3.2 (Rivire et al., 2002) The position of these sulci on the surface of the medial temporal lobes allow s them to contribute to the size and shape of the hippocampus, parahippocampal gyrus, and perirhinal and entorhinal cortices all of which play a major role in the temporal lobe memory system (Eichenbaum & Lipton, 2008; Eichenbaum et al., 2007) Disease (Zhan et al., 2009) and TLE patients (Kim et al.,

PAGE 13

13 2008) compared to healthy individuals an increased prevalence of connections between the collateral and rhinal sulci have been found Kim and colleagues (2008) created a rating system to classify four different patterns of connections between the three anterior temporobasal sulci. Type 1 consiste d of a single branch, unbroken collateral sulcus connected with the rhinal sulcus anteriorly. Type 2 consisted of the collateral sulcus connected with the occipitotemporal sulcus but separated from the rhinal sulcus. Type 3 consisted of the collateral sulc us separated from the occipitotemporal and rhinal sulci but with the occipitotemporal and rhinal sulci connected. Type 4 consisted of no connections between the collateral, occipitotemporal, and rhinal sulci. After applying this rating system to the magnet ic resonance images of the brains of individuals in their sample, they found an increased prevalence of the Type 1 pattern (collateral rhinal connection) among individuals with TLE ( 77% had the connection in the left hemisphere, 72% in the right) compared to healthy individuals (47% left, 41% right) In discussing these results, Kim, et al. characterized the collateral rhinal a study of cortical complexity measured by the deg ree of gyrification (Luders et al., 2004) Kim, et al. theorized that th e collater al rhinal connection may be an indication of incomplete maturation or disrupted connectivity of the entorhinal and perirhinal cortices that are adjacent to the collateral and rhinal sulci. They postulate d that these mechanisms may directly or indirectly in the development of disease. However, Kim and colleagues did not report investigating any relationships between sulcal connectivity and clinical features of epilepsy, except finding no relationship

PAGE 14

14 between sulcal patt ern type and history of febrile seizures and no association between sulcal pattern type and side of seizure focus in the brain The ir report did not investigate the relationship between pattern type and cognition. Previous R esearch I ntrigued by this stud y Reckess designed her dissertation research as an attempt to replicate and extend these findings (Reckess, 2010) After designing a reliable rating protocol based off of the methodology described by Kim, et al. (2008), she and the current author (CB D ) rated the anterior temporobasal sulcal connection types using brain MR images of 79 individuals with TLE and 70 age matched controls that she obtained through collaboration with the University of Wisconsin Madison Epilepsy Research Group (Hermann et al., 2002a; Hermann et al., 2002b; Hermann et al., 2003; Hermann et al., 2007; Seidenberg et al., 2008; Seidenberg et al., 2007) The results failed to replicate the increased prevalence of the collateral rhinal connection in her sample of TLE patients compared to controls ; the prevalence of collateral rhinal connections in TLE patients (36% left, 46 % right) was not significantly different from the pr evalence among healthy controls (40% left, 41% right). She did however, replicate the absence of a relationship between side of seizure focus in the brain and pattern type. Analysis of the relationship between anterior temporobasal sulcal connections and cognition revealed that a collateral rhinal connection in the right hemisphere was associated with poorer visual delayed and immediate memory performance but not verbal memory performance as measured by index scores from the Wechsler Memory Scale Third Edi tion (Wechsler, 1997a) This finding wa s among the first to suggest a relationship between temporobasal sulcal morphology and memory function.

PAGE 15

15 Current S tudy Using the same s ample and ratings generated as part of the Reckess dissertation, t he purpose of the current study is to investigate the associations between sulcal patterning and clinical variables relevant to the presentation of epilepsy early in the developmental period We were particularly interested in evaluating sulcal relationships with age of epilepsy onset the presence of familial and environmental risk factors for neurologic disease, and cognition in a sample of adults with temporal lobe epilepsy. Rationale an d Prediction 1 S ince abnormal ities in brain develop ment are associated with the develop ment of disease, individuals with abnormal brain development that is present early in life should be more likely to develop disease earlier in the developmental period t han individuals with more normal brain development. Therefore, if the collateral rhinal connection is a sign of subtle, abnormal brain development, as has been proposed (Kim et al., 2008; Zhan et al., 2009) one would expect that disease would present itself earlier in individuals with this type of sulcal connection than in individuals without this type of connection and therefore, presumably, more normal brain development. Therefore, we predicted tha t TLE patients who have a collateral rhinal connection will have a younger age of onset of epilepsy when compared with TLE patients who do not have a collateral rhinal connection. Rationale and Prediction 2 Since sulcal development is influenced by genetic factors, if an individual has a collatera l rhinal connection it is more likely that other members of his or her family also have this connection. Therefore, if the collateral rhinal connection is a sign of subtle, abnormal brain processes that increase the likelihood of developing disease, then a

