Atypical connectome topography and signal flow in temporal lobe epilepsy.

effectivity connectivity gradient memory multi-site multimodal temporal lobe epilepsy

Journal

Progress in neurobiology
ISSN: 1873-5118
Titre abrégé: Prog Neurobiol
Pays: England
ID NLM: 0370121

Informations de publication

Date de publication:
09 Apr 2024
Historique:
received: 26 06 2023
revised: 18 12 2023
accepted: 07 04 2024
medline: 12 4 2024
pubmed: 12 4 2024
entrez: 11 4 2024
Statut: aheadofprint

Résumé

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 patients and 40 controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Identifiants

DOI: 10.1016/j.pneurobio.2024.102604 PMID: 38604584
pubmed: 38604584
pii: S0301-0082(24)00040-6
doi: 10.1016/j.pneurobio.2024.102604
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102604

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors report no competing interests.

Auteurs

Ke Xie (K)

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

Jessica Royer (J)

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

Sara Larivière (S)

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

Raul Rodriguez-Cruces (R)

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

Stefan Frässle (S)

Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.

Donna Gift Cabalo (DG)

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

Alexander Ngo (A)

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

Jordan DeKraker (J)

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

Hans Auer (H)

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

Shahin Tavakol (S)

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

Yifei Weng (Y)

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Chifaou Abdallah (C)

Analytical Neurophysiology Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.

Thaera Arafat (T)

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

Linda Horwood (L)

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

Birgit Frauscher (B)

Analytical Neurophysiology Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.

Lorenzo Caciagli (L)

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Andrea Bernasconi (A)

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.

Neda Bernasconi (N)

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.

Zhiqiang Zhang (Z)

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Luis Concha (L)

Institute of Neurobiology, Universidad Nacional Autónoma de Mexico (UNAM), Queretaro, Mexico.

Boris C Bernhardt (BC)

Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada. Electronic address: boris.bernhardt@mcgill.ca.

Classifications MeSH