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ABSTRACT: Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment.
Brain 05/2013; · 9.46 Impact Factor
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ABSTRACT: PURPOSE: Postictal psychosis (PIP) occurs in ~7% of patients with temporal lobe epilepsy (TLE). The aims of this study were to identify risk factors that may predispose patients to developing PIP and determine whether the severity of PIP predicts postsurgical outcome. METHODS: We compared 20 patients with a history of TLE+PIP to 60 age-matched TLE patients without any psychiatric history (TLE-only), with respect to pre-surgical clinical and neuropsychological variables. Group differences in postsurgical psychiatric, histopathological, cognitive and seizure outcomes were also examined. KEY FINDINGS: TLE+PIP patients were significantly less likely to have localised ictal epileptiform activity than the TLE controls (p=0.05) and were significantly more likely to have a positive family psychiatric history than TLE controls (p=0.04). Other pre-surgical clinical and neuropsychological variables did not distinguish between the groups. Patients with two or more PIP episodes had significantly increased odds of developing de novo psychopathology within 4 years of surgery, after controlling for comorbid pre-surgical psychiatric status and a history of SGTCS (OR: 9.11, 95% CI: 1.53-54.10, p=0.02). A history of PIP did not significantly predict other postsurgical outcomes (seizure freedom (ILAE=1) or cognitive outcome). SIGNIFICANCE: Our results suggest that more widespread or diffuse brain abnormalities as reflected by pre-surgical EEG findings and positive genetic determinants may contribute to the development of PIP. Furthermore, patients with recurrent PIP episodes who undergo TLE surgery are at increased risk of developing de novo psychiatric disorders, particularly mood disorders. This has implications for pre-operative counselling and highlights a need for postsurgical psychiatric monitoring for these patients.
Epilepsy research 04/2013; · 2.48 Impact Factor
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ABSTRACT: PURPOSE: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. METHODS: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. KEY FINDINGS: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. SIGNIFICANCE: Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS.
Epilepsia 04/2013; · 3.96 Impact Factor
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ABSTRACT: Less than 3% of temporal lobe epilepsy (TLE) surgical outcome studies have investigated the psychiatric sequelae and morbidity associated with surgery. This is disproportionate to the extent of the problem. Variable prevalence rates have been reported for post-surgical depression, anxiety, and interictal psychosis. Until recently, very few studies distinguished de novo postoperative presentations from pre-existing conditions, making it difficult to accurately assess the impact of TLE surgery on psychiatric morbidity. Predictors of de novo postoperative presentations have proved elusive. This current review summarizes the findings from a systematic literature review of the psychiatric morbidity associated with TLE surgery including newly published follow-up data from our own series of 280 surgical patients. A framework for future research, possible pathophysiological mechanisms, and translational models are also discussed. This article is part of a Special Issue entitled "Translational Epilepsy Research".
Epilepsy & Behavior 12/2012; · 2.34 Impact Factor
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ABSTRACT: Purpose: Neurosurgery is an effective therapy for selected individuals with medically refractory temporal lobe epilepsy (TLE). De novo psychopathology may complicate the postsurgical outcome. Our aims were to identify predictors of de novo psychiatric and seizure outcome following TLE surgery. Methods: Medical records of 280 patients who underwent TLE surgery were reviewed. Preoperative and postoperative psychiatric diagnoses were identified, in addition to information on seizure recurrence and neuropsychological status. Logistic regression analysis was used to identify predictors of having a de novo psychiatric diagnosis and remaining seizure-free within 4 years following surgery. Key Findings: One hundred five patients (38%) had significant psychiatric problems within 4 years following TLE surgery. Fifty-one patients (18%) developed de novo psychopathology; half of cases presented within 6 months and 90% of psychopathologies persisted 6 months or longer. A preoperative history of secondary generalized tonic-clonic seizure(s) (SGTCS) was an independent predictor of de novo psychopathology (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.14-6.59, p = 0.02). From patients with available seizure data, 49% (127 of 258) remained seizure-free for 4 years after surgery. Patients with a history of SGTCS (OR 0.47, 95% CI 0.25-0.90, p = 0.02) and those with a preoperative psychiatric diagnosis (OR 0.53, 95% CI 0.28-0.98, p = 0.04) were significantly less likely to remain seizure-free. Significance: De novo psychopathology is a significant complication of TLE surgery. Inclusion of neuropsychiatric assessments in the presurgical evaluation may lead to increase in the power of prognostic models used to predict the neurologic outcome of TLE surgery.
Epilepsia 08/2012; 53(10):1705-12. · 3.96 Impact Factor
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ABSTRACT: To determine whether cortical abnormalities are more severe and widespread in patients with temporal lobe epilepsy (TLE) and interictal psychosis (IP) compared to those with TLE only (NIP) and healthy controls (HC), and to explore the associations between cortical parameters (area, thickness and volume), psychotic symptoms, and cognitive performance.
