Short-interval intracortical inhibition is related to high-frequency cortico-cortical functional connectivity in the human brain

Short-interval intracortical inhibition (SICI), a paired-pulse transcranial magnetic stimulation (pp-TMS) paradigm, provides an in vivo marker of GABA-A-mediated inhibitory tone in the human cortex. SICI has been extensively characterized at the local level, but its relationship with brain network dynamics remains unclear. Here, we investigated whether interindividual variability in SICI correlates with resting-state functional connectivity (FC) derived from high-density EEG (HD-EEG). Eighteen healthy volunteers underwent HD-EEG followed by pp-TMS based assessment of SICI and intracortical facilitation. FC was computed in source space across canonical frequency bands using the weighted phase lag index, and its association with conditioned motor-evoked potentials (MEPs) was tested using network-based statistics. Stronger FC in β and high-γ bands was positively associated with reduced inhibition (ie larger conditioned MEPs) at ISI 2 ms. These networks prominently involved sensorimotor, prefrontal, and temporo-parietal regions (β) as well as parieto-occipital, sensorimotor, and temporal regions (γ). Our findings provide the first electrophysiological evidence that local inhibitory tone is mirrored by large-scale frequency-specific networks in the healthy brain. This multimodal approach advances the understanding of how GABA-A-mediated inhibition shapes cortical network organization and may inform future studies on disease-related alterations of inhibitory dynamics.