Electroconvulsive therapy improves functional connectivity of the frontoparietal network and language network in patients with treatment-resistant depression.

Previous studies have reported abnormal functional connectivity (FC) in patients with treatment-resistant depression (TRD); however, the FC patterns of the frontoparietal network (FPN) and language network (LN) remained unclear. Electroconvulsive therapy (ECT) is regarded as a one of the most effective treatments for patients with TRD. Despite its high efficacy, the underlying mechanisms of ECT remain largely unknown. Seed-based FC analysis was performed using imaging data from 72 patients with TRD (with 52 finishing the follow-up) and 63 healthy controls (HCs) to detect FC patterns of the FPN and LN before and after ECT. Neuroimaging-transcription association analyses were also performed. At baseline, patients with TRD presented decreased FCs within the FPN (inferior frontal gyrus, middle frontal gyrus, and superior frontal gyrus) as well as between the FPN/LN and the somatomotor network (SMN, precentral gyrus, postcentral gyrus, and supplementary motor area) and the default mode network (DMN, supramarginal gyrus and hippocampus). Following ECT, the clinical symptoms of patients showed a significant reduction. There were increased FCs within the FPN (inferior frontal gyrus and superior frontal gyrus), as well as between the FPN/LN and DMN (anterior cingulate cortex, precuneus, and angular gyrus). Genes associated with baseline case-control FC alterations were primarily enriched in ion channel activity and synaptic function. TRD might involve reduced functional integration between higher-order cognitive, sensory, and self-referential systems. The antidepressant effects of ECT may involve modulating FCs within the higher-order cognitive regions and between cognitive and self-referential systems to support emotion and cognitive regulation.