Conventional or threshold-hunting TMS? A tale of two SICIs

Background: In human primary motor cortex (M1), the paired-pulse transcranial magnetic stimulation (TMS) paradigm of short-interval intracortical inhibition (SICI) can be expressed conventionally as a percent change in the relative amplitude of a conditioned motor evoked potential to non-conditioned; or adaptive threshold-hunting a target motor evoked potential amplitude in the absence or presence of a conditioning stimulus, and noting the relative change in stimulation intensity. The suitability of each approach may depend on the induced current direction, which probe separate M1 interneuronal populations. Objective: To examine the influence of conditioning stimulus intensity, interstimulus interval (ISI) and current direction for adaptive threshold-hunting and conventional SICI using equivalent TMS intensities. Methods: In 16 participants (21–32 years), SICI was examined using adaptive threshold-hunting and conventional paired-pulse TMS with posterior-anterior and anterior-posterior stimulation, ISIs of 2 and 3 ms, and a range of conditioning intensities. Results: Inhibition with adaptive threshold-hunting was greater for anterior-posterior stimulation with an ISI of 3 ms (23.6 ± 9.0%) compared with 2 ms (7.5 ± 7.8%, P < 0.001) and posterior-anterior stimulation at both ISIs (2 ms 8.6 ± 8.7%, 3 ms 5.9 ± 4.8%; P < 0.001). There was an association between inhibition obtained with conventional and adaptive threshold-hunting for posterior-anterior but not anterior-posterior stimulation (2 ms only, r = 0.68, P = 0.03). Conclusions: More inhibition was evident with anterior-posterior than posterior-anterior current for both adaptive threshold-hunting and conventional paired-pulse TMS. Assessment of SICI with anterior-posterior stimulation was not directly comparable between the two approaches. However, the amount of inhibition was dependent on conditioning stimulus intensity and ISI for both SICI techniques.