Resting state fMRI based target selection for personalized rTMS: stimulation over the left DLPFC temporarily alters the default mode network in healthy subjects

Abstract

High frequency repetitive TMS (HF-rTMS) to the left dorsolateral prefrontal cortex (DLPFC) is an approved option for the treatment of depression, but there is also much variability in the resulting antidepressant response. This variability is believed to arise from various factors, an important one of which being the method by which rTMS is targeted to the optimal stimulation site in the left DLPFC. To more accurately target HF-rTMS at left DLPFC, we present a new method for target selection based on individual RS-fMRI data. We show in 23 healthy subjects that the new proposed method of target selection is reproducible and yields left DLPFC targets whose functional connectivity correlates more negatively with subgenual anterior cingulate cortex (sgACC) than targets based on standard MNI coordinates. Since previous work has highlighted higher negative connectivity with the sgACC as an important feature of targets for higher antidepressant effect of HF-rTMS, the targets selected by the new method can be expected to lead to a higher therapeutic response. Additionally, the mechanism of action of an entire single session of HF-rTMS (3000 pulses) in healthy subjects has not been reported. We show significant decreases in functional connectivity of the default mode network in sgACC and ventral striatum (vStr) regions, peaking at 27-32 minutes after stimulation. Also, we report a negative correlation between the magnitude of this decrease in the right sgACC and the harm avoidance domain measure from the Temperament and Character Inventory (TCI). This finding points towards the possibility of using the harm avoidance measure as a predictor of HF-rTMS response. In addition, the decreased functional connectivity of the default mode network in right nucleus accumbens (NAcc) correlates with a short-term decrease in self-rated negative emotions from the Positive and Negative Affect Schedule (PANAS) i.e. the lower the functional connectivity of right NAcc with the default mode network, the lower the reported perception of negative mood by the subjects. This suggests a mechanism by which changes induced by rTMS influence the perception of negative mood in recipients.