• Conor Liston, Ashley C Chen, Benjamin D Zebley, Andrew T Drysdale, Rebecca Gordon, Bruce Leuchter, Henning U Voss, B J Casey, Amit Etkin, and Marc J Dubin.
• Department of Psychiatry and Behavioral Sciences (CL, ACC, AE), Stanford University School of Medicine, Palo Alto, California; Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College. Electronic address: col2004@med.cornell.edu.
• Biol. Psychiatry. 2014 Oct 1;76(7):517-26.

BackgroundRepetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks-the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)-are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response.MethodsWe used resting state functional magnetic resonance imaging to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a 5-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared with a cohort of 35 healthy control subjects.ResultsBefore treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. Transcranial magnetic stimulation normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. Transcranial magnetic stimulation also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement.ConclusionsTranscranial magnetic stimulation selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response.Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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