Publications by authors named "Viviane Sziklas"

14 Publications

  • Page 1 of 1

Altered communication dynamics reflect cognitive deficits in temporal lobe epilepsy.

Epilepsia 2021 Apr 11;62(4):1022-1033. Epub 2021 Mar 11.

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Objective: Although temporal lobe epilepsy (TLE) is recognized as a system-level disorder, little work has investigated pathoconnectomics from a dynamic perspective. By leveraging computational simulations that quantify patterns of information flow across the connectome, we tested the hypothesis that network communication is abnormal in this condition, studied the interplay between hippocampal- and network-level disease effects, and assessed associations with cognition.

Methods: We simulated signal spreading via a linear threshold model that temporally evolves on a structural graph derived from diffusion-weighted magnetic resonance imaging (MRI), comparing a homogeneous group of 31 patients with histologically proven hippocampal sclerosis to 31 age- and sex-matched healthy controls. We evaluated the modulatory effects of structural alterations of the neocortex and hippocampus on network dynamics. Furthermore, multivariate statistics addressed the relationship with cognitive parameters.

Results: We observed a slowing of in- and out-spreading times across multiple areas bilaterally, indexing delayed information flow, with the strongest effects in ipsilateral frontotemporal regions, thalamus, and hippocampus. Effects were markedly reduced when controlling for hippocampal volume but not cortical thickness, underscoring the central role of the hippocampus in whole-brain disease expression. Multivariate analysis associated slower spreading time in frontoparietal, limbic, default mode, and subcortical networks with impairment across tasks tapping into sensorimotor, executive, memory, and verbal abilities.

Significance: Moving beyond descriptions of static topology toward the formulation of brain dynamics, our work provides novel insight into structurally mediated network dysfunction and demonstrates that altered whole-brain communication dynamics contribute to common cognitive difficulties in TLE.
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http://dx.doi.org/10.1111/epi.16864DOI Listing
April 2021

Large-scale mGluR5 network abnormalities linked to epilepsy duration in focal cortical dysplasia.

Neuroimage Clin 2021 29;29:102552. Epub 2020 Dec 29.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. Electronic address:

To determine the extent of metabotropic glutamate receptor type 5 (mGluR5) network abnormalities associated with focal cortical dysplasia (FCD), we performed graph theoretical analysis of [C]ABP688 PET binding potentials (BP), which allows for quantification of mGluR5 availability. Undirected graphs were constructed for the entire cortex in 17 FCD patients and 33 healthy controls using inter-regional similarity of [C]ABP688 BP. We assessed group differences in network integration between healthy controls and the ipsilateral and contralateral hemispheres of FCD patients. Compared to healthy controls, FCD patients showed reduced network efficiency and reduced small-world connectivity. The mGluR5 network of FCD patients was also less resilient to targeted removal of high centrality nodes, suggesting a less integrated network organization. In highly efficient hub nodes of FCD patients, we observed a significant negative correlation between local efficiency and duration of epilepsy only in the contralateral hemisphere, suggesting that some nodes may be more vulnerable to persistent epileptic activity. Our study provides the first in vivo evidence for a widespread reduction in cortical mGluR5 network integration in FCD patients. In addition, we find that ongoing epileptic activity may alter chemoarchitectural brain organization resulting in reduced efficiency in distant regions that are essential for network integration.
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http://dx.doi.org/10.1016/j.nicl.2020.102552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787952PMC
December 2020

A connectome-based mechanistic model of focal cortical dysplasia.

