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Epilepsy: HELP
Articles by Meneka Kaur Sidhu
Based on 19 articles published since 2010
(Why 19 articles?)
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Between 2010 and 2020, M. Sidhu wrote the following 19 articles about Epilepsy.
 
+ Citations + Abstracts
1 Review Neuroimaging in epilepsy. 2018

Sidhu, Meneka Kaur / Duncan, John S / Sander, Josemir W. ·Department of Clinical and Experimental Epilepsy, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Institute of Neurology, University College London, London. · Chalfont Centre for Epilepsy, Chesham Lane, Chalfont St. Peter, Gerrards Cross, UK. · Stichting Epilepsie Instellngen Nederland, Achterweg 5, Heemstede, The Netherlands. ·Curr Opin Neurol · Pubmed #29782369.

ABSTRACT: PURPOSE OF REVIEW: Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. RECENT FINDINGS: The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance.Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. SUMMARY: Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy.

2 Article Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings. 2019

Caciagli, Lorenzo / Wandschneider, Britta / Xiao, Fenglai / Vollmar, Christian / Centeno, Maria / Vos, Sjoerd B / Trimmel, Karin / Sidhu, Meneka K / Thompson, Pamela J / Winston, Gavin P / Duncan, John S / Koepp, Matthias J. ·Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, Queen Square, London, UK. · MRI Unit, Epilepsy Society, Chalfont St Peter, Buckinghamshire, UK. · Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, China. · Department of Neurology, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich, Germany. · Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, UK. · Centre for Medical Image Computing, University College London, London, UK. · Department of Neurology, Medical University of Vienna, Vienna, Austria. · Department of Medicine, Division of Neurology, Queen's University, Kingston, Ontario, Canada. ·Brain · Pubmed #31365054.

ABSTRACT: Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.

3 Article The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy. 2019

Sidhu, Meneka K / Thompson, Pamela J / Wandschneider, Britta / Foulkes, Alexandra / de Tisi, Jane / Stretton, Jason / Perona, Marina / Thom, Maria / Bonelli, Silvia B / Burdett, Jane / Williams, Elaine / Duncan, John S / Matarin, Mar. ·Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK. · Epilepsy Society MRI Unit, Chesham Lane, Buckinghamshire, UK. · Department of Radiobiology (CAC), National Atomic Energy Commission (CNEA), National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina. · Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. ·CNS Neurosci Ther · Pubmed #29952080.

ABSTRACT: INTRODUCTION: Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. AIMS: We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. METHODS: In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). RESULTS: mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. CONCLUSIONS: Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE.

4 Article Effects of carbamazepine and lamotrigine on functional magnetic resonance imaging cognitive networks. 2018

Xiao, Fenglai / Caciagli, Lorenzo / Wandschneider, Britta / Sander, Josemir W / Sidhu, Meneka / Winston, Gavin / Burdett, Jane / Trimmel, Karin / Hill, Andrea / Vollmar, Christian / Vos, Sjoerd B / Ourselin, Sebastien / Thompson, Pamela J / Zhou, Dong / Duncan, John S / Koepp, Matthias J. ·Department of Clinical and Experimental Epilepsy, University College London Institute of Neurology, London, UK. · Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, China. · Magnetic Resonance Imaging Unit, Epilepsy Society, Gerrards Cross, UK. · Department of Neurology, Medical University of Vienna, Vienna, Austria. · Department of Neurology, Epilepsy Center, University of Munich, Munich, Germany. · Wellcome/Engineering and Physical Sciences Research Council Centre for Interventional and Surgical Sciences, University College London, London, UK. · Translational Imaging Group, University College London, London, UK. ·Epilepsia · Pubmed #29897625.

ABSTRACT: OBJECTIVE: To investigate the effects of sodium channel-blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy. METHODS: In a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel-blocking AED. We propensity-matched 42 patients taking levetiracetam (LEV) as "patient-controls" and included further 42 age- and gender-matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out-of-scanner psychometric measures of verbal fluency. RESULTS: Patients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV-treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out-of-scanner fluency scores correlated positively with left putamen activation. SIGNIFICANCE: Our study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well-tolerated sodium channel-blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task-negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks.

