Inter-individual variation in the after-effect of paired associative stimulation can be predicted from short-interval intracortical inhibition with the threshold tracking method

Background: Paired associative stimulation (PAS), which is used to test a long term potentiation (LTP)-like effect, involves repeated pairing of peripheral somatosensory input with transcranial magnetic stimulation (TMS) given 25 ms later over M1 (PAS25). The effect is usually quantified as an increase in amplitude of motor evoked potentials evoked by single pulse TMS. However, the effect varies greatly between individuals.

Objective/hypothesis: We hypothesized that variability depends on either the individual level of GABAAergic activity in cortex, or on the proportion of late I-wave inputs that are evoked by TMS pulses during PAS25. Low levels of GABA facilitate LTP, whereas late I-waves are the site of facilitation after PAS25.

Methods: GABAAergic inhibition was quantified using SICI measured with a threshold tracking method (SICI-TT) before and after PAS25 in 18 healthy volunteers.

Results: The PAS25 effect correlated with the level of SICI-TT (r = 0.6) before PAS25. Contrary to the GABA hypothesis, people who had good facilitation after PAS25 had good inhibition measured by SICI-TT. On completion of the PAS25 protocol, SICI-TT was reduced by an amount correlated with the size of the PAS25 effect (r = 0.5-0.6 at an interstimulus interval of 2.5-3.0 ms).

Conclusions: SICI is known to target late I-waves, thus SICI-TT will depend on the proportion of late I-waves evoked by the TMS test pulse. If the pulse recruits a large fraction of late I-waves, individuals will show good SICI-TT; they will also respond well to PAS25 since this relies on facilitation of late I-waves.