Visualizing Effective Connectivity in the Human Brain

To enhance mechanistic understanding of effective connectivity in the human brain, we created a tool that links high-temporal resolution transcranial magnetic stimulation electroencephalography (TMS-EEG) with high-spatial resolution diffusion MRI. This tool, Surface to Tractography Real-time EEG Activation Mapping in 4 Dimensions (STREAM-4D), integrates electrophysiologic source estimation models from TMS-evoked potentials (TEPs) with structural connectivity models from diffusion MRI tractography. In a proof-of-principle application, we used STREAM-4D to analyze TMS-EEG and diffusion MRI tractography data in a neurotypical subject across three stimulation sites: premotor, parietal, and occipital cortex. STREAM-4D revealed extensive structural connections associated with the TMS-evoked source models, involving thalamocortical, ipsilateral cortico-cortical, and transcallosal cortico-cortical connections. Activity-weighted structural connectivity differed for the three stimulation sites but shared two extensively connected nodes: the ipsilateral thalamus and putamen. STREAM-4D provides opportunities to elucidate how electrical activity evoked by a TMS pulse is related to underlying white matter architecture.