Brain 2019 03;142(3):688-699

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre and Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

Neuroimaging studies have consistently shown distributed brain anomalies in epilepsy syndromes associated with a focal structural lesion, particularly mesiotemporal sclerosis. Conversely, a system-level approach to focal cortical dysplasia has been rarely considered, likely due to methodological difficulties in addressing variable location and topography. Given the known heterogeneity in focal cortical dysplasia histopathology, we hypothesized that lesional connectivity consists of subtypes with distinct structural signatures. Furthermore, in light of mounting evidence for focal anomalies impacting whole-brain systems, we postulated that patterns of focal cortical dysplasia connectivity may exert differential downstream effects on global network topology. We studied a cohort of patients with histologically verified focal cortical dysplasia type II (n = 27), and age- and sex-matched healthy controls (n = 34). We subdivided each lesion into similarly sized parcels and computed their connectivity to large-scale canonical functional networks (or communities). We then dichotomized connectivity profiles of lesional parcels into those belonging to the same functional community as the focal cortical dysplasia (intra-community) and those adhering to other communities (inter-community). Applying hierarchical clustering to community-reconfigured connectome profiles identified three lesional classes with distinct patterns of functional connectivity: decreased intra- and inter-community connectivity, a selective decrease in intra-community connectivity, and increased intra- as well as inter-community connectivity. Hypo-connectivity classes were mainly composed of focal cortical dysplasia type IIB, while the hyperconnected lesions were type IIA. With respect to whole-brain networks, patients with hypoconnected focal cortical dysplasia and marked structural damage showed only mild imbalances, while those with hyperconnected subtle lesions had more pronounced topological alterations. Correcting for interictal epileptic discharges did not impact connectivity patterns. Multivariate structural equation analysis provided a mechanistic model of such complex, diverging interactions, whereby the focal cortical dysplasia structural makeup shapes its functional connectivity, which in turn modulates whole-brain network topology.
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http://dx.doi.org/10.1093/brain/awz009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391612PMC
March 2019

Resting state executive control network adaptations in amnestic mild cognitive impairment.

J Alzheimers Dis 2014 ;40(4):993-1004

Translational Neuroimaging Laboratory, Douglas Hospital, McGill University, Montreal, QC, Canada McGill Centre for Studies in Aging (MCSA), McGill University, Montreal, QC, Canada McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, QC, Canada.

Executive dysfunction is frequently associated with episodic memory decline in amnestic mild cognitive impairment (aMCI) patients. Resting state executive control network (RS-ECN) represents a novel approach to interrogate the integrity of brain areas underlying executive dysfunction. The present study aims to investigate RS-ECN in aMCI and examine a possible link between changes in brain functional connectivity and declines in executive function. aMCI individuals (n = 13) and healthy subjects (n = 16) underwent cognitive assessment including executive function and high field functional magnetic resonance imaging. Individual RS-ECN maps were estimated using a seed-based cross-correlation method. Between groups RS-ECN functional connectivity comparison was assessed using voxel-wise statistic parametric mapping. aMCI individuals had reduced RS-ECN connectivity in the anterior cingulate cortex (ACC) and dorsal lateral prefrontal cortex (DLPFC), bilaterally. In contrast, aMCI showed increased connectivity in ventral lateral and anterior prefrontal cortex, bilaterally. Connectivity strength was associated with executive function in the ACC (r = 0.6213, p = 0.023) and right DLPFC (r = 0.6454, p = 0.017). Coexistence between connectivity declines and recruitment of brain regions outside the RS-ECN as reported here fits a brain reserve conceptual framework in which brain networks undergo remodeling in aMCI individuals.
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http://dx.doi.org/10.3233/JAD-131574DOI Listing
January 2015

White matter abnormalities and structural hippocampal disconnections in amnestic mild cognitive impairment and Alzheimer's disease.

PLoS One 2013 27;8(9):e74776. Epub 2013 Sep 27.

Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging (MCSA), McGill University, Montreal, Quebec, Canada.

The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer's disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer's disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer's disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer's group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer's disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074776PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785512PMC
August 2014

fMRI of verbal and nonverbal memory processes in healthy and epileptogenic medial temporal lobes.

Epilepsy Behav 2012 Sep 17;25(1):42-9. Epub 2012 Aug 17.

