Neural basis of reward anticipation and its genetic determinants

Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):3879-84. doi: 10.1073/pnas.1503252113. Epub 2016 Mar 21.


Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.

Keywords: GWAS; VPS4A; dopamine receptor; fMRI; neural network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adolescent
  • Alcohol Drinking / psychology
  • Animals
  • Anticipation, Psychological / physiology*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Brain Mapping*
  • Child
  • Corpus Striatum / physiopathology*
  • Drosophila
  • Endosomal Sorting Complexes Required for Transport / genetics*
  • Female
  • Forecasting
  • Genome-Wide Association Study
  • Haplotypes / genetics
  • Humans
  • Male
  • Motivation
  • Neuropsychological Tests
  • Reward*
  • Vacuolar Proton-Translocating ATPases / genetics*


  • Endosomal Sorting Complexes Required for Transport
  • Vacuolar Proton-Translocating ATPases
  • ATPases Associated with Diverse Cellular Activities
  • VPS4A protein, human