• Stephan F Taylor, S Shaun Ho, Tessa Abagis, Mike Angstadt, Daniel F Maixner, Robert C Welsh, and Luis Hernandez-Garcia.
• Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. Electronic address: sftaylor@umich.edu.
• J Affect Disord. 2018 May 1; 232: 143-151.

BackgroundThe subgenual anterior cingulate cortex (sgACC) has been implicated in major depressive disorder (MDD), and this study evaluated sgACC connectivity before and after repetitive transcranial magnetic stimulation (rTMS) treatment.MethodsThirty-two MDD patients entered a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex (dlFPC). Subjects underwent resting state functional magnetic resonance imaging before and after 20 sessions of high frequency rTMS. Seed voxels identified the affective network (AN; sgACC, amygdala), default mode network (DMN; posterior cingulate cortex [PCC]), and fronto-parietal network (FPN; dlPFC stimulation site).ResultsThere was no significant effect of active rTMS over sham on the primary outcome measure (Montgomery-Asberg Depression Scale rating), with both groups improving over time, and no specific effect of rTMS (sham vs active) on connectivity. However, among patients who showed significant improvement, sgACC connectivity decreased for sham (to AN, trend to DMN) and active rTMS responders (to AN, DMN, FPN), but not in non-responders, who tended to maintain connectivity. Including subjects who started with sham but then received open-label active treatment, baseline connectivity from the PCC to the anterior insula was greater in non-responders compared to responders (n = 27, excluding 5 sham responders).LimitationsThe sample size was small; the stimulation target was non-standard, and the lack of a significant clinical effect of rTMS limits conclusions about negative findings.ConclusionssgACC connectivity reduces along with depressive symptoms, not specific to rTMS therapy. Altered connectivity of DMN with anterior insula may reflect a type of patient less likely to respond to an intervention.Copyright © 2018 Elsevier B.V. All rights reserved.

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