Neuropsychological aspects of frontal lobe epilepsy. Dominic Upton, Doctor of Philosophy. Institute of Neurology. University of London. LONDON, WON 36G ROCKEFELLER MEOICAL LIBRARY INSTITUTE OF NEUROLOGY THE NATIONAL HOSPITAL QUEEN SQUARE, LONDON, WCIN 33G CLASS ACCN No. d a t e W c ProQuest Number: 10017771 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10017771 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract. This study sought to increase our understanding of the neuropsychological consequences of frontal lobe epilepsy and surgery for this condition. In so doing, some suggestions were made on the role of the frontal lobes, and ways of assessing possible dysfunction in this area. The performance of a large group of subjects with clearly defined frontal lobe epilepsy (n=74), was examined on a comprehensive battery of neuropsychological measures. The performance of this group was compared to a control group of subjects with clearly defined temporal lobe epilepsy (n=57). There were few consistent group differences in test performance. Neither were there any strong relationships between test scores and epilepsy related variables. The frontal lobe group was sub-divided into more discrete regions (dorsolateral, orbital, mesial, motor/premotor, and extensive), and the neuropsychological characteristics associated with dysfunction in these regions was assessed. Although differences between the samples were small, some of the neuropsychological deficits previously associated with these regions were observed. Since a number of measures were used, their validity in assessment of frontal lobe dysfunction was assessed. A composite score of frontal lobe dysfunction was also derived using multivariate analysis. Comparisons revealed that the new composite score can be considered a more sensitive measure in the assessment of frontal lobe epilepsy, than any individual neuropsychological measure investigated. In addition to the group study, four cases were followed up before and at regular intervals after surgery. The results highlighted a number of significant findings, from both a clinical and theoretical perspective. Although the results of the comparisons between frontal and temporal lobe groups, and between different frontal regions. revealed some significant functional differences, these were not consistently demonstrated. The results suggest the necessity to regard these groups collectively, since epileptic activity in any one specific region can cause deficits associated with other areas. Index of contents. Titie Page Title page 1 Abstract 2 Index of contents 4 Index of tables 6 Index of figures 9 Acknowledgements 11 Chapter 1; Overview 12 1.1 Overview 13 Chapter 2: Epilepsy: The condition and its treatment 18 2.1 Definition 19 2.2 Aetiology 20 2.3 Classification 22 2.4 T reatm ent 31 Chapter 3: The frontal lobes: historical perspective 36 3.1 Morphological aspects 37 3.2 Functional aspects 37 Chapter 4: Basic anatomy of the frontal lobes 42 4.1 Gross anatomy of the frontal lobes 43 4.2 Cytoarchitectonie classification 46 4.3 Vascular distribution 48 4.4 Connections with other cortical areas 53 4.5 Conclusion 54 Chapter 5: Development of the frontal lobes 55 5.1 Anatomical development 56 5.2 Cognitive development 56 5.3 Summary and conclusions 63 Chapter 6: Functions of the frontal lobes 64 6.1 Background 65 6.2 Memory 65 6.3 Movement 72 6.4 The frontal lobes and language 76 6.5 Visuo-spatial skills 78 6.6 Executive functions 80 6.7 Mood and personality 86 6.8 Moral judgement 87 6.9 Conclusion 88 Chapter 7: Theories of frontal lobe function 89 7.1 Background 90 7.2 Luria's theory 94 7.3 ShaUice and the Supervisory Attentional 98 System 7.4 Conclusion 107 Index of contents (cont). lit ie Page Chapter 8: Problems with previous research and 109 introduction to current study 8.1 Overview 110 8.2 Terminology 110 8.3 Inappropriate assessments 111 8.4 Inappropriate subject samples 126 8.5 Clinical versus experimental 132 8.6 Neuropsychological studies of frontal lobe 136 epilepsy 8.7 Hypotheses and aims 141 Chapter 9: Method 144 9.1 Introduction 145 9.2 Subjects 147 9.3 Tests 158 9.4 Test construction 173 9.5 Procedure 181 9.6 Statistical analysis 182 9.7 Presentation of results 190 Chapter 10: Results 191 10.1 Results: Hypothesis 1 192 10.2 Results: Hypothesis 2 198 10.3 Results: Hypothesis 3 225 10.4 Results: Hypothesis 4 232 10.5 Results: Hypothesis 5 247 10.6 Results: Hypothesis 6 255 10.7 Results: Hypothesis 7 262 10.8 Results: Hypothesis 