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Functional magnetic\u00a0resonance\u00a0imaging data were acquired during a Chinese version of the verbal fluency task. The patients were followed up until the outcome could be classified. The subject groups were compared in terms of activation profile, task\u2010residual functional connectivity (trFC), and generalized psychophysiological interaction (gPPI) analyses. Moreover, we extracted imaging characteristics for logistic regression and receiver operating characteristic evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With a mean follow\u2010up of 1.1\u00a0years, we identified 27 non\u2010seizure\u2010free patients and 19\u00a0seizure\u2010free patients in the final analyses. The Chinese character verbal fluency task successfully activated the language network and cognitive control network (CCN) and deactivated the default mode network (DMN). In the non\u2010seizure\u2010freedom group, the trFC between the hippocampus and bilateral brain networks was attenuated (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05, familywise error corrected). For the gPPI analysis, group differences were mainly located in the precuneus, middle frontal gyrus, and inferior parietal lobule (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001, uncorrected; <jats:italic>k<\/jats:italic> \u2265 10). The regression model presented high accuracy when predicting non\u2010seizure\u2010free patients (area under the curve = .879, 95% confidence interval = .761\u2013.998).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>In patients with TLE who would not achieve seizure freedom with current antiseizure medications, the functional connectivity between the hippocampus and central nodes of the DMN, CCN, and language network was disrupted, leading to language decline. Independent of hippocampal sclerosis, abnormalities, especially the effective connectivity from the hippocampus to the DMN, were predictive biomarkers of drug responsiveness in patients with TLE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17142","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T11:53:40Z","timestamp":1638878020000},"page":"463-473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Abnormal functional connectivity profiles predict drug responsiveness in patients with temporal lobe epilepsy"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-3321","authenticated-orcid":false,"given":"Kangrun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University Changsha China"},{"name":"Department of Neurosurgery Xiangya Hospital Central South University Changsha 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