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Lookup NU author(s): Dr Gerard HallORCiD, Professor Peter TaylorORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2026 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. Objectives: Temporal lobe epilepsy (TLE) impacts multiple brain networks. Aberrant functional connectivity has been demonstrated in resting-state networks (RSNs) that mediate higher brain functions in TLE. This study aimed to identify the reproducible patterns of altered functional connectivity in TLE in a large, international cohort through ENIGMA-Epilepsy. Methods: Resting-state functional MRI datasets from nine centers across North America, South America, Europe and South Africa, including 442 people with TLE and 387 healthy adults, were analyzed. We examined group differences in whole-brain connectivity in patients compared to controls in seven major RSNs. We also investigated whole-brain connectivity maps for key nodes within the default mode network (DMN). Furthermore, the associations between connectivity patterns and clinical variables were assessed. Results: We found lower within-network connectivity scores (13.6% on average) and higher between-network connectivity scores (129% on average) in non-limbic RSN in TLE. This pattern was reproducible across all seven sites and most robust for DMN and visual networks. Patterns of connectivity were not associated with age of seizure onset or disease duration and were mostly similar in patients with left and right TLE with a few exceptions; isolated regions of high connectivity in left TLE and lower connectivity in right TLE compared to controls. Significance: We show strong evidence of lower connectivity within most RSNs and higher connectivity outside of these networks that was highly consistent across geographically diverse sites, demonstrating the robustness and generalizability of our findings. The findings demonstrate a consistent disruption of network organization in TLE that may underlie cognitive co-morbidities and seizure propagation patterns observed in this patient population. Plain Language Summary: In this international ENIGMA-Epilepsy study, resting-state fMRI data from 442 individuals with TLE showed reduced connectivity within major resting-state networks (about 14% lower) and markedly increased connectivity between networks (about 129% higher), compared to 387 healthy controls. These patterns were highly reproducible across sites. Connectivity alterations were not related to age of onset or disease duration and were largely similar across left and right TLE, aside from small, region-specific differences. Overall, the study demonstrates a robust, widespread reorganization of brain network connectivity in TLE, which may help explain associated cognitive difficulties and seizure spread.
Author(s): Ives-Deliperi V, Ipser J, Butler JT, Pardoe H, Soltanian-Zadeh H, Rummel C, Wiest R, Keller SS, Kreilkamp BAK, Vaudano AE, Ballerini A, Meletti S, Hall G, Taylor P, Concha L, Fajardo-Valdez A, Casseb RF, Cendes F, Yasuda CL, Lemieux L, Duncan JS, Davoodi-Bodj E, Devinsky O, Thomopoulos SI, Stein DJ, Thompson PM, Sisodiya SM, Gholipour T, McDonald CR
Publication type: Article
Publication status: Published
Journal: Epilepsia Open
Year: 2026
Pages: Epub ahead of print
Online publication date: 25/03/2026
Acceptance date: 14/12/2025
Date deposited: 13/04/2026
ISSN (print): 2470-9239
ISSN (electronic): 2470-9239
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/epi4.70209
DOI: 10.1002/epi4.70209
Data Access Statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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