Impaired value-based decision-making in Parkinson's disease apathy

作者：Gilmour W, Mackenzie G, Feile M, Tayler-Grint L, Suveges S, Macfarlane JA, Macleod AD, Marshall V, Grunwald IQ, Steele JD, Gilbertson T · 发表于：Brain : a journal of neurology · 年份：2024 · DOI：10.1093/brain/awae025 · 研究领域：Parkinson’s disease、apathy、computational modelling、decision-making、functional MRI、reward insensitivity

Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects of motivated decision-making. Specifically, these neuromodulators have overlapping contributions to encoding the value of decisions, and influence whether to explore alternative courses of action or persist in an existing strategy to achieve a rewarding goal. Building upon this work, we hypothesized that apathy in Parkinson's disease should be associated with an impairment in value-based learning. Using a four-armed restless bandit reinforcement learning task, we studied decision-making in 75 volunteers; 53 patients with Parkinson's disease, with and without clinical apathy, and 22 age-matched healthy control subjects. Patients with apathy exhibited impaired ability to choose the highest value bandit. Task performance predicted an individual patient's apathy severity measured using the Lille Apathy Rating Scale (R = -0.46, P < 0.001). Computational modelling of the patient's choices confirmed the apathy group made decisions that were indifferent to the learnt value of the options, consistent with previous reports of reward insensitivity. Further analysis demonstrated a shift aw...