PAGE 16

16 collateral rhinal connection should be associated with an increased likelihood of a family history of neurologic disease. Rationale and Prediction 3 Since sulcal development is influenced by early environmental factors, adverse events such as complicatio ns with pregnancy or illness or injury in early life could lead to abnormal brain processes that may increase the likelihood of development of disease. I f the collateral rhinal connection is a sign of the presence of subtle, abnormal brain processes, these processes may have begun with an adverse early event. Therefore, we predicted that the collateral rhinal connection would be associated with a history of early adverse environmental events. Rationale and Prediction 4 The study of memory is a large field of research and the understanding of how the brain processes and retrieves information advances. One way of conceptualizing the body of behavioral and anatomic studies (for a review see Eichenbaum & Lipton, 2008; Eichenbaum et al., 2007) is to distinguish between item memory and memory for contextual and spatial detail. Th ese two types of memory involve distinct pathways in the brain with different anatomical substrates Item memory (unimodal representations of remembered items) follows a path way beginning in association areas of the neocortex that process unimodal sensory information. From there, projections enter the perirhinal cortex followed by the lateral entorhinal area before entering the CA3 and CA1 of the hippocampus. In contrast, sp atial or contextual memory (involving complex relationships between items and their context) begins in polymodal association areas of the neocortex before projecti ng to the parahippocampal cortex followed by the medial entorhinal area before entering the C A3

PAGE 17

17 and CA1 of the hippocampus. While there are interconnections between these areas, the pathways remain largely separated until they reach the hippocampus, at which point there are even still patterns of separation between the distinct areas of the hippoc ampus that differentially receive spatial versus item information (Eichenbaum & Lipton, 2008) With this understanding of the org anization of information input i nto the hippoc ampu s, and because the morphology of the collateral and rhinal sulci directly affects the gross morphology of and interconnections between the perirhinal and lateral entorhinal cortices which are implicated in the pathway for the encoding of item information we hypothesized that individuals with a collateral rhinal connection would perform more poorly on a test of item memory than TLE patients without a collateral rhinal connection but would perform equally well on a test of spatial memory.

PAGE 18

18 Figure 1 1. Image of the basal surface of the left hemisphere as imaged by BrainVISA software. The anterior temporobasal surface is outlined in black Within this area, the red sulcus represents the o ccipitotemporal sulcus, the yellow represents the rhinal sulcus, an d the turquoise represents the collateral sulcus.

PAGE 19

19 CHAPTER 2 METHODS Epilepsy pa tient data for this study were collected by colleagues at the University of Wisconsin Madison Epilepsy Research Group in a previous research study that was reviewed and appro ved by the University of Wisconsin School of Medicine and Public Health Human Subjects Research Committee. After the collection of this data, a revision was approved by this same committee to allow sharing of the data with investigators at the University o f Florida, which was also approved by the University of Florida Health Science Center Institutional Review Board (IRB 01) Informed consent was obtained from all subjects. Some descriptions contained in this section are adapted from Hermann, et al. (2007) and Oyebgile, et al. (2004) Subjects This study analyzed data f ro m 79 ( 23 male) subjects who were diagnosed as having complex partial seizures with definite or probable origin in the temporal lobe. The average age of the patient group was 35.8 10.9 years. All patients were between the ages of 14 and 59 years and ha d a Wechsler Adult Intelligence Scale Third Ed ition (WAIS III) Full Scale IQ greater than 69 T able 1 presents other demographic and clinical information. Ep ilepsy subjects were excluded for either of the following criteria : ( a ) presence of MRI abnormaliti es other than atrophy evident on clinical reading or ( b ) presence of neurological disorder other than epilepsy. Confirmation of the hemisphere of origin of the temporal lobe seizures by electroencephalography was obtained in 51 of the subjects with the r esults showing 23 with right temporal lobe origin 19 with left temporal lobe origin and 9 with seizures of bilateral temporal lobe origin. The sample included 27 individuals intending to proceed

