Muscarinic receptor blockade causes post-contraction enhancement in corticospinal excitability following maximal contractions

Abstract

Although synaptic transmission in motor pathways can be regulated by neuromodulators such as acetylcholine, few studies have examined how cholinergic activity affects cortical and spinal motor circuits following muscle contractions of varying intensities. Methods: This study was a human, double-blinded, placebo-controlled, crossover design. Participants attended two testing sessions where they were administered either a placebo or 25 mg of promethazine. Electromyography of the abductor digiti minimi (ADM) was measured for all conditions. Motor evoked potentials (MEPs) were obtained via motor cortical transcranial magnetic stimulation (TMS), and F waves were obtained via ulnar nerve electrical stimulation. MEPs and F waves were examined 1) when the muscle was at rest, 2) after the muscle had been active, and 3) after the muscle had been fatigued. Results: MEPs were unaffected by muscarinic receptor blockade when measurements were recorded from the resting muscle or following a 50% isometric maximal voluntary contraction (MVC). However, muscarinic receptor blockade increased MEP area following a 10 s MVC (p = 0.019) and following a fatiguing 60 s MVC (p = 0.040). F wave area and persistence were not affected by promethazine for any muscle contraction condition. Conclusions: Corticospinal excitability was heavily influenced by cholinergic effects when voluntary drive to the muscle was high. Given that spinal motoneurone excitability remained unaffected by the receptor blockade for any task, it appears that cholinergic effects were restricted to the cortex strong during muscle contractions.