Apathy blunts neural response to money in Parkinson's disease

Abstract

Apathy, defined as a primary deficit in motivation and manifested by the simultaneous diminution in the cognitive and emotional concomitants of goal-directed behavior, is a common and debilitating non-motor symptom of Parkinson's disease (PD). Despite the high prevalence and clinical significance of apathy, little is known about its pathophysiology, and in particular how apathy relates to alterations in the neural circuitry underpinning the cognitive and emotional components of goal-directed behavior. Here, we examined the neural coding of reward cues in patients with PD, with or without clinically significant levels of apathy, during performance of a spatial search task during H₂ ¹⁵O PET (positron emission tomography) functional neuroimaging. By manipulating search outcome (money reward vs valueless token), while keeping the actions of the participants constant, we examined the influence of apathy on the neural coding of money reward cues. We found that apathy was associated with a blunted response to money in the ventromedial prefrontal cortex, amygdala, striatum, and midbrain, all part of a distributed neural circuit integral to the representation of the reward value of stimuli and actions, and the influence of reward cues on behavior. Disruption of this circuitry potentially underpins the expression of the various manifestations of apathy in PD, including reduced cognitive, emotional, and behavioral facets of goal-directed behavior.

Keywords:

• Amygdala
• Depression
• Dopamine
• Incentive salience
• Ventromedial prefrontal cortex

Acknowledgments

We thank all volunteers for their participation and the clinical, chemistry, radiography, and instrumentation staff of the Cyclotron Unit, Hammersmith Hospital, for their contributions. This work was supported by Parkinson's UK. I.K.G. was supported by a Parkinson's UK prize studentship and the Richard-Winter-Stiftung. The Wales Institute of Cognitive Neuroscience supports A.D.L.

Notes

¹ A similar ANCOVA, controlling for MMPD, produced identical results.