Twenty-two patients with IP (9 male; 10 hippocampal sclerosis, HS), 23 TLE nonpsychotic (NIP) patients (11 male; 13 HS) matched for duration of epilepsy and 20 HC participated. Surface-based morphometry (SBM) was used to measure cortical parameters. Cognition was examined in IP and NIP patients. Associations between cortical parameters and cognition were examined using linear mixed models adjusted by age, gender, and brain volume.
IP patients had an earlier onset of epilepsy, more status epilepticus, and worse cognitive performance than NIP patients. In IP patients, cortical thickness was reduced in the inferior frontal gyrus (IFG), and their current IQ was associated with decreases in area, but not thickness, in regions of the frontotemporal cortex.
IP likely reflects the interplay of psychosis-related genetic factors and the cumulative effects of seizure activity on the brain. Cortical thinning in the IFG, a region implicated in schizophrenia, is likely to be related to seizure activity, whereas changes in IQ, associated with reductions in area of frontotemporal cortex, may be related to the presence of psychosis.
Epilepsia 05/2012; 53(6):1077-87. · 3.96 Impact Factor
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ABSTRACT: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left-hemisphere-dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks.
We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE-MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR.
Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively.
In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.
Epilepsia 03/2012; 53(4):639-50. · 3.96 Impact Factor
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ABSTRACT: We examined the relationship between seizure outcomes and long-term changes in memory and intellectual function in 70 patients who had undergone temporal lobe resection for medically intractable epilepsy. Patients were assessed on four occasions: preoperatively (T1), 3 months postoperatively (T2), 1 year postoperatively (T3), and more than 5 years postoperatively (T4). The majority of patients had stable memory function across the assessments. However, many were functioning below the 15th percentile on the test norms preoperatively, with little capacity for further decline. All patients who demonstrated a progressive decline in verbal or visual learning were female and continued to experience seizures postoperatively. Progressive postoperative declines in memory function are associated with poor postoperative seizure control. These patterns can be obscured in group analyses that do not take into account baseline levels of function. Neuropsychological scores must be set in the context of the norms of the test and the associated capacity for further significant change over time to maximize the clinical relevance of long-term surgical follow-up studies.
Epilepsy & Behavior 11/2011; 23(1):24-9. · 2.34 Impact Factor
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Francesca I Arrigoni,
Mar Matarin, Pamela J Thompson,
Michel Michaelides,
Michelle E McClements,
Elizabeth Redmond,
Lindsey Clarke,
Elizabeth Ellins,
Saifullah Mohamed,
Ian Pavord,
Nigel Klein,
David M Hunt,
Anthony T Moore,
Julian Halcox,
Sanjay M Sisodiya
European journal of human genetics: EJHG 09/2011; 19(9):1018. · 3.56 Impact Factor
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Silvia B Bonelli,
Rob Powell, Pamela J Thompson,
Mahinda Yogarajah,
Niels K Focke,
Jason Stretton,
Christian Vollmar,
Mark R Symms,
Cathy J Price,
John S Duncan,
Matthias J Koepp
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ABSTRACT: In patients with left temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) decreased naming ability is common, suggesting a critical role for the medial left temporal lobe in this task. We investigated the integrity of language networks with functional MRI (fMRI) in controls and TLE patients.
We performed an fMRI verbal fluency paradigm in 22 controls and 66 patients with unilateral mesial TLE (37 left HS, 29 right HS). Verbal fluency and naming ability were investigated as part of the standard presurgical neuropsychological assessment. Naming ability was assessed using a visual confrontation naming test.
Left TLE patients had significantly lower naming scores than controls and those with right TLE. Right TLE patients performed less well than controls, but better than those with left TLE. Left TLE had significantly lower scores for verbal fluency than controls. In controls and right TLE, left hippocampal activation during the verbal fluency task was significantly correlated with naming, characterised by higher scores in subjects with greater hippocampal fMRI activation. In left TLE no correlation with naming scores was seen in the left hippocampus, but there was a significant correlation in the left middle and inferior frontal gyri, not observed in controls and right TLE. In left and right TLE, out of scanner verbal fluency scores significantly correlated with fMRI activation for verbal fluency in the left middle and inferior frontal gyri.
Good confrontation naming ability depends on the integrity of the hippocampus and the connecting fronto-temporal networks. Functional MRI activation in the left hippocampus during verbal fluency is associated with naming function in healthy controls and patients with right TLE. In left TLE, there was evidence of involvement of the left frontal lobe when naming was more proficient, most likely reflecting a compensatory response due to the ongoing epileptic activity and/or underlying pathology.
