The Effects of Waveform and Current Direction on the Efficacy and Test-Retest Reliability of Transcranial Magnetic Stimulation.

The pulse waveform and current direction of transcranial magnetic stimulation (TMS) influence its interactions with the neural substrate; however, their role in the efficacy and reliability of single- and paired-pulse TMS measures is not fully understood. We investigated how pulse waveform and current direction affect the efficacy and test-retest reliability of navigated, single- and paired-pulse TMS measures. 23 healthy adults (aged 18-35 years) completed two identical TMS sessions, assessing resting motor threshold (RMT), motor-evoked potentials (MEPs), cortical silent period (cSP), short- and long-interval intra-cortical inhibition (SICI and LICI), and intracortical facilitation (ICF) using either monophasic posterior-anterior (mono; n = 9), monophasic anterior-posterior (mono; n = 7), or biphasic (bi; n = 7) pulses. Averages of each TMS measure were compared across the three groups and intraclass correlation coefficients were calculated to assess test-retest reliability. RMT was the lowest and cSP was the longest with bi pulses, whereas MEP latency was the shortest with mono pulses. SICI and LICI had the largest effect with mono pulses, whereas only mono and bi pulses resulted in significant ICF. MEP amplitude was more reliable with either mono or mono than with bi pulses. LICI was the most reliable with mono pulses, whereas ICF was the most reliable with bi pulses. Waveform/current direction influenced RMT, MEP latency, cSP, SICI, LICI, and ICF, as well as the reliability of MEP amplitude, LICI, and ICF. These results show the importance of considering TMS pulse parameters for optimizing the efficacy and reliability of TMS neurophysiologic measures.