Sub-second Dopamine Signals during Risky Decision-Making in Patients with Impulse Control Disorder

Abstract

AbstractBackgroundImpulse Control Disorder (ICD) in Parkinson’s disease is a behavioral addiction arising secondary to dopaminergic therapies, most often dopamine receptor agonists. Prior research implicates changes in striatal function and heightened dopaminergic activity in the dorsal striatum of patients with ICD. However, this prior work does not possess the temporal resolution required to investigate dopaminergic signaling during real-time progression through various stages of decision-making involving anticipation and feedback.MethodsWe recorded high-frequency (10Hz) measurements of extracellular dopamine in the striatum of patients with (N=3) and without (N=3) a history of ICD secondary to dopamine receptor agonist therapy for Parkinson’s disease symptoms. These measurements were made using carbon fiber microelectrodes during awake DBS neurosurgery and while participants performed a sequential decision-making task involving risky investment decisions and real monetary gains and losses. Per clinical standard-of-care, participants withheld all dopaminergic medications prior to the procedure.ResultsPatients with ICD invested significantly more money than patients without ICD. On each trial, patients with ICD made smaller adjustments to their investment levels compared to patients without ICD. In patients with ICD, dopamine levels rose or fell on sub-second timescales in anticipation of investment outcomes consistent with increased or decreased confidence in a positive outcome, respectively; dopamine levels in patients without ICD were significantly more stable during this phase. After outcome revelation, dopamine levels in patients with ICD rose significantly more than in inpatients without ICD for better-than-expected gains. For worse-than-expected losses, dopamine levels in patients with ICD remained level whereas dopamine levels in patients without ICD fell.ConclusionWe report significantly increased risky behavior and exacerbated phasic dopamine signaling, on sub-second timescales, anticipating and following the revelation of the outcomes of risky decisions in patients with ICD. Notably, these results were obtained when patients who had demonstrated ICD in the past but were, at the time of surgery, in an off-medication state. Thus, it is unclear whether observed signals reflect an inherent predisposition for ICD that was revealed when dopamine receptor agonists were introduced or whether these observations were caused by the introduction of dopamine receptor agonists and the patients having experienced ICD symptoms in the past. Regardless, future work investigating dopamine’s role in human cognition, behavior, and disease should consider the signals this system generates on sub-second timescales.