Accelerated TMS is associated with changes of subgenual cingulate–default mode network coupling in depression: an observational 7 Tesla fMRI study

Abstract Background Accelerated transcranial magnetic stimulation (aTMS) is an effective treatment for depression, but its neurobiological mechanisms of action remain to be elucidated. This study used high-resolution 7-Tesla MRI to investigate changes in resting-state functional connectivity (rs-FC) of the subgenual anterior cingulate cortex (sgACC) following a treatment series of aTMS. We hypothesized a decrease in sgACC rs-FC with key cortical regions of the default mode network (DMN), reflecting a downregulation of a network that is overactive in depression. Methods Twenty-two patients with current depression underwent 7-Tesla MRI scans before and after a two-week aTMS treatment series (24,000 pulses) targeting the left dorsolateral prefrontal cortex. Fourteen healthy participants were also scanned twice as a control group. Longitudinal changes in sgACC seed-based rs-FC were compared between groups. Furthermore, group differences were assessed at baseline and at follow-up. Exploratory correlations between longitudinal changes in sgACC rs-FC, depression severity, mindfulness, and affect were also evaluated. Results There was a reduction in rs-FC between the sgACC and bilateral precunei, and between sgACC and left frontal pole in patients receiving aTMS. At baseline, patients had increased rs‑FC between the sgACC and a cluster including the left precuneus and a cluster in the right superior frontal gyrus. Exploratory correlations suggest an association between sgACC-precunei rs-FC changes and mindfulness ( p = 0.008, uncorrected for multiple comparisons), while no associations were found with depression severity or affect. Conclusions Treatment with aTMS is associated with a reduction in rs‑FC between the sgACC and the DMN. Exploratory correlations with mindfulness warrant replication in larger, independent samples.