Cholinergic modulation of motor sequence learning

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 receptor antagonist biperiden, an established treatment in movement disorders, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double-blind placebo-controlled crossover design, we tested 30 healthy young participants and showed 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. The reduced early theta power during a repeated compared with random sequence, likely reflecting disengagement of top-down attention to sensory processes, was disrupted by biperiden. Alpha synchronization during repeated sequences reflects sensory gating and lower visuospatial attention requirements compared with visuomotor responses to random sequences. After biperiden, alpha synchronization was greater, potentially reflecting excessive visuospatial attention reduction, affecting visuomotor responding required to enable sequence learning. Beta oscillations facilitate sequence learning by integrating visual and somatosensory inputs, stabilizing repeated sequences and promoting prediction of the next stimulus. The beta synchronization after biperiden fits with a disruption of the selective visuospatial attention enhancement associated with initial sequence learning. These findings highlight the role of cholinergic processes in motor sequence learning.