Motor learning leverages coordinated low-frequency cortico-basal ganglia activity to optimize motor preparation in humans with Parkinson's disease.

Learning dexterous motor sequences is crucial to autonomy and quality of life but can be altered in Parkinson's disease (PD). Learning involves optimizing pre-movement planning (preplanning) of multiple sequence elements to reduce computational overhead during active movement. However, it is unclear which brain regions mediate preplanning or how this process evolves with learning. Recording cortico-basal ganglia field potentials during a multi-day typing task in four individuals with PD, we found evidence for network-wide multi-element preplanning that improved with learning, facilitated by functional connectivity. In both cortex and basal ganglia, pre-movement gamma (, 30-250 Hz) activity, historically linked to population spiking, distinguished between future action sequences and became increasingly predictive with learning. For motor cortex , this increase was tied to learning-related cross-frequency coupling led by cortically-driven network delta (, 0.5-4 Hz) synchrony. More generally, coordinated network supported a complex pattern of learning-driven cross-frequency couplings within and between cortex and basal ganglia, including striatal lead of cortical beta (, 12-30 Hz) activity, reflecting the specialized roles of these brain regions in motor preparation. In contrast, impaired learning was characterized by practice-driven decreases in 's predictive value, limited cross-frequency coupling and absent network synchrony, with network dynamics possibly altered by pathologically high inter-basal ganglia synchrony. These results suggest that cortically-led phase coordination optimized cortico-basal ganglia multi-element preplanning through enhanced recruitment of higher-frequency neural activity. Neurostimulation that enhances cortico-basal ganglia synchrony may thus hold potential for improving skilled fine motor control in PD.