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 μ-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 μ-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 μ-rhythm represent high- vs. low-excitability states of corticospinal neurons. More importantly, otherwise identical rTMS (200 triple-pulses at 100 Hz burst frequency and ∼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.