Ageing and early-stage Parkinson's disease affect separable neural mechanisms of mesolimbic reward processing

Abstract

The ability to learn stimulus-reward associations on the basis of reward prediction errors critically depends on the mesolimbic dopaminergic system including the dopaminergic midbrain and the ventral striatum. It is known that healthy elderly and patients with Parkinson's disease are less proficient than healthy young adults in learning stimulus-reward contingencies, but it is unclear whether this is due to dysfunctional mesolimbic reward prediction or due to deficiency in processing the rewards per se. We used a well-established event-related fMRI reward-prediction paradigm to address this question. Young adults showed the well-replicated pattern of midbrain and ventral striatal activation for stimuli that predicted monetary reward when compared with stimuli that predicted neutral feedback. Also, as expected, the predicted reward feedback itself did not elicit a mesolimbic response. Healthy elderly subjects and unmedicated early-stage idiopathic Parkinson's disease patients showed the opposite pattern with an absent mesolimbic reward prediction response, but mesolimbic activation to the reward feedback itself. This suggests that the healthy elderly and Parkinson's disease patients were less proficient in learning the predictive value of the reward cues despite preserved mesolimbic processing of reward prediction errors. Parkinson's disease patients additionally displayed a relatively increased response of the anterior cingulate during reward feedback processing and diminished functional connectivity of the midbrain and ventral striatum. Our results are compatible with existing behavioural evidence that both groups exhibit a particularly pronounced deficit in learning from positive feedback and support the view that a tendency to underestimate expected values of reward cues might underlie this deficit. Furthermore, alterations in reward processing in Parkinson's disease extend beyond accelerated ageing effects and include altered connectivity within the mesolimbic system.

Dopamine Agonists Diminish Value Sensitivity of the Orbitofrontal Cortex: A Trigger for Pathological Gambling in Parkinson's Disease?

“…In fact, one might not assume this relationship to be maintained in PD. A recent neuroimaging study in PD patients after withdrawal of medication, elderly and young healthy controls showed that though RPE processing seems relatively preserved, PD patients and elderly controls show a markedly impaired reward prediction signal (Schott et al, 2007). Given the subtle nature of this relationship in young participants, the relative loss of this relationship in elderly and PD van Eimeren et alpatients, and the lack of such a relationship in our study, we assume that a putative influence can only be of negligible quantity.…”

Functional Connectivity of the Striatum Links Motivation to Action Control in Humans

“…To investigate the relationship between the neural response during reward anticipation versus no reward anticipation and the behavioral benefit in the rewarded relative to the neutral condition, we computed the relative reaction time (RT) advantages as [(RT no reward Ϫ RT reward )/RT no reward ] for all subjects, in line with common definitions (Schott et al, 2007). Accordingly, we computed the behavioral benefit from specific oculomotor preparation as [(RT neutral prep Ϫ RT spec prep )/RT neutral prep ].…”

Decision Making Across the Life Span

“…However, some functional neuroimaging studies have examined brain activity in the striatum, a target region for midbrain dopaminergic neurons (Lyndbalta and Haber, 1994). Such studies have found that older adults show robust responses in ventral and/or dorsal striatum to positive outcomes (Schott et al, 2007;Samanez-Larkin et al, 2010). Results from studies examining reward anticipation are more mixed, with older adults showing less ventral striatal activation than younger adults in some cases (Schott et al, 2007; but not in all studies .…”

“…Such studies have found that older adults show robust responses in ventral and/or dorsal striatum to positive outcomes (Schott et al, 2007;Samanez-Larkin et al, 2010). Results from studies examining reward anticipation are more mixed, with older adults showing less ventral striatal activation than younger adults in some cases (Schott et al, 2007; but not in all studies . There are also age differences in whether stronger responses to outcomes are seen early or late in the learning phase of a probabilistic learning task .…”