Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity.

Paired transcranial magnetic stimulation has greatly advanced our understanding of the mechanisms which control excitability in human motor cortex. While it is clear that paired-pulse excitability depends on the exact interstimulus interval (ISI) between the first (S1) and second stimulus (S2), relatively little is known about the effects of the intensities of S1 and S2, and the effects of manipulating neurotransmission through the GABA(A) receptor. When recording the motor evoked potential (MEP) from the resting abductor digiti minimi (ADM) muscle, using a fixed ISI of 1.5 ms, and expressing the interaction between S1 and S2 as MEP(S1+S2)/(MEP(S1) + MEP(S2)), then a systematic variation of the intensities of S1 and S2 revealed short-interval intracortical facilitation (SICF) if S1 and S2 were approximately equal to MEP threshold (RMT), or if S1 > RMT and S2 < RMT. In contrast, short-interval intracortical inhibition (SICI) occurred if S1 < RMT and S2 > RMT. Contraction of the ADM left SICI unchanged but reduced SICF. The GABA(A) receptor agonist diazepam increased SICI and reduced SICF in the resting ADM while diazepam had no effect during ADM contraction. Surface EMG and single motor unit recordings revealed that during ADM contraction SICI onset was at the I3-wave latency of S2, whereas SICF typically "jumped up" by one I-wave and started with the I2-wave latency of S2. Findings suggest that SICI is mediated through a low-threshold GABA(A) receptor-dependent inhibitory pathway and summation of IPSP from S1 and EPSP from S2 at the corticospinal neurone. In contrast, SICF originates through non-synaptic facilitation at the initial axon segment of interneurones along a high-threshold excitatory pathway.