title: 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.
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, Magdeburg 39118 , Germany.
authors.forename: Björn H
authors.initials: BH
authors.lastname: Schott
authors.forename: Ludwig
authors.initials: L
authors.lastname: Niehaus
authors.forename: Bianca C
authors.initials: BC
authors.lastname: Wittmann
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schütze
authors.forename: Constanze I
authors.initials: CI
authors.lastname: Seidenbecher
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.forename: Emrah
authors.initials: E
authors.lastname: Düzel
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology* / Q000523:psychology; D001245:Association Learning; D001931:Brain Mapping / Q000379:methods; D003463:Cues; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008032:Limbic System / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008636:Mesencephalon / Q000503:physiopathology; D008875:Middle Aged; D010300:Parkinson Disease / Q000503:physiopathology* / Q000523:psychology; D011930:Reaction Time; D012201:Reward