PAGE 20

20 to neurosurgery to remove the focus of their seizures with 52 individuals who did not intend to have this procedure. Subjects underwent evaluation of clinical history and characteristics of their epilepsy, and were asked to identify any initial precipitating injuries that occurred prior to the onset of epilepsy. T he y were asked about febrile seizures ; closed head injury with more than 20 minutes of loss of consciousness ; meningitis or encephalitis ; a prenatal insult such as infection with a fever significant bleeding or medical treatment; a perinatal insult such as special procedures needed in the hospital or if the child was not able to go home from the hospital with the mother ; or a non cerebral disease with prolonged hospitalization such as pneumonia or kidney disease Collectively, t hese will be referred to as early adverse environmental events Neuropsychological T esting As part of their epilepsy clinical care at the University of Wisconsin, each subject completed a comprehensive neuropsychological assessment. Two subtests of the Wechsler Memory Scale Thir d Edition (WMS III) were chosen as adequately representative of item (Faces Immediate and Delayed) and spatial (Spatial Span) memory The Faces subtest consists of the presentation of 24 pictures of faces followed by an immediate test of yes no recognitio n in which the 24 targets are intermixed with 24 distracters The delayed recognition trial is administered 25 to 35 minutes later and involves the original 24 faces intermixed with 24 new distracters The Spatial S pan subtest is a variation on the Corsi Blocks test (Milner, 1971) and consists of a fixed array of blocks. The subject is asked to touch the blocks in the same order as demonstrated by the examiner. As with Digit Span, each successive pair of trials increases in length. The test continues until the examinee fails two trials at a given

PAGE 21

21 length Scaled scores of the performance on these subtests were used in analyses (Wechsler, 1997b) Image A cquisition Brain scans were obtained on a 1.5 Tesla GE Signa Magnetic Resonance scanner. Scan parameters are described in Hermann, et al. (2007) Sequences that were acquired for each subject included (1) T1 weighted, three dimensional spoiled gradient recalled (2) Proton Density, and (3) T2 weighted images. Images that were deemed usabl e by Hermann and colleagues were de identified, copied to a data storage devi c e, and mailed to the University of Florida. Automated Sulcal Identification and L abeling Processing of the images acquired from the University of Wisconsin was conducted at the U niversity of Florida as part of a concurrent doctoral dissertation and is described elsewhere (Reckess, 2010) The MRIs were processed using BrainVISA version 3.2 a public domain software platform for the analysis of brain images developed by Rivi re and colleagues (Rivire et al., 2002) at the Laboratoire de Neuroimagerie Assiste par Ordinateur BrainVISA contains a toolbox that automatically recognizes and labels cortical sulci by employing a co ngregation of neural networks that are trained in sulcal identification and labeling based on maximizing similarity of the processed image to catalogued sulcal features and relations. The resulting image is a three dimensional representation of the surface of the brain with the sulc i f illed in u sing a color designated to identify a particular sulcus in a particular region. However, this color scheme is not always accurate, as has been described elsewhere (Reckess, 2010) and requires human raters t o validate and check the labeling

PAGE 22

22 Rating S ystem The rating system used in this study was developed as part of the doctoral diss ertation of Gila Reckess at the University of Florida (Reckess, 2010) Reckess created a manualized protocol to classify patterns of connectivity among the collateral, occipitotempora l, and rhinal sulci. This protocol is referred to as the Sulcal Classification Rating Protocol: Anterior Temporobasal Sulci (SCRaP:aTB) and is based on the rating system described by Kim, et al. (2008) While Reckess only partially replicated the findings presented by Kim, et al., she used sound methodology in creating the protocol, including reaching an inter r > .75 Also the protocol delivered consistent ratings across two separate control groups with different collection sites, different average age of the sample, different sex proportion s and different image acquisition parameters. This between group consistency offers evidence f or the exter nal validity of SCRaP:aTB Therefore, while it is possible that the protocol may not be capturing the exact same nuances contained within the Kim, et al. system, it is an equally valid and accurate method of classification, a fact that justifies its use in this study. Based on the methodology an d statistical reliability of SCRaP:aTB we can conclude that the ratings Reckess developed are detecting reliable distinctions in the patterns of connectivity amon g the three major anterior temporobasal sulci. The rating process for the classification of the pattern type in this study involved independent raters (CB D and GZR inter ) who were blind to patient demographics and diagnosis T he raters evaluated the entire s ample of brains using the SCRaP:aTB After this was completed, a series of consensus conferences were held to discuss and resolve any discrepancies that would affect the pattern classification for each hemisphere of each bra in. Figure 2 shows examples of each of

