Although the hippocampus is not considered a key structure in semantic memory, patients with medial-temporal lobe epilepsy (mTLE) have deficits in semantic access on some word retrieval tasks. We hypothesized that these deficits reflect the negative impact of focal epilepsy on remote cerebral structures. Thus, we expected that the networks that support word retrieval tasks would be altered in left mTLE patients. We measured brain activity with fMRI while participants (13 controls, 13 left mTLE, and 13 right mTLE) performed a verb generation task. We examined functional connectivity during this task in relation to language performance on an off-line clinical test of lexical access (Boston Naming Test, BNT). Using task–seed–behavior partial least squares, we identified a canonical language network that was more active during verb generation than the baseline condition, but this network did not correlate with variability in BNT performance in either controls or patients. Instead, additional networks were identified for each group, with more anterior temporal and prefrontal regions recruited for controls and more posterior temporal regions for both left and right mTLE patients. Our findings go beyond the literature emphasizing differences in laterality of language processes in mTLE patients and, critically, highlight how network changes can be used to account for performance variation among patients on clinically relevant measures. This strategy of correlating network changes and off-line behavior may provide a powerful tool for predicting a postoperative decline in language performance.

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