IS 7. News about short interval intracortical inhibition (SICI)

Abstract

Conditioned transcranial magnetic stimulation (TMS) techniques have been proposed to reflex many intracortical inhibition or facilitation mechanisms of the primary motor cotex (M1). Conditioning stimuli (CS) at intensity below threshold over M1 suppressed MEP to test stimuli given through the same coil at interstimulus intervals (ISIs) of 1–5 ms (Kujirai methods). The inhibition is called as short interval intracortical inhibition (SICI) and has been considered as one of basic tool to evaluate cortical excitability changes. 1. Physiological features of SICI: SICI was reported to be a cortical inhibition, because neither H-waves nor MEPs to transcranial electrical stimulation were affected. Only later I-waves, probably induced though several synapses in M1, are suppressed by CS, but I1-waves are not. Pharmacological studies showed that GABAA mediated mechanisms could contribute to SICI. The GABAergic inhibition, however, lasts longer than 5 ms even though SICI lasts 5 ms. The GABAergic inhibition may not explain SICI at all 1–5 ms intervals. Inhibition at 1 ms interval mainly reflects the refractory period. Those at 2–5 ms intervals may be produced mainly by GABAergic inhibition. Another point to mind is the mask of inhibition by some facilitation mechanisms. The intracortical facilitation overlaps GABAergic inhibition at later intervals, which must mask the longer part of inhibition. Even at short intervals, short intervals intracortical facilitation (SICF) overlaps it when the CS intensity is too high. When the amount of SICI is reduced in the experiment, we should not simply conclude that the GABAergic inhibition is reduced and consider contamination of these cofounding mechanisms. We should consider the possibility that the MEP could are composed mainly by D-waves or I1-waves and the possibility that the some enhanced intracortical facilitation mask normal inhibition. I will present some example. SICI test showed inhibition reduction in Parkinson’s disease (PD) with usual Kujirai methods. However, when CS was set at 80% RMT, the amount of SICI at an ISI of 3 ms in PD was similar to that in healthy volunteers. Moreover, when using TMS pulse with AP directed currents, normal inhibition was induced and it continued longer than 5 ms probably because AP directed currents produces mainly I3-waves. These findings suggested that M1 GABAergic inhibition is not affected in PD, but some confounding factors may affect the results of SICI experiment. 2. SICI and cortical plasticity: Repetitive TMS (rTMS) noninvasively induces long lasting effects on M1. The lasting effects are considered to be a kind of synaptic plasticity induction in cortical neurons. SICI is used to evaluate the M1 excitability state after these inductions. Conventional rTMS at 5 Hz enhances MEP size and reduces the amount of SICI. However, prolonged 5 Hz rTMS with 1800 pulses does not affect SICI, even though MEP is still enlarged. On the other hand, continuous theta burst stimulation (TBS) decreases both MEP and SICI. Another intervention method of paired associative stimulation (PAS) at interval of 25 ms induces MEP size enlargement without any changes in SICI. Quadri-pulse stimulation (QPS) does not affect SICI in either LTP or LTD like effect inductions. These results indicate that MEP changes by rTMS occur independently of changes in GABAergic inhibition. Those interventions could also induce synaptic plasticity in the cortical GABAergic inter-neuronal networks. However, neuro-plastic characters of M1 GABAergic inter-neuronal networks may be different from that of M1 excitatory neuronal networks. SICI could give us some more information about mechanisms for synaptic plasticity in M1.