Systematic cross-species comparison of prefrontal cortex functional networks targeted via Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation method that safely modulates neural activity in vivo. Its precision in targeting specific brain networks makes TMS invaluable in diverse clinical applications. For example, TMS is used to treat depression by targeting prefrontal brain networks and their connection to other brain regions. However, despite its widespread use, the underlying neural mechanisms of TMS are not completely understood. Non-human primates (NHPs) offer an ideal model to study TMS mechanisms through invasive electrophysiological recordings. As such, bridging the gap between NHP experiments and human applications is imperative to ensure translational relevance. Here, we systematically compare the TMS-targeted functional networks in the prefrontal cortex in humans and NHPs. To conduct this comparison, we combine TMS electric field modeling in humans and macaques with resting-state functional magnetic resonance imaging (fMRI) data to compare the functional networks targeted via TMS across species. We identified distinct stimulation zones in macaque and human models, each exhibiting variations in the impacted networks (macaque: Frontoparietal Network, Somatomotor Network; human: Frontoparietal Network, Default Network). We identified differences in brain gyrification and functional organization across species as the underlying cause of found network differences. The TMS-network profiles we identified will allow researchers to establish consistency in network activation across species, aiding in the translational efforts to develop improved TMS functional network targeting approaches.