Montreal Neurological Institute, 3801 University St, Montreal, Canada QC H3A 2B4.

Material-specific memory impairments are a well-established consequence of unilateral medial temporal lobe damage. We used fMRI to investigate encoding and recognition of verbal and nonverbal stimuli using adaptations of tasks used successfully in clinical evaluations of patients with temporal lobe epilepsy (TLE). We studied two patient groups, one with left TLE and one with right TLE, and one group of healthy subjects. Results from the healthy subjects indicated that initial and delayed recognition trials of the verbal task activated the left medial temporal lobe, and the same tasks of the nonverbal task activated the right, confirming the sensitivity to laterality of our clinical tasks. Patients tended to use the opposite hippocampus, but often the parahippocampal gyrus on the same side, compared to the healthy subjects. Since our patients and the healthy groups performed similarly on the memory tasks, we conclude that the patients' activation patterns represent an effective adaptation to the presence of an unhealthy hippocampus.
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http://dx.doi.org/10.1016/j.yebeh.2012.07.003DOI Listing
September 2012

The Story Learning and Memory (SLAM) test: equivalence of three forms and sensitivity to left temporal lobe dysfunction.

Epilepsy Behav 2011 Mar 26;20(3):518-23. Epub 2011 Feb 26.

McGill University, Montreal, Quebec, Canada.

Remembering meaningful information is an important component of verbal memory. However, findings from existing story memory tests have been mixed in patients with temporal lobe epilepsy (TLE). We developed a test, the Story Learning and Memory (SLAM) test, in which a story is presented repeatedly until a performance criterion is reached, and verbatim recall is obtained only once, after a delay. In Study 1 we demonstrated a significant learning deficit in patients with left, but not right, TLE, and they were further impaired in retention of the story despite having learned it to the same criterion as subjects with right TLE and healthy subjects. These deficits remained confined to patients with left TLE after surgery. For clinical use we developed the SLAM in three versions in two languages; in studies 2 and 3 we tested and proved their equivalence.
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http://dx.doi.org/10.1016/j.yebeh.2011.01.002DOI Listing
March 2011

Awareness of deficits during intracarotid anesthetic procedures in epilepsy: Comparisons of motor, naming, and comprehension awareness under amobarbital versus under etomidate.

Epilepsy Behav 2010 Dec 5;19(4):591-5. Epub 2010 Nov 5.

Montreal Neurological Institute, Montreal, Canada.

Awareness of deficits is often impaired following disruption of the right hemisphere. Intracarotid anesthetic procedures (IAPs) represent a unique method by which we can assess functioning of each hemisphere in isolation. We used this technique to explore deficits of awareness of specific functions-motor ability, naming, and comprehension-in patients with temporal lobe epilepsy. Some patients were injected with amobarbital, whereas others were injected with etomidate. We found that injection into the right hemisphere, or epileptogenic focus in the right hemisphere following injection in the left, resulted in the lowest levels of motor awareness. We also found a higher level of awareness for expressive language deficits and less awareness for receptive language deficits. Comparison of etomidate and amobarbital suggested more awareness following injection of etomidate. We discuss how these findings contribute to our understanding of the right hemisphere's special role in awareness, and how research in other disorders and in comparative neurology has shaped our conceptualization of the neuroanatomy of insight.
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http://dx.doi.org/10.1016/j.yebeh.2010.09.020DOI Listing
December 2010

Fornix and retrosplenial contribution to a hippocampo-thalamic circuit underlying conditional learning.

Behav Brain Res 2010 May 7;209(1):13-20. Epub 2010 Jan 7.

Department of Psychology, McGill University, 1205 Dr. Penfield Ave., Montreal, Quebec, Canada H3A 1B1.