5 Article Memory network plasticity after temporal lobe resection: a longitudinal functional imaging study. 2016

Sidhu, Meneka K / Stretton, Jason / Winston, Gavin P / McEvoy, Andrew W / Symms, Mark / Thompson, Pamela J / Koepp, Matthias J / Duncan, John S. ·1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK 2 Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, Buckinghamshire, UK. · 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK 2 Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, Buckinghamshire, UK 3 MRC Cognition and Brain Science Unit, Chaucer Road, Cambridge, CB2 7EF, UK. · 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK 2 Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, Buckinghamshire, UK j.duncan@ucl.ac.uk. ·Brain · Pubmed #26754787.

ABSTRACT: Anterior temporal lobe resection can control seizures in up to 80% of patients with temporal lobe epilepsy. Memory decrements are the main neurocognitive complication. Preoperative functional reorganization has been described in memory networks, but less is known of postoperative reorganization. We investigated reorganization of memory-encoding networks preoperatively and 3 and 12 months after surgery. We studied 36 patients with unilateral medial temporal lobe epilepsy (19 right) before and 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were studied at three equivalent time points. All subjects had neuropsychological testing at each of the three time points. A functional magnetic resonance imaging memory-encoding paradigm of words and faces was performed with subsequent out-of-scanner recognition assessments. Changes in activations across the time points in each patient group were compared to changes in the control group in a single flexible factorial analysis. Postoperative change in memory across the time points was correlated with postoperative activations to investigate the efficiency of reorganized networks. Left temporal lobe epilepsy patients showed increased right anterior hippocampal and frontal activation at both 3 and 12 months after surgery relative to preoperatively, for word and face encoding, with a concomitant reduction in left frontal activation 12 months postoperatively. Right anterior hippocampal activation 12 months postoperatively correlated significantly with improved verbal learning in patients with left temporal lobe epilepsy from preoperatively to 12 months postoperatively. Preoperatively, there was significant left posterior hippocampal activation that was sustained 3 months postoperatively at word encoding, and increased at face encoding. For both word and face encoding this was significantly reduced from 3 to 12 months postoperatively. Patients with right temporal lobe epilepsy showed increased left anterior hippocampal activation on word encoding from 3 to 12 months postoperatively compared to preoperatively. On face encoding, left anterior hippocampal activations were present preoperatively and 12 months postoperatively. Left anterior hippocampal and orbitofrontal cortex activations correlated with improvements in both design and verbal learning 12 months postoperatively. On face encoding, there were significantly increased left posterior hippocampal activations that reduced significantly from 3 to 12 months postoperatively. Postoperative changes occur in the memory-encoding network in both left and right temporal lobe epilepsy patients across both verbal and visual domains. Three months after surgery, compensatory posterior hippocampal reorganization that occurs is transient and inefficient. Engagement of the contralateral hippocampus 12 months after surgery represented efficient reorganization in both patient groups, suggesting that the contralateral hippocampus contributes to memory outcome 12 months after surgery.

6 Article Meyer's loop asymmetry and language lateralisation in epilepsy. 2016

Nowell, Mark / Vos, Sjoerd B / Sidhu, Meneka / Wilcoxen, Kaitlin / Sargsyan, Narek / Ourselin, Sebastien / Duncan, John S. ·Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St Peter, UK. · MRI Unit, Epilepsy Society, Chalfont St Peter, UK Translational Imaging Group, Centre of Medical Imaging and Computing, UCL, London, UK. · MRI Unit, Epilepsy Society, Chalfont St Peter, UK. · Translational Imaging Group, Centre of Medical Imaging and Computing, UCL, London, UK. ·J Neurol Neurosurg Psychiatry · Pubmed #26384513.

