Accelerated TMS normalizes subgenual cingulate–default mode network coupling in depression: An observational 7 Tesla fMRI study

Background Repetitive transcranial magnetic resonance imaging is an effective treatment for depression. Accelerated TMS-protocols (aTMS) are applied several times per day and hold promise to rapidly decrease depressive symptoms. This study used high-resolution 7-Tesla MRI to anatomically precisely investigate aTMS-induced alterations of resting state functional connectivity (rs-FC) of the subgenual anterior cingulate cortex (sgACC). We hypothesized that aTMS reduces hyperactivation of the sgACC by decreasing rs-FC with key cortical regions. Furthermore, we explore associations between sgACC related rs-FC alterations, depression severity and mindfulness, which is often impaired in depression. Methods Twenty-four patients with current depression underwent 7-Tesla MRI-scans before and after a two-week aTMS treatment series (target: left dorsolateral prefrontal cortex, total number of pulses: 24,000). Fifteen healthy controls were also scanned twice for comparison, without receiving aTMS. Group × time interactions of changes in sgACC seed-based rs-FC were calculated. In addition, we examined baseline group differences of sgACC rs-FC. Correlations between longitudinal changes in sgACC rs-FC, depression severity, and mindfulness, were calculated. Results aTMS reduced rs-FC between the sgACC and the precuneus (core part of the default mode network; DMN), normalizing elevated baseline rs‑FC in depressed patients. No significant association was observed with changes in overall depression severity. However, decreases in sgACC–posterior DMN connectivity were significantly associated with improvements in mindfulness. Conclusions Treatment response in depression is associated with a normalization of rs‑FC alterations between the sgACC and the DMN. Observed changes might reflect processes related to improvements in mindfulness.