Rats with combined bilateral lesions of the retrosplenial cortex and the fornix or rats with unilateral lesions to the anterior thalamus and the hippocampus, made in opposite hemispheres (disconnection preparation), and combined with unilateral damage of the retrosplenial cortex in either hemisphere, were tested on a spatial-visual conditional learning task in which they learned arbitrary associations between stimuli and the scene in which they were embedded. All experimental groups were impaired in comparison with normal animals. The more severe deficits occurred when (1) both the fornix and the retrosplenial cortex were damaged bilaterally thus depriving the hippocampus both from subcortical interactions via the fornix and retrosplenial-mediated interactions and (2) when, in the crossed lesion preparation, the unilateral retrosplenial lesion was made in the hemisphere with the intact hippocampus, again because this lesion would be maximally disconnecting the hippocampus from functional interaction with the anterior thalamic nucleus and retrosplenial-mediated input.
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http://dx.doi.org/10.1016/j.bbr.2009.12.040DOI Listing
May 2010

Does the cingulate cortex contribute to spatial conditional associative learning in the rat?

Hippocampus 2009 Jul;19(7):612-22

Department of Psychology, McGill University, Montreal, Quebec, Canada.

Rats with lesions to the anterior or posterior (retrosplenial) region of the cingulate cortex and rats with lesions that included both the anterior and posterior cingulate cortex were tested on a visual-spatial conditional task in which they had to learn to approach one of the two objects depending on the spatial context within which they were embedded. Lesions restricted to either the anterior or the retrosplenial cingulate region did not impair learning of this task which is known to be very sensitive to the effects of hippocampal lesions. Complete lesions of the cingulate cortex gave rise to only a minor retardation in learning. In contrast, lesions to the retrosplenial cortex impaired performance on a spatial navigation task and the classic radial maze. These results suggest that the retrosplenial portion of the cingulate region forms part of a hippocampal circuit underlying learning about spatial responses. The dissociation between the effects of lesions of the cingulate region on different classes of behavior known to be associated with hippocampal function suggests that, although this neural structure does play a role in an extended hippocampal circuit underlying spatial learning, its role in such learning may be a selective one.
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http://dx.doi.org/10.1002/hipo.20539DOI Listing
July 2009

Material-specific lateralization of working memory in the medial temporal lobe.

Neuropsychologia 2009 Jan 15;47(1):112-22. Epub 2008 Aug 15.

Montreal Neurological Institute, Neuropsychology and Cognitive Neuroscience Unit, Department of Neurology and Neurosurgery, McGill University, Canada.

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging studies, which have focused primarily on visual and visuospatial WM. In the present study we investigated material-specific lateralization of WM in 96 patients with unilateral damage to MTL stemming from TLE (56 left) and 30 control subjects using a pair of matched verbal and visuospatial supraspan tasks. Patients with unilateral TLE were impaired on both verbal and visuospatial WM tasks irrespective of the affected hemisphere. Patients with unilateral right TLE showed an additional deficit for visuospatial WM capacity when contrasted with patients with left TLE, whereas patients with unilateral left TLE showed increased intrusion errors on the verbal task when compared to patients with right TLE. These findings suggest a material-specific lateralization of WM in the MTL.
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http://dx.doi.org/10.1016/j.neuropsychologia.2008.08.010DOI Listing
January 2009

RAVLT and nonverbal analog: French forms and clinical findings.

Can J Neurol Sci 2008 Jul;35(3):323-30

Montreal Neurological Institute, Department of Psychology, McGill University, Montreal, Quebec, Canada.

Background: Objective clinical evaluation of memory frequently requires serial testing but the issue of whether multi-formed tests are equivalent and can be used interchangeably is seldom examined. An added problem in bilingual Canadian settings is the extent to which it is appropriate to measure French speakers' performance on translations of English tests. The present work used the Rey Auditory Verbal Learning Test (RAVLT) and a nonverbal analog, the Aggie Figures Learning Test (AFLT), to examine whether a) different forms of the same test are equivalent, b) performance on the two tests is comparable, c) two language groups perform similarly, and d) the RAVLT can detect dysfunction in patients with temporal lobe epilepsy (TLE).

