The cholinergic system plays a key role in motor function, but whether pharmacological modulation of cholinergic activity affects motor sequence learning is unknown. The acetylcholine recepter antagonist biperiden, an established treatment in movement disorder, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double-blind placebo-controlled crossover design, we tested thirty healthy young participants and show that biperiden impairs the ability to learn sequential finger movements, accompanied by widespread oscillatory broadband power changes (4-25 Hz) in the motor sequence learning network after receiving biperiden, with greater power in the theta, alpha, and beta bands over ipsilateral motor and bilateral parietal–occipital areas. These findings highlight the role of cholinergic processes in motor sequence learning.Behavioral data (mean normalized learning score, reaction time difference, fatigue) for each participant, depending on condition (biperiden, placebo).Cluster-based permutation test results for the main effect sequence type (repeated, random), condition (biperiden, placebo), and their interaction and corresponding grand-average event-related spectral perturbations.

The cholinergic system plays a key role in motor function, but whether pharmacological modulation of cholinergic activity affects motor sequence learning is unknown. The acetylcholine recepter antagonist biperiden, an established treatment in movement disorder, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double-blind placebo-controlled crossover design, we tested thirty healthy young participants and show that biperiden impairs the ability to learn sequential finger movements, accompanied by widespread oscillatory broadband power changes (4-25 Hz) in the motor sequence learning network after receiving biperiden, with greater power in the theta, alpha, and beta bands over ipsilateral motor and bilateral parietal–occipital areas. These findings highlight the role of cholinergic processes in motor sequence learning.Behavioral data (mean normalized learning score, reaction time difference, fatigue) for each participant, depending on condition (biperiden, placebo).Cluster-based permutation test results for the main effect sequence type (repeated, random), condition (biperiden, placebo), and their interaction and corresponding grand-average event-related spectral perturbations.