Influence of isometric muscle contraction before and during paired associative stimulation

Introduction: We previously showed that voluntary isometric contraction of sufficient duration before application of a Theta-Burst-Stimulation protocol known to induce enhancement of cortical excitability reversed the direction of induced plasticity (Gentner et al 2008). Here we examined the influence of isometric muscle contraction before and during paired associative stimulation (PAS), another plasticity-inducing TMS protocol.

Methods: 12 healthy subjects (6 women, aged 18 – 25 years, mean 22 ± 2 years, all right-handed) were investigated with PAS (repetitive combination of electric stimulation of the right median nerve (0.1 Hz, 90 pulses) with TMS delivered subsequently at 25 ms to the contralateral motor cortex) in five different sessions. Continuous isometric muscle contraction was performed for 0 s (ACT0; Expt.1), 90 s (ACT90; Expt. 2) or 300 s (ACT300; Expt. 3) before PAS. In Expt. 4, muscle contraction was performed for a total duration of 300 s during PAS (1 s after the TMS pulse for 3.4 s in every interval, APAS300), in Expt. 5 this action was performed passively by the investigator (PMPAS300). In the pre-PAS activation conditions (Expt. 1 – 3) corticospinal excitability was probed by measuring the peak-to-peak amplitude of motor evoked potentials elicited in the abductor pollicis brevis muscle before and after muscle activiation and up to 32 min following PAS. In the during-PAS activation condition, MEPs were measured before and following PAS.

Results:. Following the different PAS variants corticospinal excitability changed as a function of the way of activation (ANOVA time*intervention, p < 0.001). MEP amplitudes temporarily increased following ACT90 ("post-exercise facilitation") and decreased following ACT300 ("post-exercise depression"), respectively. Compared to baseline, excitability increased after PAS-ACT0 (+81%), PAS-ACT90 (+87%) and PAS-ACT300 (+52%). Active muscle contraction during PAS (APAS300) resulted in a decrease of corticospinal excitability (-18%), whereas passive activation (APAS300) did not change the polarity of the PAS-effect (increase up to +71%).

Discussion: PAS-induced long-term potentiation-like plasticity is reversed to depression by muscle contraction, but not afferent stimulation alone, applied immediately before the PAS pulses. This phenomenon provides a new type of modulating plasticity that appears to be distinct from action-induced metaplasticity by attended repetitive activation before the PAS intervention period.

References: Gentner et al., Cereb Cortex. 2008 Sep;18(9):2046 – 53.