Methods: We compared three French versions of the RAVLT and three forms of the AFLT in 114 healthy francophone adults. We subsequently compared the performance of the same francophone subjects to a previously obtained sample of anglophones on both tests, and then administered the RAVLT to anglophone or francophone patients with TLE.

Results: For both tasks the three forms were equivalent and performance on the RAVLT was comparable to that on the AFLT. Francophone subjects performed slightly worse on the RAVLT compared to anglophones but performance of the two language groups did not differ on the AFLT. Finally, left TLE patients were impaired compared to right on the RAVLT, but no performance differences were observed across the two language groups in the patient sample.

Conclusions: The RAVLT and AFLT are useful tools for examination of learning and memory in French and English speaking populations. On the RAVLT, the lesion effect in patients is not affected by differences in performance between language groups.
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http://dx.doi.org/10.1017/s0317167100008908DOI Listing
July 2008

Spatial conditional associative learning: effects of thalamo-hippocampal disconnection in rats.

Neuroreport 2004 Oct;15(15):2427-31

Department of Psychology, McGill University, 1205 Dr. Penfield Ave, Montreal, Quebec, Canada H3A 1B1.

Unilateral lesions to the anterior thalamic nuclei (ATN) and the hippocampus (H) were made in opposite hemispheres in the rat to examine whether these brain structures form part of a functional neural pathway underlying spatial learning and memory. In the first experiment, rats were tested on a spatial-visual conditional associative task in which they had to learn to approach one of two stimuli depending on the spatial context in which the stimuli were embedded. The rats were subsequently trained on delayed forced alternation, a spatial working memory task known to be sensitive to the effects of ATNxH damage. Rats with ATNxH lesions were impaired in the acquisition of both tasks in comparison with normal control animals. The findings support the idea that the anterior thalamic nuclei and the hippocampus are critical components of an anatomical system subserving spatial memory and suggest that these brain regions work in a dependent fashion during the performance of certain spatial learning tasks.
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http://dx.doi.org/10.1097/00001756-200410250-00025DOI Listing
October 2004

The effects of adjunctive topiramate on cognitive function in patients with epilepsy.

Epilepsia 2003 Mar;44(3):339-47

McGill University, Montreal Neurological Hospital, Montreal, Quebec, Canada.

Purpose: We investigated possible cognitive effects of topiramate (TPM) in polypharmacy on patients with intractable epilepsy.

Methods: Study 1 evaluated 22 consecutively admitted patients whose antiepileptic drugs (AEDs) on admission to the Montreal Neurological Hospital included TPM. Performance on neuropsychological tests administered on and subsequently off TPM was analyzed. Four patients also were tested before taking TPM, allowing comparisons off, then on, and then off the drug again. Measures included intellectual function, verbal and nonverbal memory, language, word and design fluency, somatosensory sensitivity, and motor skills. In Study 2, 16 patients at the Minnesota Epilepsy Group were tested first off, then on TPM with nine cognitive tasks that measured concentration, verbal fluency, language, and psychomotor speed.

Results: In Study 1, significant (p < or = 0.01) improvements were observed off TPM on 13 measures including verbal and nonverbal fluency and certain verbal and perceptual tasks. Notably, verbal learning and memory were unaffected; a limited effect was observed on nonverbal memory. Patients tested 3 times scored better in both tests off TPM compared with on this drug. In Study 2, declines on TPM were observed on all measures, significantly (p < or = 0.05) for tests of fluency, sustained concentration, and visual motor processing speed.

Conclusions: TPM was associated with declines in fluency, attention/concentration, processing speed, language skills, and perception; working memory but not retention was affected. As the two studies used an opposite order of testing on versus off TPM, our results clearly show a performance decrement while patients are taking TPM, without respect to which condition is tested first.
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http://dx.doi.org/10.1046/j.1528-1157.2003.27402.xDOI Listing
March 2003