Abstract

Introduction When applying concurrent TMS-EEG, a characteristic waveform – the TMS evoked potential (TEP) – can be measured. The amplitude of an early TEP component (∼20 ms) increased with time awake in healthy subjects ( Huber et al., 2012 ), and long intracortical inhibition (LICI) decreased ( Lang et al., 2011 ), both suggesting an increase in excitability during the day. Excitability was found to be higher in the morning compared to the evening in generalized epilepsy patients ( Badawy et al., 2009 ). For TMS to be of clinical diagnostic use, these diurnal changes should be smaller than the difference in response between epilepsy patients and controls. We studied the influence of the time of day on the overall TEP in healthy controls, using five sessions on one day. Objectives To study the variation of the TEP during the day when stimulating the motor and visual cortex. Subjects and methods TMS-EEG was recorded in 15 healthy subjects using a Magstim Rapid2 stimulator and a 64-channel EEG amplifier (ANT Neuro, Enschede). TMS was targeted at four brain regions: left and right motor cortex (MC), and left and right Brodmann area 19 (B19). At each target, we administered 75 pulses at an intensity of 110% resting motor threshold. Subjects were stimulated during five sessions in one day (8:00 AM, 10:30 AM, 13:00 PM, 15:30 PM and 18:00 PM) while keeping the stimulation intensity constant. Trials were averaged to obtain the TEP. We compared the TEP waveforms between the five sessions with a cluster-based permutation analysis using a dependent t-test and correcting for multiple comparisons (Bonferroni). Results TEPs with components N15, P30, N45, P60, N100 and P180 were present in all subjects after stimulating the MC. The TEP after B19 stimulation consisted of the components N5, P25, N40, P50, N75, P120, N160 and P200. There were no significant differences between the five sessions for both MC and B19 stimulation. Conclusion The TEP is highly reproducible during the day. We found no significant variation of the overall TEP between multiple sessions on one day.

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