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

Abstract 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 PA ; n  = 9), monophasic anterior–posterior (mono AP ; n  = 7), or biphasic (bi AP-PA ; 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 AP-PA pulses, whereas MEP latency was the shortest with mono PA pulses. SICI and LICI had the largest effect with mono PA pulses, whereas only mono AP and bi AP-PA pulses resulted in significant ICF. MEP amplitude was more reliable with either mono PA or mono AP than with bi AP-PA pulses. LICI was the most reliable with mono AP pulses, whereas ICF was the most reliable with bi AP-PA 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.