Brain stimulation is used clinically to treat a variety of neurological and psychiatric conditions. The mechanisms of the clinical effects of these brain-based therapies are presumably dependent on their effects on brain networks. It has been hypothesized that using individualized brain network maps is an optimal strategy for defining network boundaries and topologies. Traditional non-invasive imaging can determine correlations between structural or functional time series. However, they cannot easily establish hierarchies in communication flow as done in non-human animals using invasive methods. In the present study, we interleaved functional MRI recordings with non-invasive transcranial magnetic stimulation in the attempt to map causal communication between the prefrontal cortex and two subcortical structures thought to contribute to affective dysregulation: the subgenual anterior cingulate cortex (sgACC) and the amygdala. In both cases, we found evidence that these brain areas were engaged when TMS was applied to prefrontal sites determined from each participant's previous fMRI scan. Specifically, after transforming individual participant images to within-scan quantiles of evoked TMS response, we modeled the average quantile response within a given region across stimulation sites and individuals to demonstrate that the targets were differentially influenced by TMS. Furthermore, we found that the sgACC distributed brain network, estimated in a separate cohort, was engaged in response to sgACC focused TMS and was partially separable from the proximal default mode network response. The amygdala, but not its distributed network, responded to TMS. Our findings indicate that individual targeting and brain response measurements usefully capture causal circuit mapping to the sgACC and amygdala in humans, setting the stage for approaches to non-invasively modulate subcortical nodes of distributed brain networks in clinical interventions and mechanistic human neuroscience studies.

Individualized non-invasive brain stimulation engages the subgenual anterior cingulate and amygdala