Dorsolateral prefrontal cortex to subgenual cingulate anticorrelation predicts subgenual cingulate response from prefrontal stimulation.

OBJECTIVE: Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) may achieve its antidepressant effect via transsynaptic activation of the subgenual cingulate (SGC). SGC activation by DLPFC TMS can be quantified by concurrent EEG (TMS-EEG) via source localization, while the connection between the DLPFC and SGC can be quantified by resting state functional connectivity (RSFC). Here, the relationship between SGC source activation and DLPFC-SGC anticorrelation is characterized in depression patients. METHODS: TMS-EEG and fMRI were collected from 42 depression patients before a course of accelerated individualized intermittent theta-burst stimulation treatment. SGC activation by single pulse TMS of the individual target was quantified by the cortical evoked activity (CEA, 20-500 ms) and the negative peak near 100 ms (N100) of the region's evoked potential. Correlations between the TMS-EEG measures and DLPFC-SGC RSFC were calculated. RESULTS: Stronger DLPFC-SGC anticorrelation was associated with smaller SGC N100 (Rho = -0.36, Pval = 0.03). There was no correlation between the baseline depression symptoms assessed with MADRS and neither the DLPFC-SGC anticorrelation nor the TEP-based SGC measures. CONCLUSIONS: Higher anticorrelation between the DLPFC and SGC enables TMS pulses delivered to the DLPFC to better modulate activity at the SGC. SIGNIFICANCE: This study adds to current understanding of the DLPFC to SGC pathway. Multimodal studies with TMS-EEG and fMRI measures of network pathways may provide missing links in understanding of depression pathophysiology.