ABSTRACT: OBJECTIVES: Several studies have suggested an asymmetry in Meyer's loop in individuals, with the left loop anterior to the right. In this study we test the hypothesis that there is an association between Meyer's loop asymmetry (MLA) and language lateralisation. METHODS: 57 patients with epilepsy were identified with language functional MRI (fMRI) and diffusion MRI acquisition. Language lateralisation indices from fMRI(LI) and optic radiation and arcuate fasciculus probabilistic tractography was performed for each subject. The subjects were divided into left language dominant (LI>0.4) and non-left language groups (LI<0.4) according to their LI. RESULTS: A negative linear correlation was identified between language lateralisation and MLA, with greater left lateralised language associated with more anteriorly placed left Meyer's loops (R value -0.34, p=0.01). There was a significant difference in mean MLA between the two groups, with the left loop being anterior to the right loop in the LI>0.4 group and posterior to the right loop in the LI<0.4 group (p=0.003). No correlation was found between language lateralisation and arcuate fasciculus volume. CONCLUSIONS: This study suggests an association between the extent of Meyer's loop asymmetry and the lateralisation of language determined by fMRI in patients with epilepsy. Further studies should be carried out to evaluate this association in control subjects and with other measures of language lateralisation.

7 Article Memory fMRI predicts verbal memory decline after anterior temporal lobe resection. 2015

Sidhu, Meneka K / Stretton, Jason / Winston, Gavin P / Symms, Mark / Thompson, Pamela J / Koepp, Matthias J / Duncan, John S. ·From the Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London; and the Epilepsy Society MRI Unit, Chalfont St. Peter, UK. ·Neurology · Pubmed #25770199.

ABSTRACT: OBJECTIVE: To develop a clinically applicable memory functional MRI (fMRI) method of predicting postsurgical memory outcome in individual patients. METHODS: In this prospective cohort study, 50 patients with temporal lobe epilepsy (23 left) and 26 controls underwent an fMRI memory encoding paradigm of words with a subsequent out-of-scanner recognition assessment. Neuropsychological assessment was performed preoperatively and 4 months after anterior temporal lobe resection, and at equal time intervals in controls. An event-related analysis was used to explore brain activations for words remembered and change in verbal memory scores 4 months after surgery was correlated with preoperative activations. Individual lateralization indices were calculated within a medial temporal and frontal region and compared with other clinical parameters (hippocampal volume, preoperative verbal memory, age at onset of epilepsy, and language lateralization) as a predictor of verbal memory outcome. RESULTS: In left temporal lobe epilepsy patients, left frontal and anterior medial temporal activations correlated significantly with greater verbal memory decline, while bilateral posterior hippocampal activation correlated with less verbal memory decline postoperatively. In a multivariate regression model, left lateralized memory lateralization index (≥0.5) within a medial temporal and frontal mask was the best predictor of verbal memory outcome after surgery in the dominant hemisphere in individual patients. Neither clinical nor functional MRI parameters predicted verbal memory decline after nondominant temporal lobe resection. CONCLUSION: We propose a clinically applicable memory fMRI paradigm to predict postoperative verbal memory decline after surgery in the language-dominant hemisphere in individual patients.

8 Article Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy. 2015

Sidhu, M K / Stretton, J / Winston, G P / Symms, M / Thompson, P J / Koepp, M J / Duncan, J S. ·Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: m.sidhu@ucl.ac.uk. · Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: j.stretton@ucl.ac.uk. · Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: g.winston@ucl.ac.uk. · Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: m.symms@ucl.ac.uk. · Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: p.thompson@ucl.ac.uk. · Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: m.koepp@ucl.ac.uk. · Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1 N 3BG, UK; Epilepsy Society MRI Unit, Chesham Lane, Chalfont St. Peter SL9 0RJ, UK. Electronic address: j.duncan@ucl.ac.uk. ·Epilepsy Res · Pubmed #25616449.

ABSTRACT: AIMS: In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. METHODS: We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. RESULTS: Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. CONCLUSION: Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation.

9 Article Temporal lobe epilepsy and affective disorders: the role of the subgenual anterior cingulate cortex. 2015

Stretton, J / Pope, R A / Winston, G P / Sidhu, M K / Symms, M / Duncan, J S / Koepp, M / Thompson, P J / Foong, J. ·Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK MRC Cognition and Brain Science Unit, Cambridge, UK. · Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK Clinical Psychopharmacology Unit, University College London, London, UK. · Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK. ·J Neurol Neurosurg Psychiatry · Pubmed #24876189.

