期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 14, 页码 3879-3884出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1503252113
关键词
fMRI; neural network; VPS4A; dopamine receptor; GWAS
资金
- European Union FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) [LSHM-CT-2007-037286]
- FP7 Projects IMAGEMEND (Imaging Genetics for Mental Disorders) [602450]
- Multidisciplinary Approaches to Translational Research in Conduct Syndromes [603016]
- Innovative Medicine Initiative Project EU-AIMS [115300-2]
- Medical Research Council Grants (Developmental pathways into adolescent substance abuse) [93558, MR/N000390/1]
- Swedish funding agency FORMAS (Forskningsradet for Miljo, Areella naringar och Samhallsbyggande)
- National Institute for Research Biomedical Research Centre at South London
- Maudsley National Health Service Foundation Trust and King's College London
- Bundesministerium fur Bildung und Forschung [01GS08152, 01EV0711, SysAlc01ZX1311A]
- Forschungsnetz AERIAL
- NIH [R01 MH085772-01A1, T32 DA007290, R01AA019526, R21AA022404]
- NIH Consortium Grant - cross-NIH alliance [U54 EB020403]
- MRC [MR/N000390/1, G0901858] Funding Source: UKRI
- Medical Research Council [MC_PC_15018, G0901858, MR/N000390/1] Funding Source: researchfish
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.
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