Epilepsy research 05/2011; 95(3):246-54. · 2.48 Impact Factor
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Francesca I Arrigoni,
Mar Matarin, Pamela J Thompson,
Michel Michaelides,
Michelle E McClements,
Elizabeth Redmond,
Lindsey Clarke,
Elizabeth Ellins,
Saifullah Mohamed,
Ian Pavord,
Nigel Klein,
David M Hunt,
Anthony T Moore,
Julian Halcox,
Sanjay M Sisodiya
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ABSTRACT: Mutations in prominin 1 (PROM1) have been shown to result in retinitis pigmentosa, macular degeneration and cone-rod dystrophy. Because of the putative role of PROM1 in hippocampal neurogenesis, we examined two kindreds with the same R373C PROM1 missense mutation using our established paradigm to study brain structure and function. As the protein encoded by PROM1, known as CD133, is used to identify stem/progenitor cells that can be found in peripheral blood and reflect endothelial reparatory mechanisms, other parameters were subsequently examined that included measures of vascular function, endothelial function and angiogenic capacity. We found that aspects of endothelial function assayed ex vivo were abnormal in patients with the R373C PROM1 mutation, with impaired adhesion capacity and higher levels of cellular damage. We also noted renal infections, haematuria and recurrent miscarriages possibly reflecting consequences of abnormal tubular modelling. Further studies are needed to confirm these findings.
European journal of human genetics: EJHG 02/2011; 19(2):131-7. · 3.56 Impact Factor
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ABSTRACT: To examine the influence of side of pathology and gender on changes in cognitive function across the adult lifespan in a homogenous sample of patients with mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS).
We retrospectively examined the neuropsychological profiles of 382 patients in 3 cohorts: cohort 1 aged 18-30 (n = 171), cohort 2 aged 31-45 (n = 170), and cohort 3 aged 46-65 (n = 41). All participants had medically intractable seizures associated with unilateral HS and an onset of epilepsy in childhood, with an average onset at 7 years.
There were no significant differences between the age cohorts on the measures of intellect, language, or memory. Duration of epilepsy (years) was not related to IQ, memory, or language scores in any group. Male subjects performed better than female subjects on verbal IQ, performance IQ, and naming tasks. Verbal learning and recall scores were worse in those with left than right HS.
Our findings suggest that the profile of cognitive deficits associated with MTLE is already established as children with temporal lobe epilepsy enter adulthood. While memory and language skills are maximally affected, intellectual function is also compromised in MTLE. This profile appears to remain stable across the adult lifespan, at least until 60 years of age, despite the intractable nature of the seizures. Side of pathology and gender are significant mediating factors in shaping the profile of cognitive deficits associated with childhood-onset MTLE, with people with left-sided HS and female subjects particularly vulnerable to more widespread cognitive dysfunction.
Neurology 08/2010; 75(8):705-11. · 8.31 Impact Factor
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ABSTRACT: Functional magnetic resonance imaging can demonstrate the functional anatomy of cognitive processes. In patients with refractory temporal lobe epilepsy, evaluation of preoperative verbal and visual memory function is important as anterior temporal lobe resections may result in material specific memory impairment, typically verbal memory decline following left and visual memory decline after right anterior temporal lobe resection. This study aimed to investigate reorganization of memory functions in temporal lobe epilepsy and to determine whether preoperative memory functional magnetic resonance imaging may predict memory changes following anterior temporal lobe resection. We studied 72 patients with unilateral medial temporal lobe epilepsy (41 left) and 20 healthy controls. A functional magnetic resonance imaging memory encoding paradigm for pictures, words and faces was used testing verbal and visual memory in a single scanning session on a 3T magnetic resonance imaging scanner. Fifty-four patients subsequently underwent left (29) or right (25) anterior temporal lobe resection. Verbal and design learning were assessed before and 4 months after surgery. Event-related functional magnetic resonance imaging analysis revealed that in left temporal lobe epilepsy, greater left hippocampal activation for word encoding correlated with better verbal memory. In right temporal lobe epilepsy, greater right hippocampal activation for face encoding correlated with better visual memory. In left temporal lobe epilepsy, greater left than right anterior hippocampal activation on word encoding correlated with greater verbal memory decline after left anterior temporal lobe resection, while greater left than right posterior hippocampal activation correlated with better postoperative verbal memory outcome. In right temporal lobe epilepsy, greater right than left anterior hippocampal functional magnetic resonance imaging activation on face encoding predicted greater visual memory decline after right anterior temporal lobe resection, while greater right than left posterior hippocampal activation correlated with better visual memory outcome. Stepwise linear regression identified asymmetry of activation for encoding words and faces in the ipsilateral anterior medial temporal lobe as strongest predictors for postoperative verbal and visual memory decline. Activation asymmetry, language lateralization and performance on preoperative neuropsychological tests predicted clinically significant verbal memory decline in all patients who underwent left anterior temporal lobe resection, but were less able to predict visual memory decline after right anterior temporal lobe resection. Preoperative memory functional magnetic resonance imaging was the strongest predictor of verbal and visual memory decline following anterior temporal lobe resection. Preoperatively, verbal and visual memory function utilized the damaged, ipsilateral hippocampus and also the contralateral hippocampus. Memory function in the ipsilateral posterior hippocampus may contribute to better preservation of memory after surgery.