8 277 10.9 Results: Hypothesis 9 281 Chapter 11: Discussion of results 309 11.1 Hypothesis 1 and 2 discussion 310 11.2 Hypothesis 3 discussion 334 11.3 Hypothesis 4 discussion 336 11.4 Hypothesis 5 discussion 342 11.5 Hypothesis 6 discussion 345 11.6 Hypothesis 7 discussion 354 11.7 Hypothesis 8 discussion 356 11.8 Hypothesis 9 discussion 358 Chapter 12: General discussion 384 12.1 Introduction 385 12.2 Future research 393 Chapter 13: Summary and Conclusions 395 Chapter 14: References 398 Chapter 15: Appendices 466 Index of tables. Number Title Page 1.1 Conditions associated with frontal lobe dysfunction 14 2.1 Causes of epilepsy presenting at different ages 21 2.2 International classification of epileptic seizures 23 2.3 First and second line anti-epileptic medication 32 2.4 Cognitive consequences of modern anti-epileptic 32 medication 2.5 Most frequent areas of brain areas resected for 34 epilepsy 7.1 Models of frontal lobe functions 91 8.1 Tests thought sensitive to frontal lobe dysfunction 116 9.1 Inclusion criteria for patient sample 148 9.2 Number of subjects in each group 148 9.3 Basic characteristics of subject groups 152 9.4 Basic epilepsy characteristics of the groups 153 9.5 Basic epilepsy variables of the groups 154 9.6 Medication being taken by four groups 154 9.7 Areas of MRI identified frontal lobe damage 156 9.8 Areas of dysfunction according to EEG, MRI, and 156 seizure semiology 9.9 Basic characteristics of normal subject sample 175 9.10 Scores on four versions of cognitive estimates 177 9.11 Correlations between four versions of the cognitive 177 estimation task 9.12 Scores on four parallel versions of DUFFER 177 9.13 Correlations between four versions of the DUFFER 177 9.14 Scores on four parallel versions of cost estimation 179 9.15 Correlations between four versions of the cost 179 estimation task 9.16 Scores on four parallel versions of temporal order 179 task 9.17 Correlations between four versions of the temporal 179 order task 9.18 Scores on four parallel versions of motor sequences 180 task 9.19 Correlations between four versions of the motor 180 sequences task Index of tables (cent). Number Title Page 10.1 Frontal versus temporal lobe groups: background 194 tests 10.2 Frontal versus temporal lobe groups: language and 194 memory tests 10.3 Frontal versus temporal lobe groups: motor skill 195 tests 10.4 Frontal versus temporal lobe groups: executive skills 197 tasks 10.5 CUnical significance of background tests 258 10.6 Clinical significance of language and memory tests 258 10.7 Clinical significance of motor skill tests 259 10.8 Cfinical significance of executive skill tests 260 10.9 Variables entered into logistic regression equation 265 10.10 Initial pass of logistic regression equation 266 10.11 Values of B and Exp(B) for variables entered into 267 logistic regression equation 10.12 Results of logistic regression equation as applied to 269 validation set 10.13 Wilks' lambda and significance of discriminant 272 analysis variables 10.14 Fisher's linear discriminant functions for the four 273 subject groups 10.15 Classification table according to discriminant 275 functions of the training set 10.16 Classification table according to discriminant 276 functions of the validation set 10.17 Wfiks' lambda and significance level for 278 discriminant analysis dependent upon frontal region 10.18 Fisher's linear discriminant functions for frontal 278 regions 10.19 Classification table according to discriminant 279 functions for individual frontal region (training set) 10.20 Classification table according to discriminant 280 functions for individual frontal region (validation set) Index of tables (cont). Number Title Page 10.21 Case MP: Background tests 285 10.22 Case MP: Language and memory tests 286 10.23 Case MP: Motor skills tests 286 10.24 Case MP: Executive skill tests 287 10.25 Case KW: Background tests 291 10.26 Case KW: Language and memory tests 292 10.27 Case KW: Motor skills tests 292 10.28 Case KW: Executive skill tests 293 10.29 Case JS: Background tests 297 10.30 Case JS: Language and memory tests 298 10.31 Case JS: Motor skills tests 298 10.32 Case JS: Executive skill tests 299 10.33 Case SC: Background tests 304 10.34 Case SC: Language and memory tests 305 10.35 Case SC: Motor skills tests 305 10.36 Case SC: Executive skill tests 306 11.1 Background tests: summary 351 11.2 Language and memory tests: summary 351 11.3 Motor skill tests: summary 352 11.4 Executive skill tests: summary 353 Index of figures.