Threshold tracking primary motor cortex inhibition: the influence of current direction

Paired-pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior-posterior (AP) stimulation preferentially activates late indirect- (I-) waves that are most susceptible to paired-pulse TMS. Threshold tracking TMS can assess intracortical inhibition; however, previous studies have only used a current direction that preferentially recruits early I-waves [posterior-anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I-waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21-50 years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I-wave recruitment calculated as the onset latency difference between PA-LM and AP-LM. Short- and long-interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100-260 ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I-wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP-induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA.