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

Abstract

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.