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 (CS 1 and CS 2) 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 CS single alone had no effect on the test MEP, but with two CS, clear inhibition was elicited at certain intervals. With a CS 2-TS interval of 2 ms, maximum suppression occurred if CS 1 was applied 1–2.5 ms before CS 2. This inhibitory effect tapered off gradually as the CS 2-CS 1 interval was increased up to 13 ms. When facilitation was present with a CS single-TS interval of 10 ms, a small but non-significant extra-facilitation occurred at ISIs between CS 2 and CS 1 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.