RESUMO
Understanding how spontaneous brain activity influences the response to neurostimulation is crucial for the development of neurotherapeutics and brain-computer interfaces. Localized brain activity is suggested to influence the response to neurostimulation, but whether fast-fluctuating (i.e., tens of milliseconds) large-scale brain dynamics also have any such influence is unknown. By stimulating the prefrontal cortex using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG), we examined how dynamic global brain state patterns, as defined by microstates, influence the magnitude of the evoked brain response. TMS applied during what resembled the canonical microstate C was found to induce a greater evoked response for up to 80 milliseconds compared to other microstates. This effect was found in a repeated experimental session, was absent during sham stimulation, and was replicated in an independent dataset. Ultimately, ongoing and fast-fluctuating global brain states, as probed by microstates, may be associated with intrinsic fluctuations in connectivity and excitation-inhibition balance and influence the neurostimulation outcome. We suggest that the fast-fluctuating global brain states be considered when developing any related paradigms.Significance Statement Previous findings suggested local spontaneous neural oscillations can influence neurophysiological response to stimuli. However, beyond the local oscillatory activity, the brain state is rapidly fluctuating on a millisecond time resolution on a global spatial scale. We investigated whether these rapid global fluctuations influenced the evoked response to brain stimulation. We used combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to stimulate the prefrontal cortex while recording global brain states via EEG microstates. The evoked neurophysiological response was significantly larger when stimulation was applied after the occurrence of a specific global brain state (i.e., microstate C) linked to mind-wandering. The finding was selective to active stimulation, replicated for the same individuals in a repeated session, and replicated in an entirely independent dataset.