PAGE 23

23 the four pa ttern types distinguished by SCRaP:aTB It should be noted that Type 3 did not occur in the right hemisphere of any subject in th e sample and occurred in the left hemisphere in only one individual. Because of this, the one instance of Type 3 was coded in analyses to be in the Type 4 group. Therefore subsequent analyses refer to only three connection types ( collateral rhinal, collateral occipitotemporal, no connections ).

PAGE 24

24 Table 2 1. Demographic i nformation Age 35.8 10.9 years Education 12.9 2.1 years IQ 92.6 16.3 Duration of epilepsy 2 2. 3 1 1 .6 years Figure 2 1 Examples of connection types from Sulcal Classification Rating Protocol: Anterior Temporobasal Sulci Type 1 shows a connection between the yellow rhinal sulcus and the turquoise collateral sulcus in the absence of a connection with the red occipitotemporal sulcus. Type 2 shows a connection with the orange collateral sulcus and the red o ccipitotemporal s ulcus in the absence of a connection with the turquoise rhinal sulcus. Type 3 shows a connection between the yellow rhinal sulcus and the red occipitotemporal sulcus in the absence of a connection with the turquoise collateral sulcus. Type 4 shows an absen ce of connection between any of the three anterior temporobasal sulci.

PAGE 25

25 CHAPTER 3 RESULTS Prediction 1 Groups were divided by presence versus absence of a collateral rhinal connection. Due to (1) a positively skewed and leptokurtic distribution of age of onset for both right hemisphere groups and for the individuals without a collateral rhinal connection in the left hemisphere and (2) a platykurtic distribution in individuals with a collateral rhinal connection in the left hemisphere nonparametric rank su m analysis was used. Interrater reliability for left hemisphere ratings was .76 while kappa was .68 for right hemisphere ratings. There were 28 (36%) individuals with a collateral rhinal connection in the left hemi sphere versus 50 without and 3 6 (46%) with this connection in the right hemisphere versus 43 without. There were no significant differences in education, F ull S cale IQ (Wechsler Adult Intelligence Scale III) or duration of epilepsy between those with and without a left or right hemisphere col lateral rhinal connection (all p > .05). However, individuals with a collateral rhinal connection in their right hemisphere had a significantly older age (38.5 + 9. 5 years) than those without a connection (32.6 + 11.8 years) in the right hemisphere [ t (77 ) = 2.45 p = 02 ] Results indicated a significantly younger median age of epilepsy onset for individuals with a collateral rhinal connection in the right hemisphere (99 months; 8 years 3 months) compared to those without (180 months; 15 years), ( Z = 1.800 p 2 = .042). This relationship was not significant in the left hemisphere ( p = .190). Prediction 2 To test the prediction that presence of a collateral rhinal connection would be associated with a family history of neurologic disease, Pearson c hi squares were used

PAGE 26

26 A chi square of the presence/absence of right hemisphere collateral rhinal connection versus presence/absence of a family history of neurologic disorders revealed a chi square of .521 with a 1 p = .319. A chi square of the presence/absence of left hemisphere collateral rhinal connection versus presence/absence of a family history of neurologic disorders revealed a chi square of .671 with a 1 p = .287. The analysis was then restricted to a family history of epilepsy. A chi square divided by presence/absence of right hemisphere collateral rhinal connection versus 1 square of left hemisphere collateral rhinal sided Prediction 3 Chi square was also used to test the prediction that collateral rhinal connection wou ld be associated with the presence of early adverse environmental events. A chi square analysis of presence/absence of right hemisphere collateral rhinal connection versus presence/absence of an adverse environmental event revealed no significance 2 = 6 91 1 p = .2 78 ). A chi square of left hemisphere collateral rhinal connection and adverse environmental events 2 = 1 479 1 p = .167 ). Prediction 4 To test the prediction that individuals with a collateral rhinal connection would perform more poorly on a test of item memory than individuals without a coll ateral rhinal connection but would perform equally as well on a test of spatial memory separate

