Pregenual or subgenual anterior cingulate cortex as potential effective region for brain stimulation of depression

Background The dorsolateral prefrontal cortex (DLPFC) is the standard stimulation target for the repetitive transcranial magnetic stimulation (rTMS) treatment of major depression disorder (MDD). A retrospective study by Fox and colleagues found that a more negative resting-state functional magnetic resonance imaging (RS-fMRI) functional connectivity (FC) between left DLPFC and the subgenual anterior cingulate cortex (sgACC) in a large group of healthy participants is associated with a better curative effects of rTMS in MDD, suggesting that the sgACC may be an effective region. However, a recent meta-analysis on RS-fMRI studies found that the pregenual ACC (pgACC), rather than the sgACC, of MDD patients showed increased local activity. Methods We used the stimulation coordinates in the left DLPFC analyzed by Fox et al. to perform RS-fMRI FC between the stimulation targets obtained from previous rTMS MDD studies and the potential effective regions (sgACC and pgACC, respectively) on the RS-fMRI data from 88 heathy participants. Results (a) Both the pgACC and the sgACC were negatively connected to the left DLPFC; (b) both FCs of sgACC-DLPFC and pgACC-DLPFC were more negative in responders than in nonresponders; and (c) the associations between DLPFC-sgACC functional connectivity and clinical efficacy were clustered around the midline sgACC. Conclusions Both the pgACC and the sgACC may be potential effective regions for rTMS on the left DLPFC for treatment of MDD. However, individualized ACC-DLPFC FC-based rTMS on depression should be performed in the future to test the pgACC or the sgACC as effective regions.