ABSTRACT: OBJECTIVE: Reduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present in temporal lobe epilepsy (TLE) patients with a history of affective psychopathology. METHODS: 17 TLE patients with a lifetime affective diagnosis, 31 TLE patients with no formal psychiatric history and 30 HVs were included. We used a visuo-spatial 'n-back' paradigm to compare working memory (WM) network activation between these groups. Post hoc analyses included voxel-based morphometry and diffusion tensor imaging. The Beck Depression Inventory-Fast Screen and Beck Anxiety Inventory were completed on the day of scanning. FINDINGS: Each group activated the fronto-parietal WM networks and deactivated the typical DMN in response to increasing task demands. Group comparison revealed that TLE patients with lifetime affective morbidity showed significantly greater deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE-only or the HVs (p<0.001). This effect persisted after covarying for current psychotropic medication and severity of current depressive/anxiety symptoms (all p<0.001). Correlational analysis revealed that this finding was not driven by differences in task performance. There were no significant differences in grey matter volume or structural connectivity between the TLE groups. CONCLUSIONS: Our results provide novel evidence suggesting that affective psychopathology in TLE has a neurobiological correlate, and in this context the sACC performs differently compared with network activity in primary affective disorders.

10 Article Levetiracetam reduces abnormal network activations in temporal lobe epilepsy. 2014

Wandschneider, Britta / Stretton, Jason / Sidhu, Meneka / Centeno, Maria / Kozák, Lajos R / Symms, Mark / Thompson, Pamela J / Duncan, John S / Koepp, Matthias J. ·From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London · the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge · the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK · and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary. ·Neurology · Pubmed #25253743.

ABSTRACT: OBJECTIVE: We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). METHODS: In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. RESULTS: We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. CONCLUSIONS: Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures.

11 Article Language dominance assessment in a bilingual population: validity of fMRI in the second language. 2014

Centeno, Maria / Koepp, Matthias J / Vollmar, Christian / Stretton, Jason / Sidhu, Meneka / Michallef, Caroline / Symms, Mark R / Thompson, Pamela J / Duncan, John S. ·Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, MRI Unit. Epilepsy Society, Chalfont St Peter, United Kingdom; Medicine Department, Neurology section, University Hospital, Universitat Autonomous University of Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain. ·Epilepsia · Pubmed #25182478.

ABSTRACT: OBJECTIVE: Assessment of language dominance using functional magnetic resonance imaging (fMRI) is a standard tool to estimate the risk of language function decline after epilepsy surgery. Although there has been considerable research in the characterization of language networks in bilingual individuals; little is known about the clinical usefulness of language mapping in a secondary language in patients with epilepsy, and how language lateralization assessed by fMRI may differ by the use of native or a secondary language paradigms. In this study we investigate language representation in a population of nonnative English speakers to assess differences in fMRI language lateralization between the first (native) and second language (English). METHODS: Sixteen nonnative English-speaking patients with focal drug-resistant epilepsy underwent language fMRI in their first (native) language (L1) and in English (L2). Differences between language maps using L1 and L2 paradigms were examined at the single subject level by comparing within-subject lateralization indexes obtained for each language. Differences at the group level were examined for each of the tasks and languages. RESULTS: Group maps for the second language (English) showed overlapping areas of activation with the native language, but with larger clusters, and more bilaterally distributed than for the first language. However, at the individual level, lateralization indexes were concordant between the two languages, except for one patient with bilateral hippocampal sclerosis who was left dominant in English and showed bilateral dominance for verb generation and right dominance for verbal fluency in his native tongue. SIGNIFICANCE: Language lateralization can generally be reliably derived from fMRI tasks in a second language provided that the subject can follow the task. Subjects with greater likelihood of atypical language representation should be evaluated more carefully, using more than one language paradigm.

