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TMS-Evoked Responses Are Driven by Recurrent Large-Scale Network Dynamics

A major question in systems and cognitive neuroscience is to what extent neurostimulation responses are driven by recurrent activity. This question finds sharp relief in the case of TMS-EEG evoked potentials (TEPs). TEPs are spatiotemporal waveform patterns with characteristic inflections at ∼50ms, ∼100ms, and ∼150-200ms following a single TMS pulse that disperse from, and later reconverge to, the primary stimulated regions. What parts of the TEP are due to recurrent activity? And what light might this shed on more general principles of brain organization? We studied this using source-localized TMS-EEG analyses and whole-brain connectome-based computational modelling. Results indicated that recurrent network feedback begins to drive TEP responses from ∼100ms post-stimulation, with earlier TEP components being attributable to local reverberatory activity within the stimulated region. Subject-specific estimation of neurophysiological parameters additionally indicated an important role for inhibitory GABAergic neural populations in scaling cortical excitability levels, as reflected in TEP waveform characteristics.