Abstract

Transcranial magnetic stimulation (TMS) is an FDA-approved neuromodulation treatment for major depressive disorder (MDD), thought to work by altering dysfunctional brain connectivity pathways, or by indirectly modulating the activity of subcortical brain regions. Clinical response to TMS remains highly variable, highlighting the need for baseline predictors of response and for understanding brain changes associated with response. This systematic review examined brain connectivity features, and changes in connectivity features, associated with clinical improvement following TMS in MDD. Forty-one studies met inclusion criteria, including 1097 people with MDD. Most studies delivered one of two types of TMS to left dorsolateral prefrontal cortex and measured connectivity using resting-state functional MRI. The subgenual anterior cingulate cortex was the most well-studied brain region, particularly its connectivity with the TMS target or with the "executive control network" of brain regions. There was marked heterogeneity in findings. There is a need for greater understanding of how cortical TMS modulates connectivity with, and the activity of, subcortical regions, and how these effects change within and across treatment sessions.