Two forms of short-interval intracortical inhibition in human motor cortex

BACKGROUND: Pulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction. OBJECTIVES: To investigate whether SICI evaluated with AP and PA conditioning stimuli (CS(PA) and CS(AP)) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS(PA)). METHODS: Using two superimposed TMS coils, CS(PA) and CS(AP) were applied at interstimulus intervals (ISI) of 1–5 ms before a TS(PA), and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI(CSPA3) and SICI(CSAP3)) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI(CSPA2)), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI(CSPA3) and SICI(CSAP3). RESULTS: CS(AP) produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CS(AP) and CS(PA) were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI(CSPA3) or SICI(CSAP3) with other forms of inhibition led to quite different results: SICI(CSPA3) interacted in complex ways with CBI, SAI and SICI(CSPA2), whereas the effect of SICI(CSAP3) appeared to be quite independent of them. Although SICI(CSPA) and SICI(CSAP) were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI(CSAP) was disinhibited much earlier following the imperative signal than SICI(CSPA). CONCLUSIONS: SICI(CSPA) appears to activate a different inhibitory pathway to that activated by SICI(CSAP). The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.