Short-interval intracortical inhibition and facilitation targeting the tibialis anterior muscle

Background Paired-pulse transcranial magnetic stimulation (TMS) combines two single pulses, a conditioning pulse (S1) and a testing pulse (S2), with a given inter-stimulus interval (ISI). In upper limb muscles, the interaction between short interval intracortical inhibition (SICI) and facilitation (SICF) is thoroughly examined (Ilić et al., JPhysiol., 2002), while relatively little is known for lower limb muscles. SICI and SICF are thought to be caused by interaction of I3 waves (Hanajima et al., JPhysiol., 1998; Hanajima et al., JPhysiol., 2002) and while these can be elicited in upper limb muscles, TMS activation of lower limbs tend to predominantly activate I1 waves given the histological differences (Terao et al., Brain Research, 2000). In the present study, we investigated the effects of stimulation intensities of S1 and S2 on motor cortex (M1) excitability targeting the tibialis anterior (TA) muscle. Methods Pairs of transcranial magnetic stimuli with an ISI of 1.5 ms were applied over the M1 representation of TA using a figure-of-eight coil, resulting in an induced electric field travelling in a medial to lateral direction. Ten healthy participants were examined for this study (mean age: 23.4±2.7 years). Motor evoked potentials (MEPs) from the resting TA muscle were measured using electromyography (EMG). The intensities of S1 and S2 in all trials were varied randomly in steps of 10% resting motor threshold (RMT) between 60 and 140% RMT (i.e., nine conditions). The paired-pulse conditions consisted of all possible combinations of S1 and S2 intensities. In addition, nine single-pulse conditions were tested. Paired t-tests (two-way) were performed for statistical analysis and all multiple comparisons were corrected using Holm-Bonferroni’s method. Results When expressing the interaction between S1 and S2 as MEPS1+S2/(MEPS1+MEPS2), the activation of inhibitory and excitatory circuits was found to be dependent on the stimulating conditions as registered in upper limbs. When S1 < RMT and S2 > RMT, an inhibitory interaction of S1 and S2 occurred. For the typical setting for S1 and S2 used in upper limb muscles, S1=80%RMT and S2=120%RMT, SICI was observed in eight out of ten participants. The optimal stimulation condition inducing SICI in all ten participants was S1=70%RMT and S2=130%RMT (p<0.0006), which suppressed the MEPs to 49%. When S1 was close to or equal to RMT and S2 was slightly below RMT, an excitatory interaction (i.e., SICF) of S1 and S2 occurred. The typical settings in upper limb muscles, S1=130%RMT and S2=90%RMT and S1=S2=100%RMT, resulted in SICF in eight out of ten and seven out of ten participants respectively. The optimal stimulation condition inducing SICF in all ten participants was S1=90%RMT and S2=90%RMT, which elicited a MEP of 448%. However, this was not significant (p=0.005) given stringent statistical tests. Conclusion The present study demonstrated that it is possible to record excitatory and inhibitory interaction when stimulating the TA representation in M1 with paired-pulse TMS. The interaction appears to be dependent on the intensities of the two pulses, as has been reported for upper limb muscles. Significance Statement This study provides evidence that SICI and SICF targeting the lower limb muscle TA is dependent on intensities of S1 and S2 when using paired-pulse TMS. Data reveal the optimal combination of stimulation intensities that result in SICI or SICF for future studies and clinical trials.