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

Abstract

Patients with Parkinson's 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 Parkinson's disease (PD+HS), patients with Parkinson's disease without hypersexuality (PD-HS) and controls. Patients with Parkinson's 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 delaye d 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 Parkinson's 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 th e 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 cue-reward 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.

Disrupted salience network dynamics in Parkinson's disease patients with impulse control disorders

“…In PD patients, temporal fluctuations in FC have been described as closely related to the severity of motor [15] and cognitive impairment [16,17], but its relation with impulsivity has not been studied. Given that previous static FC studies have shown that dopaminergic firing is able to alter limbic cortical signals to the VS, impairing the ability to change behavioral focus in response to change in stimulus salience [8,9,18], a dFNC approach may add relevant information as it represents the temporal changes of these connections [13]. For this reason, we hypothesized that PD-ICD patients would show specific dynamic functional connectivity (dFNC) changes in particular areas of the salience network/reward processing, possibly because these patients may continue to focus on those reward stimuli that have primarily induced the dopamine release, looping the cerebral areas implicated in hedonic evaluation of the stimulus and rewardbased decision making.…”

Functional Inhibitory Control Dynamics in Impulse Control Disorders in Parkinson's Disease

“…5,6 However, functional magnetic resonance imaging (fMRI) studies using reward-related tasks in PD patients with ICD (PD-ICD) have shown discrepant results; whereas 2 studies pointed toward diminished activation in the right VS, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC), 7,8 3 other studies showed higher activation in the VS, anterior prefrontal cortex (PFC), ACC, and OFC. [9][10][11] These discrepancies could be because of methodological factors, such as clinical differences in the PD populations studied (e.g., PD severity, ICD subtype, with or without treatment), the use of different rewardrelated tasks (e.g., related or unrelated to a specific ICD subtype), MRI imaging protocols, and analytical approaches. Moreover, although few studies have investigated functional connectivity (FC) during incentive-based tasks in PD-ICD patients, 12,13 the limited evidence available indicates mesolimbic pathway alterations and suggests ICDs in PD patients reflect disruptions beyond this pathway.…”

“…Confirming the role of dopamine as a reinforcement signal shaping future motivated behaviors, positron emission tomography studies focused on the dopaminergic system have indicated that ICDs in PD are associated with a higher release of dopamine in the ventral striatum (VS) during reward‐related tasks . However, functional magnetic resonance imaging (fMRI) studies using reward‐related tasks in PD patients with ICD (PD‐ICD) have shown discrepant results; whereas 2 studies pointed toward diminished activation in the right VS, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC), 3 other studies showed higher activation in the VS, anterior prefrontal cortex (PFC), ACC, and OFC . These discrepancies could be because of methodological factors, such as clinical differences in the PD populations studied (e.g., PD severity, ICD subtype, with or without treatment), the use of different reward‐related tasks (e.g., related or unrelated to a specific ICD subtype), MRI imaging protocols, and analytical approaches.…”

Measuring impulsivity in Parkinson’s disease: a correlational and structural neuroimaging study using different tests

“…[19] showed higher delay discounting in PD ICDs for financial rewards, Girard et al . [20] showed lower discounting in hypersexual PD ICDs for sexual rewards. Nonetheless, the most revealing conflicts come from studies evaluating several measures in the same sample.…”