Objectives: Temporal lobe epilepsy (TLE) involves 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 reproducible patterns of altered functional connectivity in TLE in a large, international cohort through ENIGMA-Epilepsy.
Methods: Resting-state functional MRI datasets from eight centres across North American, South America, Europe and South Africa, including 442 people with TLE and 387 healthy adults, were analysed. 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). Further, 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 highly reproducible across sites and most robust for DMN and visual networks. Patterns of connectivity were not associated with age of seizure onset or disease duration but differed between left and right TLE; higher connectivity was observed in left TLE and lower connectivity in right TLE.
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.
Note:
Funding declaration: NIH/NINDS R01NS122827 (CRM, SMS, HP and PT). CONAHCYT 181508, 1782, CF-2023-218, and UNAM-DGAPA IN213423, IB201712, IG200117. SMS was supported by the Epilepsy Society ORCID: https://orcid.org/0000-0003-2640-249X.
Conflict of Interests: None.
Ethical Approval: Ethics approval to contribute data to the study was obtained from each centre’s review board and the combined analyses of the data was approved by the Human Research Ethics Committee at the University of Cape Town, South Africa.
Keywords: Temporal lobe epilepsy, functional MRI, resting state functional connectivity
Ives-Deliperi, Victoria and Ipser, Jonathan and Butler, James T. and Pardoe, Heath and Soltanian-Zadeh, Hamid and Rummel, Christian and Wiest, Roland and Keller, Simon S. and Kreilkamp, Barbara A.K. and Vaudano, Anna Elisabetta and Ballerini, Alice and Meletti, Stefano and Hall, Gerard and Taylor, Peter and Concha, Luis and Fajardo-Valdez, Alfonso and Casseb, Raphael Fernandes and Cendes, Fernando and Yasuda, Clarissa L. and Lemieux, Louis and Duncan, John and Davoodi-Bodj, Esmaeil and Devinsky, Orrin and Thomopoulos, Sophia I. and Stein, Dan J. and Thompson, Paul M. and Sisodiya, Sanjay M. and Gholipour, Taha and McDonald, Carrie R., Abnormal Functional Connectivity Patterns in Temporal Lobe Epilepsy – An International ENIGMA-Epilepsy Study. Available at SSRN: https://ssrn.com/abstract=5229531 or http://dx.doi.org/10.2139/ssrn.5229531
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