Real-time EEG-defined excitability states determine efficacy of TMS-induced plasticity in human motor cortex

Background: Rapidly changing excitability states in an oscillating neuronal network can explain response variability to external stimulation, but if repetitive stimulation of always the same high-or low-excitability state results in long-term plasticity of opposite direction has never been explored in vivo. Objective/hypothesis: Different phases of the endogenous sensorimotor m-rhythm represent different states of corticospinal excitability, and repetitive transcranial magnetic stimulation (rTMS) of always the same high-vs. low-excitability state results in long-term plasticity of different direction. Methods: State-dependent electroencephalography-triggered transcranial magnetic stimulation (EEG-TMS) was applied to target the EEG negative vs. positive peak of the sensorimotor mu-rhythm in healthy subjects using a millisecond resolution real-time digital signal processing system. Corticospinal excitability was indexed by motor evoked potential amplitude in a hand muscle. Results: EEG negative vs. positive peak of the endogenous sensorimotor m-rhythm represent high-vs. low-excitability states of corticospinal neurons. More importantly, otherwise identical rTMS (200 triple-pulses at 100 Hz burst frequency and similar to 1 Hz repetition rate), triggered consistently at this high-excitability vs. low-excitability state, leads to long-term potentiation (LTP)-like vs. no change in corticospinal excitability. Conclusions: Findings raise the intriguing possibility that real-time information of instantaneous brain state can be utilized to control efficacy of plasticity induction in humans. (C) 2017 Elsevier Inc. All rights reserved.