Neural reinforcement learning signals predict recovery from impulse control disorder symptoms in Parkinson's disease.

ABSTRACT

BACKGROUND: Impulse control disorders (ICD) in Parkinson's disease (PD) are associated with a heavy burden on patients and caretakers. While recovery can occur, ICD persists in many patients despite optimal management. The basis for this inter-individual variability in recovery is unclear and poses a major challenge to personalized health care. METHODS: We adopt a computational psychiatry approach and leverage the longitudinal, prospective Personalized Parkinson Project (N=136 persons with PD, within 5 years of diagnosis) to combine dopaminergic learning theory-informed fMRI with machine learning (at baseline) to predict ICD symptom recovery after two years of follow-up. We focused on a change in QUIP-rs across the entire cohort, regardless of an ICD diagnosis. RESULTS: Greater reinforcement learning signals during gain trials but not loss trials at baseline, including those in the ventral striatum, medial prefrontal cortex and the behavioral accuracy score measured while ON medication were associated with greater recovery from impulse control symptoms two years later. These signals accounted for a unique proportion of the relevant variability over and above that explained by other known factors, such as decreases in dopamine agonist use. CONCLUSIONS: Our results provide a proof of principle for combining generative model-based inference of latent learning processes with machine learning-based predictive modeling of variability in clinical symptom recovery trajectories. Hence, we showed that RL modelling parameters predict recovery from ICD symptoms in PD.