The effects of alterations in conditioning stimulus intensity on short interval intracortical inhibition

Short interval intracortical inhibition [SICI] is mediated by cortical inhibitory interneurons, with two physiologically distinct phases at interstimulus interval [ISI]<1 ms and 2.5-3 ms. The second phase of SICI is mediated by synaptic mechanisms, while the first phase has been attributed to axonal refractoriness, synaptic mechanisms or both. In the present study, threshold-tracking transcranial magnetic stimulation was used to explore mechanisms underlying SICI. SICI was studied in 10 normal subjects at three different conditioning stimulus [CS] intensities [40%, 70% and 90% of resting motor threshold, RMT, defined as the threshold for a MEP of approximately 0.2 mV]. Motor responses were recorded from abductor pollicis brevis. Maximal SICI developed with CS set to 70% RMT [SICI(70%)], with two phases evident, at ISI 1 ms [12.7+/-3.4%] and ISI 2.5 ms [19.3+/-2.9%]. With CS set to 40% RMT, SICI occurred between 1 ms and 5 ms, peaking at 2.5 ms and was reduced [1.9+/-1.4%, P<0.0001] compared to peak SICI(70%). The small SICI peak at 1 ms was absent. With CS at 90% RMT, SICI developed between 2 and 5 ms, peaking at 4 ms [11.2+/-7.8%]. Facilitation was evident at 1 ms. The findings from the present study suggest that inhibitory circuits with different thresholds underlie the phases of SICI, with synaptic mechanisms also critical to the development of SICI at 1 ms.