Late Cortical Disinhibition in Human Motor Cortex: A Triple-Pulse Transcranial Magnetic Stimulation Study

Cash RFH, Ziemann U, Murray K, Thickbroom GW. Late cortical disinhibition in human motor cortex: a triple-pulse transcranial magnetic stimulation study. J Neurophysiol 103: 511-518, 2010. First published November 18, 2009; doi: 10.1152/jn.00782.2009. In human motor cortex transcranial magnetic stimulation (TMS) has been used to identify short-interval intracortical inhibition (SICI) corresponding to gamma-aminobutyric acid type A (GABA(A)) effects and long-interval intracortical inhibition (LICI) and the cortical silent period (SP) corresponding to postsynaptic GABA(B) effects. Presynaptic GABA(B) effects, corresponding to disinhibition, can also be identified with TMS and have been shown to be acting during LICI by measuring SICI after a suprathreshold priming stimulus (PS). The duration of disinhibition is not certain and, guided by studies in experimental preparations, we hypothesized that it may be longer-lasting than postsynaptic inhibition, leading to a period of late cortical disinhibition and consequently a net increase in corticospinal excitability. We tested this first by measuring the motor-evoked potential (MEP) to a test stimulus (TS), delivered after a PS at interpulse intervals (IPIs) <= 300 ms that encompassed the period of PS-induced LICI and its aftermath. MEP amplitude was initially decreased, but then increased at IPIs of 190-210 ms, reaching 160 +/- 17% of baseline 200 ms after PS (P < 0.05). SP duration was 181 +/- 5 ms. A second experiment established that the onset of the later period of increased excitability correlated with PS intensity (r(2) = 0.99) and with the duration of the SP (r(2) = 0.99). The third and main experiment demonstrated that SICI was significantly reduced in strength at all IPIs <= 220 ms after PS. We conclude that TMS-induced LICI is associated with a period of disinhibition that is at first masked by LICI, but that outlasts LICI and gives rise to a period during which disinhibition predominates and net excitability is raised. Identification of this late period of disinhibition in human motor cortex may provide an opportunity to explore or modulate the behavior of excitatory networks at a time when inhibitory effects are restrained.