12 Article Preventing visual field deficits from neurosurgery. 2014

Winston, Gavin P / Daga, Pankaj / White, Mark J / Micallef, Caroline / Miserocchi, Anna / Mancini, Laura / Modat, Marc / Stretton, Jason / Sidhu, Meneka K / Symms, Mark R / Lythgoe, David J / Thornton, John / Yousry, Tarek A / Ourselin, Sebastien / Duncan, John S / McEvoy, Andrew W. ·From the Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy (G.P.W., J.S., M.K.S., M.R.S., J.S.D.), and the Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation (M.J.W., C.M., L.M., J.T. , T.A.Y.), UCL Institute of Neurology · the UCL Centre for Medical Image Computing (P.D., M.M., S.O.) · the Lysholm Department of Neuroradiology (M.J.W., C.M., L.M., J.T., T.A.Y.) and the Department of Neurosurgery (A.M., A.W.M.), National Hospital for Neurology and Neurosurgery · and Kings College London (D.J.L.), Institute of Psychiatry, Centre for Neuroimaging Sciences, London, UK. ·Neurology · Pubmed #25015363.

ABSTRACT: OBJECTIVE: We assessed whether display of optic radiation tractography during anterior temporal lobe resection (ATLR) for refractory temporal lobe epilepsy (TLE) can reduce the severity of postoperative visual field deficits (VFD) and increase the proportion of patients who can drive and whether correction for brain shift using intraoperative MRI (iMRI) is beneficial. METHODS: A cohort of 21 patients underwent ATLR in an iMRI suite. Preoperative tractography of the optic radiation was displayed on the navigation and operating microscope displays either without (9 patients) or with (12 patients) correction for brain shift. VFD were quantified using Goldmann perimetry and eligibility to drive was assessed by binocular Esterman perimetry 3 months after surgery. Secondary outcomes included seizure freedom and extent of hippocampal resection. The comparator was a cohort of 44 patients who underwent ATLR without iMRI. RESULTS: The VFD in the contralateral superior quadrant were significantly less (p = 0.043) with iMRI guidance (0%-49.2%, median 14.5%) than without (0%-90.9%, median 24.0%). No patient in the iMRI cohort developed a VFD that precluded driving whereas 13% of the non-iMRI cohort failed to meet UK driving criteria. Outcome did not differ between iMRI guidance with and without brain shift correction. Seizure outcome and degree of hippocampal resection were unchanged. CONCLUSIONS: Display of the optic radiation with image guidance reduces the severity of VFD and did not affect seizure outcome or hippocampal resection. Correction for brain shift is possible but did not further improve outcome. Future work to incorporate tractography into conventional neuronavigation systems will make the work more widely applicable.

13 Article Working memory network plasticity after anterior temporal lobe resection: a longitudinal functional magnetic resonance imaging study. 2014

Stretton, Jason / Sidhu, Meneka K / Winston, Gavin P / Bartlett, Philippa / McEvoy, Andrew W / Symms, Mark R / Koepp, Matthias J / Thompson, Pamela J / Duncan, John S. ·1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. ·Brain · Pubmed #24691395.

ABSTRACT: Working memory is a crucial cognitive function that is disrupted in temporal lobe epilepsy. It is unclear whether this impairment is a consequence of temporal lobe involvement in working memory processes or due to seizure spread to extratemporal eloquent cortex. Anterior temporal lobe resection controls seizures in 50-80% of patients with drug-resistant temporal lobe epilepsy and the effect of surgery on working memory are poorly understood both at a behavioural and neural level. We investigated the impact of temporal lobe resection on the efficiency and functional anatomy of working memory networks. We studied 33 patients with unilateral medial temporal lobe epilepsy (16 left) before, 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were also assessed in parallel. All subjects had neuropsychological testing and performed a visuospatial working memory functional magnetic resonance imaging paradigm on these three separate occasions. Changes in activation and deactivation patterns were modelled individually and compared between groups. Changes in task performance were included as regressors of interest to assess the efficiency of changes in the networks. Left and right temporal lobe epilepsy patients were impaired on preoperative measures of working memory compared to controls. Working memory performance did not decline following left or right temporal lobe resection, but improved at 3 and 12 months following left and, to a lesser extent, following right anterior temporal lobe resection. After left anterior temporal lobe resection, improved performance correlated with greater deactivation of the left hippocampal remnant and the contralateral right hippocampus. There was a failure of increased deactivation of the left hippocampal remnant at 3 months after left temporal lobe resection compared to control subjects, which had normalized 12 months after surgery. Following right anterior temporal lobe resection there was a progressive increase of activation in the right superior parietal lobe at 3 and 12 months after surgery. There was greater deactivation of the right hippocampal remnant compared to controls between 3 and 12 months after right anterior temporal lobe resection that was associated with lesser improvement in task performance. Working memory improved after anterior temporal lobe resection, particularly following left-sided resections. Postoperative working memory was reliant on the functional capacity of the hippocampal remnant and, following left resections, the functional reserve of the right hippocampus. These data suggest that working memory following temporal lobe resection is dependent on the engagement of the posterior medial temporal lobes and eloquent cortex.

