Inter-individual Variation in the After-effect of Paired Associative Stimulation can be Predicted From Short-interval Intracortical Inhibition With the Threshold Tracking Method

Abstract 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 (PAS 25 ). 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 GABA A ergic activity in cortex, or on the proportion of late I-wave inputs that are evoked by TMS pulses during PAS 25 . Low levels of GABA facilitate LTP, whereas late I-waves are the site of facilitation after PAS 25 . Methods GABA A ergic inhibition was quantified using SICI measured with a threshold tracking method (SICI-TT) before and after PAS 25 in 18 healthy volunteers. Results The PAS 25 effect correlated with the level of SICI-TT ( r  = 0.6) before PAS 25 . Contrary to the GABA hypothesis, people who had good facilitation after PAS 25 had good inhibition measured by SICI-TT. On completion of the PAS 25 protocol, SICI-TT was reduced by an amount correlated with the size of the PAS 25 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 PAS 25 since this relies on facilitation of late I-waves.