Resting fMRI-guided TMS evokes subgenual anterior cingulate response in depression

Abstract

Depression alleviation following treatment with repetitive transcranial magnetic stimulation (rTMS) tends to be more effective when TMS is targeted to cortical areas with high resting state functional connectivity (rsFC) with the subgenual anterior cingulate cortex (sgACC). However, it has not yet been confirmed that rsFC-guided TMS coil placement leads to TMS modulation of the sgACC. For each participant (N=115, 34 depressed patients), a peak rsFC cortical hotspot for the sgACC and control targets were prospectively identified. Single pulses of TMS interleaved with fMRI readouts were then administered to these targets and established significant downstream fMRI BOLD responses in the sgACC. We then marked an association between TMS-evoked BOLD responses in the sgACC and rsFC between the stimulation site and sgACC. This effect was qualified by a difference between healthy and patient participants: only in depressed patients, positively connected sites of stimulation led to the strongest evoked responses in the sgACC. Our results highlight rsFC-based targeting as a viable strategy to causally modulate sgACC subcortical targets and further suggest that cortical sites with high positive rsFC to the sgACC might represent an alternative target for the treatment of depression.

Clinical Response to fMRI-guided Compared to Non-Image Guided rTMS in Depression and PTSD: A Randomized Trial

“…We have previously demonstrated the promise of our novel fMRI-guided rTMS target over anticorrelated subgenual anterior cingulate targets to engage the sgACC in patients, as measured by online interleaved TMS/fMRI. 5 On the clinical side, our symptom reduction for the fMRI-guided protocol was 67% for depression, which falls in the range of the latest Stanford (SNT) protocol (62-86% reduction 3,4 ), outstrips the recent fMRI-guided BRIGhTMIND British protocol (37% reduction 2 ), and the Canadian THREE-D structural MRI based target (43% reduction 1 ). This improvement is also substantially better than their F3 scalp target (35% reduction) as well as the original 5cm target from Penn (18-23% reduction 16 ).…”

“…The fMRI-guided target in the present study was also the sgACC, but it was defined using positive functional connectivity (FC) connections rather than negatively correlated connections explored in most prior studies, which we chose in light of recent interleaved TMS/fMRI evidence for superior sgACC engagement in patients using this target. 5 The sgACC has been shown to be consistently hyperactive in major depression disorder (MDD) 6 as well as in post-traumatic stress disorder (PTSD), 7 likely due to diagnostic and symptom overlaps between the two conditions. 8,9 Clinical improvements following rTMS treatment are associated with sgACC connectivity changes on both depression and PTSD symptom scales.…”