14 Article Progressive white matter changes following anterior temporal lobe resection for epilepsy. 2014

Winston, Gavin P / Stretton, Jason / Sidhu, Meneka K / Symms, Mark R / Duncan, John S. ·Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, England, UK. ·Neuroimage Clin · Pubmed #24392306.

ABSTRACT: Anterior temporal lobe resection (ATLR) is an effective treatment for refractory temporal lobe epilepsy (TLE). Widespread abnormalities in diffusion parameters involving the ipsilateral temporal lobe white matter and extending into extratemporal white matter have been shown in cross-sectional studies in TLE. However longitudinal changes following surgery have been less well addressed. We systematically assess diffusion changes in white matter in patients with TLE in comparison to controls before surgery and look at the longitudinal changes following ATLR at two timepoints (3-4 months, 12 months) using a whole brain approach. We find predominantly unilateral baseline changes in temporal and extratemporal structures compatible with altered myelination (reduced fractional anisotropy, increased mean and radial diffusivity). Following surgery, these changes progress in efferent tracts from the resected temporal lobe compatible with Wallerian degeneration. However more superiorly in the corona radiata, internal and external capsules and nearby tracts, changes compatible with plasticity are observed (increased fractional anisotropy and axial diffusivity, reduced radial diffusivity). There is little progression between 3-4 months and 12 months following surgery in patients with left TLE, but the changes become more widespread in patients with right TLE suggesting that plasticity occurs more slowly in this population. The neuropsychological correlates of such plasticity should be explored further.

15 Article Disrupted segregation of working memory networks in temporal lobe epilepsy. 2013

Stretton, J / Winston, G P / Sidhu, M / Bonelli, S / Centeno, M / Vollmar, C / Cleary, R A / Williams, E / Symms, M R / Koepp, M J / Thompson, P J / Duncan, J S. ·Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. ·Neuroimage Clin · Pubmed #24179782.

ABSTRACT: Working memory is a critical building block for almost all cognitive tasks, and impairment can cause significant disruption to daily life routines. We investigated the functional connectivity (FC) of the visuo-spatial working memory network in temporal lobe epilepsy and its relationship to the underlying white matter tracts emanating from the hippocampus. Fifty-two patients with unilateral hippocampal sclerosis (HS) (30 left) and 30 healthy controls underwent working memory functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). Six seed regions were identified for FC analysis; 4 within a task-positive network (left and right middle frontal gyri and superior parietal lobes), and 2 within a task-negative network (left and right hippocampi). FC maps were created by extracting the time-series of the fMRI signal in each region in each subject and were used as regressors of interest for additional GLM fMRI analyses. Structural connectivity (SC) corresponding to areas to which the left and right hippocampi were connected was determined using tractography, and a mean FA for each hippocampal SC map was calculated. Both left and right HS groups showed atypical FC between task-positive and task-negative networks compared to controls. This was characterised by co-activation of the task-positive superior parietal lobe ipsilateral to the typically task-negative sclerosed hippocampus. Correlational analysis revealed stronger FC between superior parietal lobe and ipsilateral hippocampus, was associated with worse performance in each patient group. The SC of the hippocampus was associated with the intra-hemispheric FC of the superior parietal lobe, in that greater SC was associated with weaker parieto-frontal FC. The findings suggest that the segregation of the task-positive and task-negative FC networks supporting working memory in TLE is disrupted, and is associated with abnormal structural connectivity of the sclerosed hippocampus. Co-activation of parieto-temporal regions was associated with poorer working memory and this may be associated with working memory dysfunction in TLE.

