Abstract summary 

Exercise is known to benefit motor skill learning in health and neurological disease. Evidence from brain stimulation, genotyping, and Parkinson's disease studies converge to suggest that the dopamine D2 receptor, and shifts in the cortical excitation and inhibition (E:I) balance, are prime candidates for the drivers of exercise-enhanced motor learning. However, causal evidence using experimental pharmacological challenge is lacking. We hypothesised that the modulatory effect of the dopamine D2 receptor on exercise-induced changes in the E:I balance would determine the magnitude of motor skill acquisition. To test this, we measured exercise-induced changes in excitation and inhibition using paired-pulse transcranial magnetic stimulation (TMS) in 22 healthy female and male humans, and then had participants learn a novel motor skill - the sequential visual isometric pinch task (SVIPT). We examined the effect of D2 receptor blockade (800 mg sulpiride) on these measures within a randomised, double-blind, placebo-controlled design. Our key result was that motor skill acquisition was driven by an interaction between the D2 receptor and E:I balance. Specifically, poorer skill learning was related to an attenuated shift in the E:I balance in the sulpiride condition, whereas this interaction was not evident in placebo. Our results demonstrate that exercise-primed motor skill acquisition is causally influenced by D2 receptor activity on motor cortical circuits. Exercise is known to benefit the ability to acquire new motor skills, but the neural mechanisms driving this phenomenon are not well understood. We tested whether the effects of exercise on cortical neurophysiology and motor skill learning was due to dopaminergic neuromodulation. We obtained measures of cortical excitation and inhibition before and after high-intensity cardiorespiratory exercise, and then had participants learn a novel motor skill. We provide causal evidence that motor skill acquisition is driven by an interaction between the dopamine D2 receptor and exercise-induced shifts in the cortical excitation:inhibition balance. Such findings have implications for prescribing exercise to improve motor learning in disorders of dopamine dysfunction, such as Parkinson's disease.

Authors & Co-authors:  Curtin Taylor Bellgrove Chong Coxon

Study Outcome 

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