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Aberrant functional connectivity has been demonstrated in resting\u2010state 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\u2010Epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Resting\u2010state 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\u2010brain connectivity in patients compared to controls in seven major RSNs. We also investigated whole\u2010brain connectivity maps for key nodes within the default mode network (DMN). Furthermore, the associations between connectivity patterns and clinical variables were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found lower within\u2010network connectivity scores (13.6% on average) and higher between\u2010network connectivity scores (129% on average) in non\u2010limbic 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>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\u2010morbidities and seizure propagation patterns observed in this patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>In this international ENIGMA\u2010Epilepsy study, resting\u2010state fMRI data from 442 individuals with TLE showed reduced connectivity within major resting\u2010state 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\u2010specific 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70209","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:39:55Z","timestamp":1774478395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abnormal functional connectivity patterns in temporal lobe epilepsy\u2014An international\n                    <scp>ENIGMA<\/scp>\n                    \u2010epilepsy study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2640-249X","authenticated-orcid":false,"given":"Victoria","family":"Ives\u2010Deliperi","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Mental Health, Neuroscience Institute University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-0032","authenticated-orcid":false,"given":"Jonathan","family":"Ipser","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Mental Health, Neuroscience Institute University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1978-6894","authenticated-orcid":false,"given":"James T.","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Health Sciences University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-2167","authenticated-orcid":false,"given":"Heath","family":"Pardoe","sequence":"additional","affiliation":[{"name":"Department of Neurology, NYU Langone School of Medicine New York University  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-6856","authenticated-orcid":false,"given":"Hamid","family":"Soltanian\u2010Zadeh","sequence":"additional","affiliation":[{"name":"Radiology and Research Administration Henry Ford Health System  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2345-7938","authenticated-orcid":false,"given":"Christian","family":"Rummel","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7030-2045","authenticated-orcid":false,"given":"Roland","family":"Wiest","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5247-9795","authenticated-orcid":false,"given":"Simon S.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6881-5191","authenticated-orcid":false,"given":"Barbara A. 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