PAGE 27

27 ANCOVAs were conducted for e ach of three scores (Faces Immediate scaled score, Faces Delayed scaled score, and Spatial Span scaled s core) in each of the two hemispheres (6 total analyses). The groups were divided by connection type such that there were three groups ( collateral rhinal connection, collateral occipitotemporal connection, no connections between all three anterior temporobasal sulci). Full scale IQ from the WAIS III (FSIQ) was used as a covariate based on significant moderate ly sized P earson correlations between FSIQ and all three scores used ( r FSIQ, Faces Imm. = .402, r FSIQ, Faces Delay = .349, r FSIQ, Spatial Span = .690, all p < .001) Lateralization of seizures was also considered as a possible covariate. 28 individuals did not have EEG lateralization data and were excluded from these preliminary analyses. One way ANOVAs of lateralization of seizure effects on performance on the Faces Immediate and Delayed subtests faile d to reach significance. Lateralization was therefore not included in subsequent Faces analyses and data from all 79 individuals were used. However, for performance on the Spatial Span subtest, the effect of lateralization of seizures was significant [F(2, 48)=3.285, p = .046] Significant gr oup differences were found such that individuals with right hemisphere seizures performed significantly better than individuals with seizures originating from both hemispheres (Bonferroni corrected p = .041) Due to the significant association between Spatial Span performance and lateralization of seizures, two analyses in addition to the ones described above were planned involving the Sp atial Span performance variable: 1. An ANCOVA using connection type in the right hem isphere as the independent variable and FSIQ and lateralization of seizures as the covariate s with Spatial Span performance as the dependent variable. 2. An ANCOVA using connection type in the

PAGE 28

28 left hemisphere as the independent variable and FSIQ and latera lization of seizures as the covariate s with Spatial Span performance as the dependent variable. These two analyses would exclude data from 28 individuals who did not have EEG lateralization data. Helmert contrasts were planned for all analyses. In these contrasts individuals with a collateral rhinal connection would be compared to all other subjects, followed by individuals with a collateral occipitotemporal connection compared to individuals with no connections between the th ree anterior temporobasal sul ci. Results revealed no significant differences on any o f the three measures for groups based on left hemisphere sulcal connectivity. However, for groups based on right hemisphere connectivity, significant differences were found [F(2,79)=4.110, p = .02) such that on Faces Immediate and Faces Delay individuals with a collateral rhinal connection performed significantly lower than other individuals No significant differences were found between the collateral occipitotemporal connection group and the no connection group. No significant differences were found on Spatial Span scores for groups based on sulcal morphology This was also true based on the results of the analyses with the addition of the lateralization of seizures variable. Table 2 contains a summary of these analyses, while Figure 3 depicts the estimated marginal means for the groups based on right hemisphere sulcal connectivity using the analyses that included the entire sample.

PAGE 29

29 Table 3 1. Summary of analysis of Wechsler Memory Scale subtest performance. WMS III Subtest Overall ANCOVA CS RS connected vs. others CS OTS connected vs. no connection Partial Eta Squared Right Hemisphere Faces Imm. *F(2,75)=3.138, p =.049 p = .037 p = .359 .077 Faces Delay *F(2,75)=4.110, p = .02 ** p =.006 p = .99 .099 Spatial Span F(2,75)=0.178, p = .838 p = .774 p = .574 Spatial Span+ F(2,41)=0.476, p = .625 p = .443 p = .486 Left Hemisphere Faces Imm. F(2,74)=0.199, p = .82 p = .604 p = .78 Faces Delay F(2,74)=1.738, p = .183 p = .075 p = .476 Spatial Span F(2,74)=0.687, p =.501 p = .242 p = .913 Spatial Span+ F(2,40)=1.950, p = .156 p = .064 p =.323 Summary of analysis of Wechsler Memory Scale subtest performance divided by hemisphere and subtest. The third column contains the F statistic of the main effect of sulcal morphology from the analysis of covariance and its significance. The fourth column co ntains the significance of the Helmert contrast comparing the individuals with a collateral rhinal connection to individuals with any other connection type. The fifth column contains the significance of the Helmert contrast comparing individuals with a col lateral occipitotemporal connection to individuals with no connections between the three anterior temporobasal sulci. WMS III: Wechsler Memory Scale Third Edition ANCOVA: Analysis of covariance CS: Collateral sulcus RS: Rhinal sulcus OTS: Occipitotemporal sulcus +: These analyses included lateralization of seizure information and used a smaller sample. *: p < .05 **: p < .01

