Extrahippocampal gray matter atrophy and memory impairment in patients with medial temporal lobe epilepsy

Memory impairment observed in patients with medial temporal lobe epilepsy (MTLE) is classically attributed to hippocampal atrophy. The contribution of extrahippocampal structures in shaping memory impairment in patients with MTLE is not yet completely understood, even though atrophy in MTLE extends beyond the hippocampus. We aimed to evaluate the neuropsychological profile of patients with MTLE focusing on memory, and to investigate whether gray matter concentration (GMC) distribution within and outside the medial portion of the temporal lobes would be associated with their neuropsychological performance. We performed a voxel based morphometry study of 36 consecutive patients with MTLE and unilateral hippocampal atrophy. We observed a significant simple regression between general and verbal memory performance based on Wechsler Memory Scale—Revised and the GMC of medial temporal and extratemporal structures in patients with left MTLE. We also performed a “regions of interest analysis” of the medial temporal lobe, and we observed that the GMC of the hippocampus, entorhinal, and perirhinal cortices were consistently associated with general and verbal memory performance in patients with MTLE. We also observed that the GMC of the cingulate and orbito‐frontal cortex are independently associated with verbal and general memory performances. Our results suggest that general and verbal memory impairments in patients with left MTLE are associated with atrophy of the hippocampus, the entorhinal, and the perirhinal cortex. We also suggest that atrophy and dysfunction of limbic and frontal structures such as the cingulate and the orbito‐frontal cortex contribute to memory impairment in MTLE. Hum Brain Mapp 2007. © 2007 Wiley‐Liss, Inc.

[1]  E Kobayashi,et al.  Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy , 2003, Journal of neurology, neurosurgery, and psychiatry.

[2]  U. Wieshmann,et al.  Eugene Jamot (1879–1937) , 2002, Journal of neurology, neurosurgery, and psychiatry.

[3]  Eliane Kobayashi,et al.  Magnetic resonance imaging abnormalities in familial temporal lobe epilepsy with auditory auras. , 2003, Archives of neurology.

[4]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[5]  B. N'Kaoua,et al.  Effect of age of onset of temporal lobe epilepsy on the severity and the nature of preoperative memory deficits , 2002, Neuropsychologia.

[6]  D. Amaral,et al.  Lesions of the perirhinal and parahippocampal cortices in the monkey produce long-lasting memory impairment in the visual and tactual modalities , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  T. Kurashige,et al.  Proposal for Revised Classification of Epilepsies and Epileptic Syndromes , 1989, No to hattatsu = Brain and development.

[8]  K. Kennedy,et al.  Age Effects on Trail Making Test Performance , 1981, Perceptual and motor skills.

[9]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[10]  David Gaffan Widespread Cortical Networks Underlie Memory and Attention , 2005, Science.

[11]  J Overweg,et al.  Effect of epilepsy, seizures and epileptiform EEG discharges on cognitive function , 1996, Acta neurologica Scandinavica.

[12]  H E ROSVOLD,et al.  A comparison of the psychological test performance of atients with focal and nonfocal epilepsy. , 1960, Experimental neurology.

[13]  J. Hogg Magnetic resonance imaging. , 1994, Journal of the Royal Naval Medical Service.

[14]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[15]  Mark S. Seidenberg,et al.  Effects of Age of Onset of Partial and Generalized Seizures on Neuropsychological Performance in Children , 1983, The Journal of nervous and mental disease.

[16]  H. Eichenbaum A cortical–hippocampal system for declarative memory , 2000, Nature Reviews Neuroscience.

[17]  J. Engel,et al.  The timing of surgical intervention for mesial temporal lobe epilepsy: a plan for a randomized clinical trial. , 1999, Archives of neurology.

[18]  D. Gaffan,et al.  Unilateral lesions of the cholinergic basal forebrain and fornix in one hemisphere and inferior temporal cortex in the opposite hemisphere produce severe learning impairments in rhesus monkeys. , 2002, Cerebral cortex.

[19]  Pablo A. Rio,et al.  Voxel-based morphometry reveals gray matter network atrophy in refractory medial temporal lobe epilepsy. , 2004, Archives of neurology.

[20]  David C. Van Essen,et al.  Application of Information Technology: An Integrated Software Suite for Surface-based Analyses of Cerebral Cortex , 2001, J. Am. Medical Informatics Assoc..

[21]  P Alvarez,et al.  Memory consolidation and the medial temporal lobe: a simple network model. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[23]  F. Cendes,et al.  Differences in memory performance and other clinical characteristics in patients with mesial temporal lobe epilepsy with and without hippocampal atrophy , 2004, Epilepsy & Behavior.

[24]  R. Haaxma,et al.  The mental status examination in neurology. F. A. Davis Company (1977), 182 pp., Price Fl. 24,25 , 1978 .

[25]  Amanda Parker,et al.  Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions , 1998, Neuropsychologia.

[26]  Bill Faw Pre-frontal executive committee for perception, working memory, attention, long-term memory, motor control, and thinking: A tutorial review , 2003, Consciousness and Cognition.

[27]  Chris Rorden,et al.  Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy , 2006, Epilepsy & Behavior.

[28]  L. Squire,et al.  The medial temporal lobe memory system , 1991, Science.

[29]  L. Squire,et al.  Structure and function of declarative and nondeclarative memory systems. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  P. Dreyfus A TEXTBOOK OF EPILEPSY. , 1978 .

[31]  F Andermann,et al.  Morphometric MRI Analysis of the Parahippocampal Region in Temporal Lobe Epilepsy , 2000, Annals of the New York Academy of Sciences.

