title: Dopamine restores reward prediction errors in old age.
abstract: Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, UK. rumana.neuro@gmail.com
authors.forename: Rumana
authors.initials: R
authors.lastname: Chowdhury
authors.forename: Marc
authors.initials: M
authors.lastname: Guitart-Masip
authors.forename: Christian
authors.initials: C
authors.lastname: Lambert
authors.forename: Peter
authors.initials: P
authors.lastname: Dayan
authors.forename: Quentin
authors.initials: Q
authors.lastname: Huys
authors.forename: Emrah
authors.initials: E
authors.lastname: Düzel
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dolan
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000470:Alkaloids; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D012054:Reinforcement, Psychology; D012201:Reward; D013997:Time Factors; D055815:Young Adult
chemical_list: D000470:Alkaloids; D015259:Dopamine Agents; C110131:Wilcox compound; D007980:Levodopa; D010100:Oxygen