PAGE 30

30 Figure 3 1. Estimated Marginal Means with Full Scale IQ as a covariate for right hemisphere sulcal morphology. CS: Collateral sulc us RS: Rhinal sulcus OTS: Occipitotemporal sulcus : p < .05 for significant difference between collateral rhinal connection performance compared to other two groups combined. **: p < .01 for significant difference between collateral rhinal connection per formance compared to other two groups combined.

PAGE 31

31 CHAPTER 4 DISCUSSION The resul ts of the above analyses lead to several findings : a collateral rhinal connection in the right hemisphere of temporal lobe epilepsy p atients was related to a younger age of disease onset ; a collateral rhinal connection in temporal lobe epilepsy patients wa s not significantly associated with a family history of neurologic disease or with a family history of epilepsy ; a collateral rhinal connection wa s not sig nificantly associated with a history of an ea rly adverse environmental event ; and a collateral rhinal connection in the r ight hemisphere was related to poorer performance on a test of item memory but not to performance on a test of spatial memory. The y ounger age of epilepsy onset associated with the collateral rhinal connection in the right hemisphere supports the theory that presence of a collateral rhinal connection may be a neurodevelopmental risk factor for the development of neurological disease. The balance between genetic and environmental factors in the development of disease was not elucidated in this study as there was no association between the possible indicator of abnormal neurodevelopment and a family history of disease or the presence of adve rse environmental factors. The lack of significant association s may have been due to the reliance on retrospective reports of pre and perinatal factors by the epilepsy patients without outside validation of these reports directly from the medical record It is also likely that an interaction between genetic, epigenetic, and environmental factors is the cause of the development of disease, so it is not surprising that simple associations were not found. D ue to the retrospective nature of this study it i s impossible to determine a cause and effect r elationship between gross sulcal morphology and the onset of epilepsy It

PAGE 32

3 2 may be that a collateral rhinal connection conveys vulnerability to the development of the disease as Kim et al suggested. However, it is also possible that the connection developed as a result of disease processes or some other factor early in development. A prospective study or a sample with pre and post onset of epilepsy brain images would be necessary to explore the causality of t his relationship. The finding that a collateral rhinal connection in the right hemisphere was related to poorer performance on a test of item memory but not spatial memory is consistent with recent findings from anatomical and neuroimaging studies, and le nds support to the idea that distinctions between item memory and spatial memory are useful (Eichenbaum & Lipton, 2008) The position of the collateral and rhinal sulc i adjacent to the perirhinal and lateral entorhinal cortices allows their morphology to affect the morphology of these cortical areas and their interconnections. The perirhinal and lateral entorhinal cortices have been implicated in the processing of unimo dal representations of remembered items (Suzuki & Eichenbaum, 2000) as well as famili arity or recognition of stimuli without recollection of stimulus associations (Eichenbaum et al., 2007) The type of stimuli presented in the Faces subtest of the WMS III (Wechsler, 1997b) is unimodal (visual) and stimuli have no identifying information or associations other than any memory strategies that the patient may use to remember the faces. The contextual pathway processes information involving co mplex relationships between items and their context and utilizes projections to the parahippocampal cortex followed by the medial entorhinal area before entering the hippocampus (Eichenbau m & Lipton, 2008) These areas are further from the location where the connection between the collateral and rhinal sulci would be taking place than the entorhinal and perirhinal cortices are T he

