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

Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion, often attributed to changes in striatal dopamine function. Understanding how dopamine signaling in the striatum and basal ganglia shapes human behavior is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large scale brain networks and many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, whether dopamine signals in the basal ganglia serve an overarching computational principle which could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing, or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson’s disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition, as defined by the sequence effect or decrement of movement. Finally, we speculate on how therapeutic interventions such as deep brain stimulation (DBS) may be able to reinstate reinforcement signals and thereby improve treatment strategies of PD in the future.