Dopamine and DBS accelerate the neural dynamics of volitional action in Parkinson’s disease

Abstract

The ability to initiate volitional action is fundamental to human behavior. Loss of dopaminergic neurons in Parkinson’s disease (PD) is associated with impaired action initiation, also termed akinesia. Dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. We recorded invasive neural activity from both sensorimotor cortex and subthalamic nucleus (STN) in 25 PD patients performing self-initiated movements. Readiness potentials and brain signal decoding revealed long latencies between the neural representation of motor intention and execution. Dopamine and STN-DBS shortened these latencies, while shifting directional cortico-subthalamic oscillatory coupling from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms. Our study highlights a key role for dopamine and basal ganglia in the evolution of preparatory brain signals and orchestration of neural dynamics in encoding of volitional action.

Dopaminergic reinforcement in the motor system: Implications for Parkinson's disease and deep brain stimulation

“…Levodopainduced dyskinesia, the involuntary movements commonly seen as a side-effect of dopamine replacement therapy (Kwon et al, 2022), may provide a vivid image of a potential behavioural consequence of such an unspecific strengthening. from invasive brain signals (Köhler et al, 2023) could close the loop and act as a dopamine and basal ganglia neuroprosthetic (see Figure 4b). Here, machine learning methods, such as contrastive learning (Schneider et al, 2023), could be used to decode movement intention or presence from cortical activity and trigger stimulation (Merk et al, 2022(Merk et al, , 2023.…”