PAGE 33

33 poorer performance of TLE patients with a collateral rhi nal connection in the right hemisphere indicate s that this connection in the right hemisphere may adversely affect the functioning of the item memory pathway in the medial temporal lobe system while not significantly affecting the contextual memory pathway compared to TLE patients without a collateral rhinal connection. However, t he Faces and Spatial Span subtests of the WMS III are certainly not proc ess pure measures of item and spatial memory It is possible that other cognitive processes that are measured by these tasks could be confounded in this study. Also considering the small effect sizes for the significant ANOVAs involving Faces Immediate 2 = .099) as well as the standard error of measurement associated with these subtests (Faces Immediate = 1.44 scaled score; Faces Delay = 1.43 scaled score; Wechsler, 1997b) it is unclear if the statistically significant differences found in this study have clinical significance. Future directions of study may include usin g experimental measures or more process pure tasks to test performance of item memory versus spatial memory in groups based on sulcal connection patterns in TLE patients or other patient populations and controls. Extending the SCRaP:aTB rating system into other patient populations would provide further validation of this protocol and allow for comparisons of anterior temporobasal sulcal patterns to be made across patient populations using a standardized protocol. This study explored gross sulcal morphology clinical variables and neuropsychological performance in a large sample of temporal lobe epilepsy patients. Morphological ratings were based on a reliable protocol. Younger age of onset of

PAGE 34

34 epilepsy and poorer performance on a test of item memory were ass ociated with a collateral rhinal connection in the right hemisphere of temporal lobe epilepsy patients. These findings support the idea that a collateral rhinal connection may be an indication of abnormal neurodevelopment that adversely affects the item me mory pathway of the medial temporal lobe memory system.

PAGE 35

35 LIST OF REFERENCES Dubois J, Benders M, Cachia A, Lazeyras F, Ha Vinh Leuchter R, Sizonenko SV, Borradori Tolsa C, Mangin JF, Huppi PS. (2008) Mapping the early cortical folding process in the preterm newborn brain. Cereb Cortex 18:1444 1454. Eichenbaum H, Lipton PA. (2008) Towards a functional organization of the medial temporal lobe memory system: role of the parahippocampal and medial entorhinal cortical areas. Hippocampus 18:1314 1324. Eichenbaum H, Yonelinas AP, Ranganath C. (2007) The medial temporal lobe and recognit ion memory. Annu Rev Neurosci 30:123 152. Galaburda AM, Bellugi U. (2000) V. Multi level analysis of cortical neuroanatomy in Williams syndrome. J Cogn Neurosci 12 Suppl 1:74 88. Hermann B, Seidenberg M, Bell B. (2002a) The neurodevelopmental impact of c hildhood onset temporal lobe epilepsy on brain structure and function and the risk of progressive cognitive effects. Prog Brain Res 135:429 438. Hermann B, Seidenberg M, Bell B, Rutecki P, Sheth R, Ruggles K, Wendt G, O'Leary D, Magnotta V. (2002b) The ne urodevelopmental impact of childhood onset temporal lobe epilepsy on brain structure and function. Epilepsia 43:1062 1071. Hermann B, Seidenberg M, Bell B, Rutecki P, Sheth RD, Wendt G, O'Leary D, Magnotta V. (2003) Extratemporal quantitative MR volumetri cs and neuropsychological status in temporal lobe epilepsy. J Int Neuropsychol Soc 9:353 362. Hermann B, Seidenberg M, Lee EJ, Chan F, Rutecki P. (2007) Cognitive phenotypes in temporal lobe epilepsy. J Int Neuropsychol Soc 13:12 20. Kim H, Bernasconi N, Bernhardt B, Colliot O, Bernasconi A. (2008) Basal temporal sulcal morphology in healthy controls and patients with temporal lobe epilepsy. Neurology 70:2159 2165. Kochunov P, Mangin JF, Coyle T, Lancaster J, Thompson P, Riviere D, Cointepas Y, Regis J, Schlosser A, Royall DR, Zilles K, Mazziotta J, Toga A, Fox PT. (2005) Age related morphology trends of cortical sulci. Hum Brain Mapp 26:210 220. Luders E, Narr KL, Thompson PM, Rex DE, Jancke L, Steinmetz H, Toga AW. (2004) Gender differences in cortical complexity. Nat Neurosci 7:799 800. Magnotta VA, Andreasen NC, Schultz SK, Harris G, Cizadlo T, Heckel D, Nopoulos P, Flaum M. (1999) Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging. Cereb Cortex 9:151 1 60. Milner B. (1971) Interhemispheric differences in the localization of psychological processes in man. Br Med Bull 27:272 277.