16 Article A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy. 2013

Sidhu, Meneka K / Stretton, Jason / Winston, Gavin P / Bonelli, Silvia / Centeno, Maria / Vollmar, Christian / Symms, Mark / Thompson, Pamela J / Koepp, Matthias J / Duncan, John S. ·Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. ·Brain · Pubmed #23674488.

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.

17 Article Structural correlates of impaired working memory in hippocampal sclerosis. 2013

Winston, Gavin P / Stretton, Jason / Sidhu, Meneka K / Symms, Mark R / Thompson, Pamela J / Duncan, John S. ·Epilepsy Society MRI Unit, Chesham Lane, Chalfont St Peter, United Kingdom. g.winston@ucl.ac.uk ·Epilepsia · Pubmed #23614459.

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.

18 Article Assessing hippocampal functional reserve in temporal lobe epilepsy: a multi-voxel pattern analysis of fMRI data. 2013

Bonnici, Heidi M / Sidhu, Meneka / Chadwick, Martin J / Duncan, John S / Maguire, Eleanor A. ·Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, 12 Queen Square, London WC1N 3BG, United Kingdom. ·Epilepsy Res · Pubmed #23352740.

ABSTRACT: Assessing the functional reserve of key memory structures in the medial temporal lobes (MTL) of pre-surgical patients with intractable temporal lobe epilepsy (TLE) remains a challenge. Conventional functional MRI (fMRI) memory paradigms have yet to fully convince of their ability to confidently assess the risk of a post-surgical amnesia. An alternative fMRI analysis method, multi-voxel pattern analysis (MVPA), focuses on the patterns of activity across voxels in specific brain regions that are associated with individual memory traces. This method makes it possible to investigate whether the hippocampus and related structures contralateral to any proposed surgery are capable of laying down and representing specific memories. Here we used MVPA-fMRI to assess the functional integrity of the hippocampi and MTL in patients with long-standing medically refractory TLE associated with unilateral hippocampal sclerosis (HS). Patients were exposed to movie clips of everyday events prior to scanning, which they subsequently recalled during high-resolution fMRI. MTL structures were delineated and pattern classifiers were trained to learn the patterns of brain activity across voxels associated with each memory. Predictable patterns of activity across voxels associated with specific memories could be detected in MTL structures, including the hippocampus, on the side contralateral to the HS, indicating their functional viability. By contrast, no discernible memory representations were apparent in the sclerotic hippocampus, but adjacent MTL regions contained detectable information about the memories. These findings suggest that MVPA in fMRI memory studies of TLE can indicate hippocampal functional reserve and may be useful to predict the effects of hippocampal resection in individual patients.

19 Article Neural correlates of working memory in Temporal Lobe Epilepsy--an fMRI study. 2012

Stretton, J / Winston, G / Sidhu, M / Centeno, M / Vollmar, C / Bonelli, S / Symms, M / Koepp, M / Duncan, J S / Thompson, P J. ·Epilepsy Society MRI Unit, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK. j.stretton@ucl.ac.uk ·Neuroimage · Pubmed #22330313.

ABSTRACT: It has traditionally been held that the hippocampus is not part of the neural substrate of working memory (WM), and that WM is preserved in Temporal Lobe Epilepsy (TLE). Recent imaging and neuropsychological data suggest this view may need revision. The aim of this study was to investigate the neural correlates of WM in TLE using functional MRI (fMRI). We used a visuo-spatial 'n-back' paradigm to compare WM network activity in 38 unilateral hippocampal sclerosis (HS) patients (19 left) and 15 healthy controls. WM performance was impaired in both left and right HS groups compared to controls. The TLE groups showed reduced right superior parietal lobe activity during single- and multiple-item WM. No significant hippocampal activation was found during the active task in any group, but the hippocampi progressively deactivated as the task demand increased. This effect was bilateral for controls, whereas the TLE patients showed progressive unilateral deactivation only contralateral to the side of the hippocampal sclerosis and seizure focus. Progressive deactivation of the posterior medial temporal lobe was associated with better performance in all groups. Our results suggest that WM is impaired in unilateral HS and the underlying neural correlates of WM are disrupted. Our findings suggest that hippocampal activity is progressively suppressed as the WM load increases, with maintenance of good performance. Implications for understanding the role of the hippocampus in WM are discussed.