Wait and you shall see: sexual delay discounting in hypersexual Parkinson's disease.

The neurocomputational mechanisms underlying hypersexual impulse control disorder in Parkinson's disease remain poorly characterized. Using model-based fMRI and a delay-discounting paradigm, Girard et al. report that affected individuals show an increased willingness to wait to see erotic images, associated with altered engagement over anterior medial prefrontal cortex and striatum.Patients with Parkinsons disease may develop impulse control disorders under dopaminergic treatments. Impulse control disorders include a wide spectrum of behaviours, such as hypersexuality, pathological gambling or compulsive shopping. Yet, the neural systems engaged in specific impulse control disorders remain poorly characterized. Here, using model-based functional MRI, we aimed to determine the brain systems involved during delay-discounting of erotic rewards in hypersexual patients with Parkinsons disease (PD+HS), patients with Parkinsons disease without hypersexuality (PD HS) and controls. Patients with Parkinsons disease were evaluated ON and OFF levodopa (counterbalanced). Participants had to decide between two options: (i) wait for 1.5 s to briefly view an erotic image; or (ii) wait longer to see the erotic image for a longer period of time. At the time of decision-making, we investigated which brain regions were engaged with the subjective valuation of the delayed erotic reward. At the time of the rewarded outcome, we searched for the brain regions responding more robustly after waiting longer to view the erotic image. PD+HS patients showed reduced discounting of erotic delayed rewards, compared to both patients with Parkinsons disease and controls, suggesting that they accepted waiting longer to view erotic images for a longer period of time. Thus, when using erotic stimuli that motivate PD+HS, these patients were less impulsive for the immediate reward. At the brain system level, this effect was paralleled by the fact that PD+HS, as compared to controls and PD HS, showed a negative correlation between subjective value of the delayed reward and activity of medial prefrontal cortex and ventral striatum. Consistent with the incentive salience hypothesis combining learned cuereward associations with current relevant physiological state, dopaminergic treatment in PD+HS boosted excessive wanting of rewards and heightened activity in the anterior medial prefrontal cortex and the posterior cingulate cortex, as reflected by higher correlation with subjective value of the option associated to the delayed reward when ON medication as compared to the OFF medication state. At the time of outcome, the anterior medial prefrontal/rostral anterior cingulate cortex showed an interaction between group (PD+HS versus PD HS) and medication (ON versus OFF), suggesting that dopaminergic treatment boosted activity of this brain region in PD+HS when viewing erotic images after waiting for longer periods of time. Our findings point to reduced delay discounting of erotic rewards in PD+HS, both at the behavioural and brain system levels, and abnormal reinforcing effect of levodopa when PD+HS patients are confronted with erotic stimuli.