PAGE 36

36 Montenegro MA, Guerreiro MM, Lopes Cendes I, Guerreiro CA, Cendes F. (2002) Interrelationship of genetics and prenatal injury in the genesis of malformations of cortical development. Arch Neurol 59:1147 1153. Nakamura M, Nestor PG, McCarley RW, Levitt JJ, Hsu L, Kawashima T, Niznikiewicz M, Shenton ME. (2007) Altered orbitofrontal sulcogyral pattern in schizophrenia. Brain 130:693 707. Novak K, Czech T, Prayer D, Dietrich W, Serles W, Lehr S, Baumgartner C. (2002) Individual variations in the sulcal anatomy of the basal temporal lobe and its relevance for epilepsy surgery: an anatomical study performed using magnetic resonance imaging. J Neurosurg 96:464 473. Ono M, Kubick S, Abernathey C. (1990) Atlas of the Cerebral Sulci Thieme Medical Publishers, New York. Oyegbile T, Hansen R, Magnotta V, O'Leary D, Bell B, Seidenberg M, Hermann BP. (2004) Quantitative measurement of cortical surf ace features in localization related temporal lobe epilepsy. Neuropsychology 18:729 737. Reckess GZ. (2010) Temporobasal sulcal morphology: Configural patterns and neurocognitive relevance in healthy adults and patients with Temporal Lobe Epilepsy. Depar tment of Clinical and Health Psychology University of Florida, Gainesville, Florida, p. 94. Rivire D, Mangin JF, Papadopoulos Orfanos D, Martinez JM, Frouin V, Regis J. (2002) Automatic recognition of cortical sulci of the human brain using a congregatio n of neural networks. Med Image Anal 6:77 92. Seidenberg M, Hermann B, Pulsipher D, Morton J, Parrish J, Geary E, Guidotti L. (2008) Thalamic atrophy and cognition in unilateral temporal lobe epilepsy. J Int Neuropsychol Soc 14:384 393. Seidenberg M, Pul sipher DT, Hermann B. (2007) Cognitive progression in epilepsy. Neuropsychol Rev 17:445 454. Sowell ER, Thompson PM, Rex D, Kornsand D, Tessner KD, Jernigan TL, Toga AW. (2002) Mapping sulcal pattern asymmetry and local cortical surface gray matter distri bution in vivo: maturation in perisylvian cortices. Cereb Cortex 12:17 26. Suzuki WA, Eichenbaum H. (2000) The neurophysiology of memory. Ann N Y Acad Sci 911:175 191. Toro R, Perron M, Pike B, Richer L, Veillette S, Pausova Z, Paus T. (2008) Brain size a nd folding of the human cerebral cortex. Cereb Cortex 18:2352 2357.

PAGE 37

37 Wechsler D. (1997a) Wechsler Memory Scale. Psychological Corp, San Antonio, Texas. Wechsler D. (1997b) Wechsler Memory Scale -Third Edition. Administration and scoring manual The Psycho logical Corporation, San Antonio, TX. Zhan J, Brys M, Glodzik L, Tsui W, Javier E, Wegiel J, Kuchna I, Pirraglia E, Li Y, Mosconi L, Saint Louis LA, Switalski R, De Santi S, Kim BC, Wisniewski T, Reisberg B, Bobinski M, de Leon MJ. (2009) An entorhinal co rtex sulcal pattern is associated with Alzheimer's disease. Hum Brain Mapp 30:874 882.

PAGE 38

38 BIOGRAPHICAL SKETCH Callie Jo Beck Dunn was born in 1985 in Burley, Idaho. The fifth of six children, Callie grew up in this quiet town until she graduated from Burley High School in May 2003 as one of its valedictorians. She then continued her education, enrolling in Brigham Young University (BYU) in June of 2003. As a freshman she began research with Dr. Ramona Hopkins at BYU and gained valuable experience in the utility of neuropsychology in a hospital setting. After putting her academic development on hold for 18 months to serve a religious mission to New Caledonia with the Church of Jesus Christ of Latter day Saints, Callie graduated summa cum laude from BYU with a B.S. in p sychology in August 2009 as the department valedictorian. She then began her graduate studies in the Department of Clinical and Health Psychology at the University of Florida in August 2009 working under the mentorship of Dr. Russell Bauer. In November of 2009, she met her future husband, Christopher Dunn. C allie and Chris were married two week s after the defense of this thesis