Publications by authors named "Benoit Caldairou"

16 Publications

  • Page 1 of 1

Atypical neural topographies underpin dysfunctional pattern separation in temporal lobe epilepsy.

Brain 2021 Mar 17. Epub 2021 Mar 17.

Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.

Episodic memory is the ability to accurately remember events from our past. The process of pattern separation is hypothesized to underpin this ability and is defined as the ability to orthogonalize memory traces, to maximize the features that make them unique. Contemporary cognitive neuroscience suggests that pattern separation entails complex interactions between the hippocampus and the neocortex, where specific hippocampal subregions shape neural reinstatement in the neocortex. To test this hypothesis, the current work studied both healthy controls and patients with temporal lobe epilepsy (TLE) who present with hippocampal structural anomalies. In all participants, we measured neural activity using functional magnetic resonance imaging (fMRI) while they retrieved memorized items compared to lure items which share features with the target. Behaviorally, TLE patients were less able to exclude lures than controls, and showed a reduction in pattern separation. To assess the hypothesized relationship between neural patterns in the hippocampus and the neocortex, we identified topographic gradients of intrinsic connectivity along neocortical and hippocampal subfield surfaces and identified the topographic profile of the neural activity accompanying pattern separation. In healthy controls, pattern separation followed a graded pattern of neural activity, both along the hippocampal long axis (and peaked in anterior segments that are more heavily engaged in transmodal processing) and along the neocortical hierarchy running from unimodal to transmodal regions (peaking in transmodal default mode regions). In TLE patients, however, this concordance between task-based functional activations and topographic gradients was markedly reduced. Furthermore, person specific measures of concordance between task-related activity and connectivity gradients in patients and controls related to inter-individual differences in behavioral measures of pattern separation and episodic memory, highlighting the functional relevance of the observed topographic motifs. Our work is consistent with an emerging understanding that successful discrimination between memories with similar features entails a shift in the locus of neural activity away from sensory systems, a pattern that is mirrored along the hippocampal long axis and with respect to neocortical hierarchies. More broadly, our study establishes topographic profiling using intrinsic connectivity gradients captures the functional underpinnings of episodic memory processes in manner that is sensitive to their reorganization in pathology.
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http://dx.doi.org/10.1093/brain/awab121DOI Listing
March 2021

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

Whole-brain multimodal MRI phenotyping of periventricular nodular heterotopia.

Neurology 2020 10 14;95(17):e2418-e2426. Epub 2020 Aug 14.

From the Neuroimaging of Epilepsy Laboratory (F.D., S.-J.H., F.F., B.C., S.K., N.B., A.B.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; and Epilepsy Unit (F.D.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Objective: To test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and function of cortical areas overlying the heterotopic gray matter are preferentially affected.

Methods: We studied a group of 40 patients with PVNH and normal-appearing cortex and compared their quantitative MRI markers of brain development, structure, and function to those of 43 age- and sex-matched healthy controls. Inspired by models of neocortical development suggesting that neuronal migration follows a curvilinear path to preserve topologic correspondence between the outer ventricular zone and the cortical surface, we computationally defined the overlying cortex using the Laplace equation and generated synthetic streamlines that link the ventricles, where nodules are located, and the neocortex.

Results: We found multilobar cortical thickening encompassing prefrontal, latero-basal temporal, and temporoparietal cortices largely corresponding with the PVNH group-averaged map of the overlying cortex, the latter colocalized with areas of abnormal function, as defined by resting-state fMRI. Patients also presented hippocampal functional hyperconnectivity and malrotation, the latter positively correlating with neocortical maldevelopment indexed by increased folding complexity of the parahippocampus. In clusters of thickness and curvature findings, there were no significant differences between unilateral and bilateral PVNH; contrasting brain-wide metrics between cohorts was also unrevealing. There was no relationship between imaging markers and disease duration except for positive correlation with functional anomalies.

Conclusion: Our quantitative image analysis demonstrates widespread structural and functional alterations in PVNH with differential interaction with the overlying cortex and the hippocampus. Right hemispheric predominance may be explained by an early insult, likely genetically determined, on brain morphogenesis.
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http://dx.doi.org/10.1212/WNL.0000000000010648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682914PMC
October 2020

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study.

Brain 2020 08;143(8):2454-2473

Department of Neurology, Medical University of South Carolina, Charleston 29425 SC, USA.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
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http://dx.doi.org/10.1093/brain/awaa200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567169PMC
August 2020

The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Hum Brain Mapp 2020 May 29. Epub 2020 May 29.

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.
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http://dx.doi.org/10.1002/hbm.25037DOI Listing
May 2020

Microstructural imaging in temporal lobe epilepsy: Diffusion imaging changes relate to reduced neurite density.

