Shared pathway-specific network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson’s disease

Deep brain stimulation is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinson’s disease, subthalamic deep brain stimulation clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex – basal ganglia networks are unknown. To address this critical knowledge gap, we combined fully invasive neural multisite recordings in patients undergoing deep brain stimulation surgery with normative MRI-based whole-brain connectomics. Our findings demonstrate that dopamine and stimulation exert distinct mesoscale effects through modulation of local neural population activity. In contrast, at the macroscale, stimulation mimics dopamine in its suppression of excessive interregional network synchrony associated with indirect and hyperdirect cortex – basal ganglia pathways. Our results provide a better understanding of the circuit mechanisms of dopamine and deep brain stimulation, laying the foundation for advanced closed-loop neurostimulation therapies.