Brain 02/2010; 133(Pt 4):1186-99. · 9.46 Impact Factor
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ABSTRACT: While up to a third of patients may experience a decline in memory following an anterior temporal lobe resection (ATL) for epilepsy, between 10 and 20% may experience a postoperative improvement in function. The aim of this study was to examine the preoperative characteristics of these patients.
Logistic regression analyses were used to determine which variables influenced postoperative memory improvement following ATL on standardized memory tests in 237 patients with unilateral hippocampal sclerosis (105 right; 132 left).
A total of 22% of the right ATL and 9% of the left ATL group demonstrated a significant postoperative improvement in verbal learning. A total of 9% of the right ATL and 16% of the left ATL group demonstrated a significant postoperative improvement in visual learning. In the R ATL group, postoperative improvements in verbal learning were associated with poor preoperative verbal learning, a shorter duration of epilepsy, higher scores on the visual learning task, and an older age at the time of surgery. In the L ATL group, postoperative improvements in visual learning were associated with poor preoperative visual learning, a shorter duration of epilepsy, and a higher IQ. Postoperative improvements in memory functions associated with the ipsilateral temporal lobe were not associated with demographic or epilepsy-related variables.
Memory deficits normally associated with the function of the contralateral temporal lobe in patients with unilateral hippocampal sclerosis may improve postoperatively in patients with a shorter duration of epilepsy and the cognitive capacity to develop compensatory strategies.
Neurology 10/2008; 71(17):1319-25. · 8.31 Impact Factor
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ABSTRACT: Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.
Epilepsia 09/2008; 50(2):217-27. · 3.96 Impact Factor
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Archives of neurology 07/2008; 65(6):841-5. · 6.31 Impact Factor
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Epilepsia 05/2008; 49(4):715-20; discussion 720-5. · 3.96 Impact Factor
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Sanjay M Sisodiya, Pamela J Thompson,
Anna Need,
Sarah E Harris,
Michael E Weale,
Susan E Wilkie,
Michel Michaelides,
Samantha L Free,
Nicole Walley,
Curtis Gumbs,
Dianne Gerrelli,
Piers Ruddle,
Lawrence J Whalley,
John M Starr,
David M Hunt,
David B Goldstein,
Ian J Deary,
Anthony T Moore
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ABSTRACT: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active-zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function.
An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation. Materials and
Neuropsychological tests and high-resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top-scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied.
Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man.
A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases.
Journal of Medical Genetics 07/2007; 44(6):373-80. · 6.36 Impact Factor
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ABSTRACT: People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these increases in unrelated deaths and comorbid conditions is unclear. In this article, we argue that having seizures is psychologically stressful, and that this stress can lead to a whole range of pathophysiological changes that may trigger various physical illnesses. Hence, psychological stress may be a significant factor contributing to the increase in mortality and comorbidity rates in PWE. This speculation is unlikely to be proven at this stage because of the complexity of the trials required. In PWE who continue to have seizures, more needs to be done to help them cope with the stress. Additionally, attention needs to be paid to improve nutritional status and physical fitness. These steps are likely to enhance the overall health of PWE and may reduce premature mortality and comorbidity rates.
Epilepsy & Behavior 03/2007; 10(1):1-7. · 2.34 Impact Factor
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ABSTRACT: To characterize the pattern of cognitive deficits in patients with temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to examine the relationship between neuropsychological deficits and Magnetization transfer imaging.
Twenty patients with TLE and interictal psychosis were compared to 20 non-psychotic TLE patients. Patients were matched with respect to premorbid IQ, age and conventional MRI findings. A battery of neuropsychological tests was administered. The neuropsychological tests which showed significant group differences were used for correlational analysis with magnetization transfer ratio (MTR) which provides a quantitative measure of macromolecular structural integrity.
Patients with interictal psychosis were significantly more impaired on executive and semantic memory tasks than the non-psychotic TLE group. Vocabulary test scores correlated significantly with MTR reduction in the left fusiform gyrus in the psychotic but not the non-psychotic group.
In this study, patients with TLE and interictal psychosis were more cognitively impaired than non-psychotic TLE patients. Our findings suggest that the cognitive deterioration in these patients may occur as the illness progresses and the causes for this are probably multifactorial. Our study also provides further evidence that MTR may be useful in investigating structural correlates of cognitive impairment.
Epilepsy Research 11/2006; 71(2-3):117-28. · 2.29 Impact Factor