Neuroimage Clin 2020 28;26:102231. Epub 2020 Feb 28.

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, UK.

Purpose: Previous imaging studies in patients with refractory temporal lobe epilepsy (TLE) have examined the spatial distribution of changes in imaging parameters such as diffusion tensor imaging (DTI) metrics and cortical thickness. Multi-compartment models offer greater specificity with parameters more directly related to known changes in TLE such as altered neuronal density and myelination. We studied the spatial distribution of conventional and novel metrics including neurite density derived from NODDI (Neurite Orientation Dispersion and Density Imaging) and myelin water fraction (MWF) derived from mcDESPOT (Multi-Compartment Driven Equilibrium Single Pulse Observation of T1/T2)] to infer the underlying neurobiology of changes in conventional metrics.

Methods: 20 patients with TLE and 20 matched controls underwent magnetic resonance imaging including a volumetric T1-weighted sequence, multi-shell diffusion from which DTI and NODDI metrics were derived and a protocol suitable for mcDESPOT fitting. Models of the grey matter-white matter and grey matter-CSF surfaces were automatically generated from the T1-weighted MRI. Conventional diffusion and novel metrics of neurite density and MWF were sampled from intracortical grey matter and subcortical white matter surfaces and cortical thickness was measured.

Results: In intracortical grey matter, diffusivity was increased in the ipsilateral temporal and frontopolar cortices with more restricted areas of reduced neurite density. Diffusivity increases were largely related to reductions in neurite density, and to a lesser extent CSF partial volume effects, but not MWF. In subcortical white matter, widespread bilateral reductions in fractional anisotropy and increases in radial diffusivity were seen. These were primarily related to reduced neurite density, with an additional relationship to reduced MWF in the temporal pole and anterolateral temporal neocortex. Changes were greater with increasing epilepsy duration. Bilaterally reduced cortical thickness in the mesial temporal lobe and centroparietal cortices was unrelated to neurite density and MWF.

Conclusions: Diffusivity changes in grey and white matter are primarily related to reduced neurite density with an additional relationship to reduced MWF in the temporal pole. Neurite density may represent a more sensitive and specific biomarker of progressive neuronal damage in refractory TLE that deserves further study.
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http://dx.doi.org/10.1016/j.nicl.2020.102231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063236PMC
February 2021

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling.

Hum Brain Mapp 2019 12 24;40(18):5213-5230. Epub 2019 Aug 24.

Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n = 102, age range = 30-89 years) with MRI and Aβ PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface-based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced toward higher-order transmodal regions. Age-related atrophy was greater toward the posterior end of the hippocampal long-axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography-specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain-based biomarkers of aging.
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http://dx.doi.org/10.1002/hbm.24767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864903PMC
December 2019

Temporal lobe epilepsy: Hippocampal pathology modulates connectome topology and controllability.

Neurology 2019 05 19;92(19):e2209-e2220. Epub 2019 Apr 19.

From the Neuroimaging of Epilepsy Laboratory (B.C.B., F.F., M.L., B.C., A.B., N.B.) and Multimodal Imaging and Connectome Analysis Laboratory (B.C.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Canada; Department of Bioengineering and Electrical and Systems Engineering (S.G., D.S.B.), University of Pennsylvania, Philadelphia; and York Neuroimaging Center (E.J., J.S.), University of York, UK.

Objective: To assess whether hippocampal sclerosis (HS) severity is mirrored at the level of large-scale networks.

Methods: We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 temporal lobe epilepsy (TLE) patients with histopathologic diagnosis of HS (n = 25; TLE-HS) and isolated gliosis (n = 19; TLE-G) and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm that simulates functional dynamics from structural network data.

Results: Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from gray matter atrophy.

Conclusions: Severe HS is associated with marked remodeling of connectome topology and structurally governed functional dynamics in TLE, as opposed to isolated gliosis, which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales.
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http://dx.doi.org/10.1212/WNL.0000000000007447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537128PMC
May 2019

Anatomical and microstructural determinants of hippocampal subfield functional connectome embedding.

Proc Natl Acad Sci U S A 2018 10 24;115(40):10154-10159. Epub 2018 Sep 24.

Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada;

The hippocampus plays key roles in cognition and affect and serves as a model system for structure/function studies in animals. So far, its complex anatomy has challenged investigations targeting its substructural organization in humans. State-of-the-art MRI offers the resolution and versatility to identify hippocampal subfields, assess its microstructure, and study topographical principles of its connectivity in vivo. We developed an approach to unfold the human hippocampus and examine spatial variations of intrinsic functional connectivity in a large cohort of healthy adults. In addition to mapping common and unique connections across subfields, we identified two main axes of subregional connectivity transitions. An anterior/posterior gradient followed long-axis landmarks and metaanalytical findings from task-based functional MRI, while a medial/lateral gradient followed hippocampal infolding and correlated with proxies of cortical myelin. Findings were consistent in an independent sample and highly stable across resting-state scans. Our results provide robust evidence for long-axis specialization in the resting human hippocampus and suggest an intriguing interplay between connectivity and microstructure.
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http://dx.doi.org/10.1073/pnas.1803667115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176604PMC
October 2018

Multi-Template Mesiotemporal Lobe Segmentation: Effects of Surface and Volume Feature Modeling.

Front Neuroinform 2018 12;12:39. Epub 2018 Jul 12.

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

Numerous neurological disorders are associated with atrophy of mesiotemporal lobe structures, including the hippocampus (HP), amygdala (AM), and entorhinal cortex (EC). Accurate segmentation of these structures is, therefore, necessary for understanding the disease process and patient management. Recent multiple-template segmentation algorithms have shown excellent performance in HP segmentation. Purely surface-based methods precisely describe structural boundary but their performance likely depends on a large template library, as segmentation suffers when the boundaries of template and individual MRI are not well aligned while volume-based methods are less dependent. So far only few algorithms attempted segmentation of entire mesiotemporal structures including the parahippocampus. We compared performance of surface- and volume-based approaches in segmenting the three mesiotemporal structures and assess the effects of different environments (i.e., size of templates, under pathology). We also proposed an algorithm that combined surface- with volume-derived similarity measures for optimal template selection. To further improve the method, we introduced two new modules: (1) a non-linear registration that is driven by volume-based intensities and features sampled on deformable template surfaces; (2) a shape averaging based on regional weighting using multi-scale global-to-local icosahedron sampling. Compared to manual segmentations, our approach, namely showed high accuracy in 40 healthy controls (mean Dice index for HP/AM/EC = 89.7/89.3/82.9%) and 135 patients with temporal lobe epilepsy (88.7/89.0/82.6%). This accuracy was comparable across two different datasets of 1.5T and 3T MRI. It resulted in the best performance among tested multi-template methods that were either based on volume or surface data alone in terms of accuracy and sensitivity to detect atrophy related to epilepsy. Moreover, unlike purely surface-based multi-template segmentation, could maintain accurate performance even with a 50% template library size.
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http://dx.doi.org/10.3389/fninf.2018.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052096PMC
July 2018

Multimodal MRI profiling of focal cortical dysplasia type II.

Neurology 2017 Feb 27;88(8):734-742. Epub 2017 Jan 27.

From the Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital (S.-J.H., B.C.B., B.C., J.A.H., M.C.G., N.B., A.B.), Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre (S.-J.H., B.C.B., B.C., D.S., N.B., A.B.), and Department of Pathology (M.C.G.), McGill University, Montreal, Canada.

Objective: To characterize in vivo MRI signatures of focal cortical dysplasia (FCD) type IIA and type IIB through combined analysis of morphology, intensity, microstructure, and function.

Methods: We carried out a multimodal 3T MRI profiling of 33 histologically proven FCD type IIA (9) and IIB (24) lesions. A multisurface approach operating on manual consensus labels systematically sampled intracortical and subcortical lesional features. Geodesic distance mapping quantified the same features in the lesion perimeter. Logistic regression assessed the relationship between MRI and histology, while supervised pattern learning was used for individualized subtype prediction.

Results: FCD type IIB was characterized by abnormal morphology, intensity, diffusivity, and function across all surfaces, while type IIA lesions presented only with increased fluid-attenuated inversion recovery signal and reduced diffusion anisotropy close to the gray-white matter interface. Similar to lesional patterns, perilesional anomalies were more marked in type IIB extending up to 16 mm. Structural MRI markers correlated with categorical histologic characteristics. A profile-based classifier predicted FCD subtypes with equal sensitivity of 85%, while maintaining a high specificity of 94% against healthy and disease controls.

Conclusions: Image processing applied to widely available MRI contrasts has the ability to dissociate FCD subtypes at a mesoscopic level. Integrating in vivo staging of pathologic traits with automated lesion detection is likely to provide an objective definition of lesional boundary and assist emerging approaches, such as minimally invasive thermal ablation, which do not supply tissue specimen.
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http://dx.doi.org/10.1212/WNL.0000000000003632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344077PMC
February 2017

The superficial white matter in temporal lobe epilepsy: a key link between structural and functional network disruptions.

