Classical conditioning of faciliatory paired-pulse TMS

Abstract

In this proof-of-concept study, we questioned whether the influence of TMS on cortical excitability can be applied to classical conditioning. More specifically, we investigated whether the faciliatory influence of paired-pulse TMS on the excitability of the human motor cortex can be transferred to a simultaneously presented auditory stimulus through conditioning. During the conditioning phase, 75 healthy young participants received 170 faciliatory paired TMS pulses (1st pulse at 95% resting motor threshold, 2nd at 130%, interstimulus interval 12 ms), always presented simultaneously with one out of two acoustic stimuli. In the test phase, 20 min later, we pseudorandomly applied 100 single TMS pulses (at 130% MT), 50 paired with the conditioned tone—50 paired with a control tone. Using the Wilcoxon-Signed Rank test, we found significantly enhanced median amplitudes of motor evoked potentials (MEPs) paired with the conditioned tone as compared to the control tone, suggesting successful conditioning (p = 0.031, responder rate 55%, small effect size of r = − 0.248). The same comparison in only those participants with a paired-pulse amplitude < 2 mV in the conditioning phase, increased the responder rate to 61% (n = 38) and effect size to moderate (r = − 0.389). If we considered only those participants with a median paired-pulse amplitude < 1 mV, responder rate increased further to 79% (n = 14) and effect size to r = − 0.727 (i.e., large effect). These findings suggest increasingly stronger conditioning effects for smaller MEP amplitudes during paired-pulse TMS conditioning. These proof-of-concept findings extend the scope of classical conditioning to faciliatory paired-pulse TMS.

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“… 34 Depending on the intensity of conditioning stimulus (CS) and the test stimulus (TS) and ISI used, paired-pulse TMS is used to explore inhibitory or excitatory intracortical networks. 35 The short ISI (1–5 ms) with subthreshold CS and suprathreshold TS reaching 1.5 mV motor evoked potential (MEP) will produce short intracortical inhibition. 36 Reis et al 37 observed that increasing MEP amplitude with the ISI of 10–15 ms will produce a phenomenon known as intracortical facilitation.…”