Can Oscillatory Alpha-Gamma Phase-Amplitude Coupling be Used to Understand and Enhance TMS Effects?

Recent applications of simultaneous scalp electroencephalography (EEG) and transcranial magnetic stimulation (TMS) suggest that adapting stimulation to underlying brain states may enhance neuroplastic effects of TMS. It is often assumed that longer-lasting effects of TMS on brain function may be mediated by phasic interactions between TMS pulses and endogenous cortical oscillatory dynamics. The mechanisms by which TMS exerts its neuromodulatory effects, however, remain unknown. Here, we discuss evidence concerning the functional effects on synaptic plasticity of oscillatory cross-frequency coupling in cortical networks as a potential framework for understanding the neuromodulatory effects of TMS. We first discuss evidence for interactions between endogenous oscillatory brain dynamics and externally induced electromagnetic field activity. Alpha band (8-12 Hz) activities are of special interest here because of the wide application and therapeutic effectiveness of rhythmic TMS (rTMS) using a stimulus repetition frequency at or near 10 Hz. We discuss the large body of literature on alpha oscillations suggesting that alpha oscillatory cycles produce periodic inhibition or excitation of neuronal processing through phase-amplitude coupling (PAC) of low-frequency oscillations with high-frequency broadband (or gamma) bursting. Such alpha-gamma coupling may reflect excitability of neuronal ensembles underlying neuroplasticity effects of TMS. We propose that TMS delivery with simultaneous EEG recording and near real-time estimation of source-resolved alpha-gamma PAC might be used to select the precise timing of TMS pulse deliveries so as to enhance the neuroplastic effects of TMS therapies.