Brain 2016 09 29;139(Pt 9):2431-40. Epub 2016 Jun 29.

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

Drug-resistant temporal lobe epilepsy is increasingly recognized as a system-level disorder affecting the structure and function of large-scale grey matter networks. While diffusion magnetic resonance imaging studies have demonstrated deep fibre tract alterations, the superficial white matter immediately below the cortex has so far been neglected despite its proximity to neocortical regions and key role in maintaining cortico-cortical connectivity. Using multi-modal 3 T magnetic resonance imaging, we mapped the topography of superficial white matter diffusion alterations in 61 consecutive temporal lobe epilepsy patients relative to 38 healthy controls and studied the relationship to large-scale structural as well as functional networks. Our approach continuously sampled mean diffusivity and fractional anisotropy along surfaces running 2 mm below the cortex. Multivariate statistics mapped superficial white matter diffusion anomalies in patients relative to controls, while correlation and mediation analyses evaluated their relationship to structural (cortical thickness, mesiotemporal volumetry) and functional parameters (resting state functional magnetic resonance imaging amplitude) and clinical variables. Patients presented with overlapping anomalies in mean diffusivity and anisotropy, particularly in ipsilateral temporo-limbic regions. Diffusion anomalies did not relate to cortical thinning; conversely, they mediated large-scale functional amplitude decreases in patients relative to controls in default mode hub regions (i.e. anterior and posterior midline regions, lateral temporo-parietal cortices), and were themselves mediated by hippocampal atrophy. With respect to clinical variables, we observed more marked diffusion anomalies in patients with a history of febrile convulsions and those with longer disease duration. Similarly, more marked diffusion alterations were associated with seizure-free outcome. Bootstrap analyses indicated high reproducibility of our findings, suggesting generalizability. The temporo-limbic distribution of superficial white matter anomalies, together with the mediation-level findings, suggests that this so far neglected region serves a key link between the hippocampal atrophy and large-scale default mode network alterations in temporal lobe epilepsy.
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http://dx.doi.org/10.1093/brain/aww167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995361PMC
September 2016

The spectrum of structural and functional imaging abnormalities in temporal lobe epilepsy.

Ann Neurol 2016 07 9;80(1):142-53. Epub 2016 Jun 9.

From the Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

Objective: Although most temporal lobe epilepsy (TLE) patients show marked hippocampal sclerosis (HS) upon pathological examination, 40% present with no significant cell loss but gliotic changes only. To evaluate effects of hippocampal pathology on brain structure and functional networks, we aimed at dissociating multimodal magnetic resonance imaging (MRI) characteristics in patients with HS (TLE-HS) and those with gliosis only (TLE-G).

Methods: In 20 TLE-HS, 19 TLE-G, and 25 healthy controls, we carried out a novel MRI-based hippocampal subfield surface analysis that integrated volume, T2 signal intensity, and diffusion markers with seed-based hippocampal functional connectivity.

Results: Compared to controls, TLE-HS presented with marked ipsilateral atrophy, T2 hyperintensity, and mean diffusivity increases across all subfields, whereas TLE-G presented with dentate gyrus hypertrophy, focal increases in T2 intensity and mean diffusivity. Multivariate assessment confirmed a more marked ipsilateral load of anomalies across all subfields in TLE-HS, whereas anomalies in TLE-G were restricted to the subiculum. A between-cohort dissociation was independently suggested by resting-state functional connectivity analysis, revealing marked hippocampal decoupling from anterior and posterior default mode hubs in TLE-HS, whereas TLE-G did not differ from controls. Back-projection connectivity analysis from cortical targets revealed consistently decreased network embedding across all subfields in TLE-HS, while changes in TLE-G were limited to the subiculum. Hippocampal disconnectivity strongly correlated to T2 hyperintensity and marginally to atrophy.

Interpretation: Multimodal MRI reveals diverging structural and functional connectivity profiles across the TLE spectrum. Pathology-specific modulations of large-scale functional brain networks lend novel evidence for a close interplay of structural and functional disruptions in focal epilepsy. Ann Neurol 2016;80:142-153.
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http://dx.doi.org/10.1002/ana.24691DOI Listing
July 2016

Interictal Hippocampal Spiking Influences the Occurrence of Hippocampal Sleep Spindles.

Sleep 2015 Dec 1;38(12):1927-33. Epub 2015 Dec 1.

Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada.

Objectives: The significance of hippocampal sleep spindles and their relation to epileptic activity is still a matter of controversy. Hippocampal spindles have been considered a physiological phenomenon, an evoked response to afferent epileptic discharges, or even the expression of an epileptic manifestation. To address this question, we investigated the presence and rate of hippocampal spindles in focal pharmacoresistant epilepsy patients undergoing scalp-intracerebral electroencephalography (EEG).

