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Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression.pdf (4.5 MB)

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

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posted on 2023-11-15, 16:54 authored by Sara Larivière, Saud Alhusaini, Colin P Doherty, Gianpiero CavalleriGianpiero Cavalleri, Norman DelantyNorman Delanty, Christopher D Whelan, Boris C Bernhardt
Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Funding

NIH Big Data to Knowledge (BD2K) program under consortium grant U54 EB020403)

The Allen Human Brain Atlas and the abagen toolbox (https://abagen.readthedocs.io/)

Fonds de la Recherche du Québec—Santé (FRQ-S)

Ann and Richard Sievers Neurosciene Award

Canadian Open Neuroscience Platform (CONP) fellowship

CIHR

Medical Research Council (G080212 and MR/M00841X/1)

Berkeley Fellowship jointly awarded by UCL and Gonville and Caius College, Cambridge

Biogen Inc

Brain Research UK (award 14181)

UNAM-DGAPA (IB201712, IG200117)

Conacyt (181508 and Programa de Laboratorios Nacionales)

UK Medical Research Council grant MR/K013998/1

São Paulo Research Foundation (FAPESP), Grant # 2013/07559-3 (BRAINN—Brazilian Institute of Neuroscience and Neurotechnology)

Ministry of Health (MOH), grant # NET-2013-02355313

R01 NS106957

P41 EB015922

ENIGMA-R21 (NIH/NINDS R21NS107739)

R01 (NIH/NINDS R01 NS122827)

Epilepsy Society, UK

National Science and Engineering Research Council of Canada (NSERC Discovery-1304413)

CIHR (FDN-154298, PJT-174995)

SickKids Foundation (NI17-039)

Azrieli Center for Autism Research (ACAR-TACC)

BrainCanada

Tier-2 Canada Research Chairs program

Canadian Institutes of Health Research (CIHR)

History

Data Availability Statement

Neuroimaging (ENIGMA-Epilepsy meta-analysis of summary statistics39) and transcriptomic data35 related to this paper are freely available for download (https://github.com/MICA-MNI/ENIGMA). All codes needed to analyze the data is openly available in the ENIGMA Toolbox (https://github.com/MICA-MNI/ENIGMA)110 and is complemented with an expandable online documentation (https://enigma-toolbox.readthedocs.io/).

Comments

The original article is available at https://www.nature.com/

Published Citation

Larivière S. et al. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression. Nat Commun. 2022 ;13(1):4320

Publication Date

27 July 2022

PubMed ID

35896547

Department/Unit

  • Beaumont Hospital
  • FutureNeuro Centre
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Springer Science and Business Media LLC

Version

  • Published Version (Version of Record)