Objective: To determine if a potential cause of apathy in Parkinson’s disease (PD) might be insensitivity to rewards, establish if this differentiates apathy from depression and investigate whether dopaminergic medication can enhance reward sensitivity.

Background: Apathy, a syndrome characterized by lack of motivation, is an under-recognised yet highly prevalent condition in PD. It significantly impacts upon quality of life, yet reliable objective clinical measures are lacking, often leading to a misdiagnosis of depression.

Methods: Two novel oculomotor paradigms were used to measure reward sensitivity. 51 healthy participants and 30 PD patients were assessed using Lille Apathy Rating Scale (LARS) and clinical depression scores. Saccades and pupil diameter were measured during presentation of monetary reward cues both ON and OFF dopaminergic medication. To distinguish between pupillary response to anticipated reward vs. response associated with motor preparation, a further 20 PD patients and 41 controls were tested on a Go/NoGo version of the task in which 50% of trials required no saccade to obtain reward. Controls also underwent diffusion-weighted MR imaging to explore neural correlates of pupillary reward sensitivity.

Results: Reward sensitivity, indexed by pupillary dilation for reward, was greater in controls and PD patients when ON compared to OFF (p<0.01). There was a significant correlation between pupil reward sensitivity and LARS scores in PD (p<0.001), with more apathetic individuals displaying less reward sensitivity. However, no such relationship was found for depression scores. The effect of dopaminergic medication on reward sensitivity varied with severity of apathy. Importantly, pupillary reward sensitivity was observed regardless of whether a saccade was required (Go/NoGo task) confirming this effect is not due to eye movement preparation. In controls, reward sensitivity correlated with fractional anisotropy value in the caudal cingulate zone (p<0.05), an area implicated in motivation.

Conclusions: Reward insensitivity may underlie apathy – but not depression – in PD and is quantifiable using pupillary responses to upcoming rewards, independent of motor preparation. Dopaminergic medication can enhance reward sensitivity and may therefore be an effective therapy for apathy, independent of its effects on motor control.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reward-insensitivity-differentiates-apathy-from-depression-in-parkinsons-disease/