Perturbation of resting-state network nodes preferentially propagates to structurally rather than functionally connected regions.

Combining Transcranial Magnetic Stimulation (TMS) with electroencephalography (EEG) offers the opportunity to study signal propagation dynamics at high temporal resolution in the human brain. TMS pulse induces a local effect which propagates across cortical networks engaging distant cortical and subcortical sites. However, the degree of propagation supported by the structural compared to functional connectome remains unclear. Clarifying this issue would help tailor TMS interventions to maximize target engagement. The goal of this study was to establish the contribution of functional and structural connectivity in predicting TMSinduced signal propagation after perturbation of two distinct brain networks. For this purpose, 24 healthy individuals underwent two identical TMS-EEG visits where neuronavigated TMS pulses were delivered to nodes of the default mode network (DMN) and the dorsal attention network (DAN). The functional and structural connectivity derived from each individual stimulation spot were characterized via functional magnetic resonance imaging (fMRI) and Diffusion Weighted Imaging (DWI), and signal propagation across these two metrics was compared. Direct comparison between the signal extracted from brain regions either functionally or structurally connected to the stimulation sites, shows a stronger activation over cortical areas connected via white matter pathways, with a minor contribution of functional projections. This pattern was not observed when analyzing spontaneous resting state EEG activity. Overall, results suggest that structural links can predict network-level response to perturbation more accurately than functional connectivity. Additionally, DWI-based estimation of propagation patterns can be used to estimate off-target engagement of other networks and possibly guide target selection to maximize specificity.