Changes in brain connectivity during a sham-controlled, transcranial magnetic stimulation trial for depression

• Published in: Journal of affective disorders Vol. 232; pp. 143 - 151
• Main Authors: Taylor, Stephan F., Ho, S. Shaun, Abagis, Tessa, Angstadt, Mike, Maixner, Daniel F., Welsh, Robert C., Hernandez-Garcia, Luis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: Adult; Anterior insula; Brain - diagnostic imaging; Brain - physiopathology; Default mode network; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - physiopathology; Depressive Disorder, Major - therapy; Dorsolateral prefrontal cortex; Female; Functional magnetic resonance imaging; Gyrus Cinguli - diagnostic imaging; Gyrus Cinguli - physiopathology; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net - diagnostic imaging; Nerve Net - physiopathology; Placebo; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - physiopathology; Subgenual cingulate gyrus; Transcranial Magnetic Stimulation - methods; Dorsolateral prefrontal cortex; Functional magnetic resonance imaging; Default mode network; Anterior insula; Subgenual cingulate gyrus; Placebo
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2018.02.019

The 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. Thirty-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). There 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). The 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. sgACC 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. •Subgenual connectivity decreased with response to sham and active treatment.•Connectivity decreased within affective network and with default mode network.•No differential effect of active versus sham TMS on connectivity.•sgACC connectivity change may be a final common pathway in depression treatment.•Baseline default mode connectivity predicted symptom change.