Abstract

The large trial-to-trial variability of MEP amplitude in response to TMS may be caused by fluctuations of the endogenous brain state at the time of stimulation. The phase of pericentral m-oscillations is thought to reflect pulsed inhibition at the positive peak, and facilitation (increased excitability) at the negative peak (Jensen and Mazaheri, 2010). Using state-informed EEG-TMS of the left motor hand area, we targeted the pericentral μ-rhythm at four different phases of the endogenous m-oscillations to investigate the state dependency of stimulation. We used real-time EEG analysis to perform state informed TMS, triggering single TMS pulses at a specific phase of the intrinsically expressed pericentral m-rhythm. Endogenous m- activity in the dominant left primary motor hand area was determined based on radial source projection using subject-specific head models and the EEG signal recorded from 63 surface electrodes. Corticospinal excitability was assessed by recording the motor evoked potential (MEP) of the right FDI muscle. Mean MEP amplitudes were compared for stimulation at low (positive peak, 0°) and high (trough, 180°) excitability states, as well as for rising (90°) and falling (270°) phase of the μ-oscillations (60 MEPs per condition). We investigated phase-dependent changes in MEP amplitude, using both biphasic (16 healthy young subjects; 14 females; age range: 20–34 years) and monophasic (15 healthy young subjects; 12 females; age range: 20–39 years) TMS. No pre-selection of subjects was performed to test the applicability of our setup to a general sample. Our state-informed open-loop EEG-TMS setup enabled successful state-informed TMS, hitting the desired phase with a mean absolute error of 48.6° across all trials. Using the MEP amplitude, we tested for differences between high (trough) and low (peak) excitability states, as well as between the rising and falling phase of the μ-oscillation. Neither monophasic TMS nor biphasic TMS yielded significant phase-dependent differences in mean MEP amplitude (two-sided t-tests, p > 0.4 for all comparisons). In a non-preselected sample of healthy young individuals, we did not observe any consistent modulation in mean MEP amplitude depending on the phase of the endogenous m-oscillation at the time of stimulation. Stringent pre-selection of subjects who have a strong and stable pericentral μ-rhythm or a restriction of TMS to periods during which μ-power is even higher, might reveal a significant modulation of MEP amplitude. Acknowledgements: Funded by the Novo Nordisk Foundation Interdisciplinary Synergy Program 2014 (“Biophysically adjusted state-informed cortex stimulation (BASICS); NNF14OC0011413).

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