Inhibitory interactions between pairs of subthreshold conditioning stimuli in the human motor cortex

Objective: These experiments examined short interval paired-pulse paradigms for intracortical inhibition (ICI) and facilitation (ICF). We tested whether pairs of subthreshold conditioning stimuli interact, and whether they showed rapid periodicity similar to that observed in subthreshold I-wave interaction. Methods: Transcranial magnetic stimulation (TMS) was given over left M1 to evoke a motor-evoked potential (MEP) of approximately 1 mV peak-to-peak amplitude in the contralateral first dorsal interosseous (FDI) muscle. Each test shock (TS) was preceded by single or paired subthreshold conditioning stimuli (CS1 and CS2) at short interstimulus intervals (ISIs 1–15 ms). Intensities of CS were set just below thresholds for intracortical inhibition (ICI) or intracortical facilitation (ICF). Results: Each CSsingle alone had no effect on the test MEP, but with two CS, clear inhibition was elicited at certain intervals. With a CS2-TS interval of 2 ms, maximum suppression occurred if CS1 was applied 1–2.5 ms before CS2. This inhibitory effect tapered off gradually as the CS2-CS1 interval was increased up to 13 ms. When facilitation was present with a CSsingle-TS interval of 10 ms, a small but non-significant extra-facilitation occurred at ISIs between CS2 and CS1 of 6–15 ms. Conclusions: Two subthreshold conditioning stimuli facilitate inhibition that lacks the rapid periodicity typical of I-wave interaction. The data would be compatible with a model in which synaptic inputs converge on a common inhibitory interneurone.