[32]  Mark S. Seidenberg,et al.  Effects of Age of Onset of Tonic‐Clonic Seizures on Neuropsychological Performance in Children , 1981, Epilepsia.

[33]  L. Squire Memory systems of the brain: A brief history and current perspective , 2004, Neurobiology of Learning and Memory.

[34]  Alcino J. Silva,et al.  New Circuits for Old Memories The Role of the Neocortex in Consolidation , 2004, Neuron.

[35]  Michael Burke,et al.  Content-specific activation during associative long-term memory retrieval , 2005, NeuroImage.

[36]  H. Jokeit,et al.  Long term effects of refractory temporal lobe epilepsy on cognitive abilities: a cross sectional study , 1999, Journal of neurology, neurosurgery, and psychiatry.

[37]  B. Milner,et al.  Psychological defects produced by temporal lobe excision. , 1958, Research publications - Association for Research in Nervous and Mental Disease.

[38]  W. van Paesschen,et al.  Hippocampal cell loss and gliosis: relationship to preoperative and postoperative memory function. , 1998, Neuropsychiatry, neuropsychology, and behavioral neurology.

[39]  Seth J. Ramus,et al.  Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system , 1994, Hippocampus.

[40]  Neil Roberts,et al.  Voxel-Based Morphometric Comparison of Hippocampal and Extrahippocampal Abnormalities in Patients with Left and Right Hippocampal Atrophy , 2002, NeuroImage.

[41]  H. Hunter The treatment of epilepsy. , 1948 .

[42]  David Gaffan,et al.  Against memory systems. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[43]  Silke Lux,et al.  Chronic epilepsy and cognition: A longitudinal study in temporal lobe epilepsy , 2003, Annals of neurology.

[44]  D. Gaffan,et al.  Dense amnesia in the monkey after transection of fornix, amygdala and anterior temporal stem , 2001, Neuropsychologia.

[45]  R. Mattson,et al.  Selective memory improvement and impairment in temporal lobectomy for epilepsy , 1984, Annals of neurology.

[46]  T L Babb,et al.  Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. , 1993, Archives of neurology.

[47]  D. Arnold,et al.  Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region. , 2003, Brain : a journal of neurology.

[48]  Aubrey J. Yates,et al.  INTELLECTUAL CHANGES FOLLOWING TEMPORAL LOBECTOMY FOR PSYCHOMOTOR EPILEPSY , 1955, Journal of neurology, neurosurgery, and psychiatry.

[49]  T. Bussey,et al.  Perceptual–mnemonic functions of the perirhinal cortex , 1999, Trends in Cognitive Sciences.

[50]  E. Kaplan,et al.  The Boston naming test , 2001 .

[51]  Richard H. Mattson,et al.  Memory Function in Focal Epilepsy: A Comparison of Non-Surgical, Unilateral Temporal Lobe and Frontal Lobe Samples , 1980, Cortex.

[52]  Mark S. Seidenberg,et al.  Neuropsychological characteristics of the syndrome of mesial temporal lobe epilepsy. , 1997, Archives of neurology.

[53]  Robert K. Heaton,et al.  Wisconsin Card Sorting Test Manual – Revised and Expanded , 1993 .

[54]  Gregory McCarthy,et al.  Quantitative magnetic resonance imaging in temporal lobe epilepsy: Relationship to neuropathology and neuropsychological function , 1992, Annals of neurology.

[55]  Malcolm W. Brown,et al.  Recognition memory: What are the roles of the perirhinal cortex and hippocampus? , 2001, Nature Reviews Neuroscience.

[56]  Francis Eustache,et al.  Semantic and episodic memory of music are subserved by distinct neural networks , 2003, NeuroImage.

[57]  K. Meador,et al.  MRI hippocampal volume and neuropsychology in epilepsy surgery. , 1995, Magnetic resonance imaging.

[58]  C. Rorden,et al.  Stereotaxic display of brain lesions. , 2000, Behavioural neurology.

[59]  Hoi-Chung Leung,et al.  The effect of memory load on cortical activity in the spatial working memory circuit , 2004, Cognitive, affective & behavioral neuroscience.

[60]  T. L. Bennett Cognitive Effects of Epilepsy and Anticonvulsant Medications , 1992 .

[61]  L. Yeudall,et al.  Normative data for the Halstead-Reitan neuropsychological tests. , 1983, Journal of clinical neuropsychology.

[62]  S. Berkovic,et al.  Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects. , 1993, Journal of clinical and experimental neuropsychology.

[63]  S. Baxendale The hippocampus: Functional and structural correlations , 1995, Seizure.

[64]  Chris Rorden,et al.  Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy , 2005, NeuroImage.

[65]  D. Kimura Right temporal-lobe damage. Perception of unfamiliar stimuli after damage. , 1963, Archives of neurology.

[66]  R. Clark,et al.  The medial temporal lobe. , 2004, Annual review of neuroscience.

[67]  Leonardo Bonilha,et al.  Protocol for volumetric segmentation of medial temporal structures using high‐resolution 3‐D magnetic resonance imaging , 2004, Human brain mapping.

[68]  J. Malagón-Valdéz [Cognitive effects of antiepileptic drugs]. , 2003, Revista de neurologia.

[69]  S. Dikmen,et al.  The Effect of Early Versus Late Onset of Major Motor Epilepsy upon Cognitive‐Intellectual Performance , 1975, Epilepsia.

[70]  C Umiltà,et al.  Hemisphere‐dependent Cognitive Performances in Epileptic Patients , 1979, Epilepsia.