Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder
Open accessAbstract
Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P<0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD.
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Only remitters and controls presented significant psycho-physiological interaction between fronto-striatal reward and outcome valence networks, and there was evidence for compensatory activation in left prefrontal regions in remitters.
“However, only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks and there was evidence for compensatory activation in left prefrontal regions in the remitters (Wetterling et al., 2015).”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Wetterling et al., 2015
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- Authors
- Wetterling, F., McCarthy, H., Tozzi, L., Skokauskas, N., O'Doherty, J. P., Mulligan, A., Meaney, J., Fagan, A. J., Gill, M., & Frodl, T.
- Affiliations
- Trinity College Dublin (IE)
- Norwegian University of Science and Technology (NO)
- Division of the Humanities and Social Sciences and Computation and Neural Systems Program California Institute of Technology Pasadena California
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2015-08-19
- Volume
- 36
- Issue
- 11
- Pages
- 4648-4663
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6869504
- OpenAlex
- W2141254296
- Cited by
- 20
- References
- 32
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 1 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 3
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- Health Research Board (H01421)
- Science Foundation (Stokes Professorship grant) (G20330)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, persistent ADHD, reward processing, medial prefrontal cortex, striatum, reversal learning, outcome valence, fronto-striatal network, compensatory strategies, antisocial behavior, adult ADHD
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Probability Learning, Reward, Neostriatum, Prefrontal Cortex, Young Adult
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