Dopamine agonist treatment increases sensitivity to gamble outcomes in the hippocampus in de novo Parkinson’s disease

BACKGROUND: Parkinson’s disease is associated with severe nigro-striatal dopamine depletion, leading to motor dysfunction and altered reward processing. We previously showed that drug-naïve patients with Parkinson’s disease had a consistent attenuation of reward signalling in the mesolimbic and mesocortical system. Here, we address the neurobiological effects of dopaminergic therapy on reward sensitivity in the mesolimbic circuitry, and how this may contribute to neuropsychiatric symptoms. OBJECTIVES: We tested the hypothesis that (1) dopaminergic treatment would restore the attenuated, mesolimbic and mesocortical responses to reward; and (2) restoration of reward responsivity by dopaminergic treatment would predict motor performance and the emergence of impulse control symptoms. METHODS: In 11 drug-naïve Parkinson patients, we prospectively assessed treatment-induced changes in reward processing before, and eight weeks after initiation of monotherapy with dopamine agonists. They were compared to 10 non-medicated healthy controls who were also measured longitudinally. We used whole-brain functional magnetic resonance imaging at 3 Tesla to assess the reward responsivity of the brain to monetary gains and losses, while participants performed a simple consequential gambling task. RESULTS: In patients, dopaminergic treatment improved clinical motor symptoms without significantly changing task performance. Dopamine agonist therapy induced a stronger reward responsivity in the right hippocampus with higher doses being less effective. None of the patients developed impulse control disorders in the follow-up period of four years. CONCLUSIONS: Short-term treatment with first-ever dopaminergic medication partially restores deficient reward-related processing in the hippocampus in de novo Parkinson’s disease.