iTBS induces a suppression-rebound pattern in human cortical excitability

Intermittent theta burst stimulation (iTBS) is a widely used form of brain stimulation, developed on the premise that it promotes long-term potentiation (LTP) and neural excitation. However, this is not validated in higher-order neocortex, and evidence suggests its excitatory properties may have been overstated. To address this, we recruited 20 neurosurgical patients to undergo sessions of intracranial iTBS to varied targets. We probed changes in cortical reactivity with single pulse electrical stimulation, finding that iTBS resulted in approximately 1 minute of decreased cortical reactivity in the theta and high-frequency ranges in regions strongly connected to the stimulation site. However, we observed a subsequent rise in reactivity leading up to the next iTBS session with parallel changes in resting state excitation/inhibition balance. Finally, we generalized these findings to 3 neurosurgical patients who underwent iTBS delivered by transcranial magnetic stimulation, demonstrating a similar suppression-rebound pattern. Our results suggest iTBS promotes a dynamic process of cortical suppression followed by rebound increases in excitability.