Design: Sleep recording with scalp-intracerebral EEG.

Setting: Tertiary referral epilepsy center.

Patients: Twenty-five epilepsy patients (extratemporal: n = 6, temporal: n = 15, and multifocal including the temporal lobe: n = 4).

Interventions: N/A.

Measurements And Results: We analyzed associations between hippocampal spindles and hippocampal electrophysiological findings (interictal spiking, seizure onset zone) and magnetic resonance imaging volumetry. Sixteen of 25 patients (64%) had hippocampal spindles (extratemporal epilepsy: 6/6; temporal epilepsy: 10/15; and multifocal epilepsy: 0/4; P = 0.005). Median spindle rate was 0.6 (range, 0.1-8.6)/min in nonrapid eye movement sleep. Highest spindle rates were found in hippocampi of patients with extratemporal epilepsy (P < 0.001). A negative association was found between hippocampal spiking activity and spindle rate (P = 0.003). We found no association between the presence (n = 21) or absence (n = 17) of hippocampal seizure onset zone and hippocampal spindle rate (P = 0.114), and between a normal (n = 30) or atrophic (n = 8) hippocampus and hippocampal spindle rate (P = 0.195).

Conclusions: Hippocampal spindles represent a physiological phenomenon, with an expression that is diminished in epilepsy affecting the temporal lobe. Hippocampal spiking lowered the rate of hippocampal spindles, suggesting that epileptic discharges may at least in part be a transformation of these physiological events, similar to the hypothesis considering generalized spike-and-waves a transformation of frontal spindles.
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http://dx.doi.org/10.5665/sleep.5242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667386PMC
December 2015

Accurate cortical tissue classification on MRI by modeling cortical folding patterns.

Hum Brain Mapp 2015 Sep 3;36(9):3563-74. Epub 2015 Jun 3.

Department of Neurology and Neurosurgery, Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

Accurate tissue classification is a crucial prerequisite to MRI morphometry. Automated methods based on intensity histograms constructed from the entire volume are challenged by regional intensity variations due to local radiofrequency artifacts as well as disparities in tissue composition, laminar architecture and folding patterns. Current work proposes a novel anatomy-driven method in which parcels conforming cortical folding were regionally extracted from the brain. Each parcel is subsequently classified using nonparametric mean shift clustering. Evaluation was carried out on manually labeled images from two datasets acquired at 3.0 Tesla (n = 15) and 1.5 Tesla (n = 20). In both datasets, we observed high tissue classification accuracy of the proposed method (Dice index >97.6% at 3.0 Tesla, and >89.2% at 1.5 Tesla). Moreover, our method consistently outperformed state-of-the-art classification routines available in SPM8 and FSL-FAST, as well as a recently proposed local classifier that partitions the brain into cubes. Contour-based analyses localized more accurate white matter-gray matter (GM) interface classification of the proposed framework compared to the other algorithms, particularly in central and occipital cortices that generally display bright GM due to their highly degree of myelination. Excellent accuracy was maintained, even in the absence of correction for intensity inhomogeneity. The presented anatomy-driven local classification algorithm may significantly improve cortical boundary definition, with possible benefits for morphometric inference and biomarker discovery.
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http://dx.doi.org/10.1002/hbm.22862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869288PMC
September 2015

Multivariate hippocampal subfield analysis of local MRI intensity and volume: application to temporal lobe epilepsy.

Med Image Comput Comput Assist Interv 2014 ;17(Pt 2):170-8

We propose a multispectral MRI-based clinical decision support approach to carry out automated seizure focus lateralization in patients with temporal lobe epilepsy (TLE). Based on high-resolution T1- and T2-weighted MRI with hippocampal subfield segmentations, our approach samples MRI features along the medial sheet of each subfield to minimize partial volume effects. To establish correspondence of sampling points across subjects, we propagate a spherical harmonic parameterization derived from the hippocampal boundary along a Laplacian gradient field towards the medial sheet. Volume and intensity data sampled on the medial sheet are finally fed into a supervised classifier. Testing our approach in TLE patients in whom the seizure focus could not be lateralized using conventional MR volumetry, the proposed approach correctly lateralized all patients and outperformed classification performance based on global subfield volumes or mean T2-intensity (100% vs. 68%). Moreover, statistical group-level comparisons revealed patterns of subfield abnormalities that were not evident in the global measurements and that largely agree with known histopathological changes.
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http://dx.doi.org/10.1007/978-3-319-10470-6_22DOI Listing
January 2015