Introduction
gain of motor circuits, voluntary muscle contraction, muscle fatigue, voluntary muscle contractions
CONTRACTION, CORTEX
Four primary neuromodulator systems exist in the central nervous system (CNS): dopaminergic, adrenergic, serotonergic, and cholinergic. While there is a good understanding of how the first three systems regulate the gain of motor circuits in the CNS, our understanding of how the cholinergic system regulates the excitability of motor pathways during voluntary muscle contraction is limited. Muscarinic acetylcholine receptors (mAChRs) are the predominant cholinergic receptor in the CNS, where activation of mAChRs initiates G-protein–coupled signal transduction pathways (Caulfield The use of atropine for the insight of anti-muscarinic effects within human studies has been vastly used, however, promethazine allows the same insight without as considerable side-effects. Promethazine is one of the most potent antihistaminergic drugs with obvious antimuscarinic and sedative effects (Cantisani et al. Transcranial magnetic stimulation (TMS) is a non-invasive tool that can be used to assess the excitability of cortical circuits and motor pathways in humans. A single TMS pulse applied to the motor representation of a muscle induces a motor evoked potential (MEP) in the target muscle. The amplitude of the MEP reflects the excitability of the corticospinal pathway, where facilitation of MEP responses progressively increases until 50–70% MVC for upper limb muscles (Taylor et al. The purpose of this study was to assess if muscarinic receptor blockade modulates TMS-evoked MEPs and SPs during voluntary muscle contractions. The target muscle in this study was the biceps brachii, where EMG responses to single TMS pulses were recorded during elbow flexions of 10%, 25%, 50%, 75%, and 100% of MVC. To determine if muscarinic receptors have a neuromodulatory role when the motor system is fatigued, the range of contraction intensities were again examined. However, this time they were preceded by a sustained maximal effort elbow flexion that reduced the individuals force generating capacity to 60% of their initial MVC. It was hypothesised that a mAChR blockade would increase biceps brachii MEP area, and lengthen biceps brachii SP, during the voluntary elbow flexions regardless of whether muscle fatigue was present. Moreover, it was hypothesized that these antimuscarinic effects would be most prominent during higher contraction intensities when voluntary drive from the motor cortex to the target muscle is high.