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Cited by 108Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings

Open access
von Rhein, Daniel, Cools, Roshan, Zwiers, Marcel P., van der Schaaf, Marieke, Franke, Barbara, Luman, Marjolein, Oosterlaan, Jaap, Heslenfeld, Dirk J. +8 more·2015·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2015.02.012PMC PMC4417499
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Abstract

Objective Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is not known whether reward processing is abnormal in unaffected siblings of participants with ADHD.Method We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n = 150), their unaffected siblings (n = 92), and control participants (n = 108), all of the same age.Results Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex and ventral striatum. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and ventral striatum during receipt.Conclusion ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD, and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters are needed to replicate our findings.

AI snapshot

Written from the paper’s full text.

TL;DR

In adolescents and young adults with ADHD, reward anticipation and receipt elicited increased neural responses in frontostriatal and related regions compared with controls. Unaffected siblings showed similar increases in several of these regions, suggesting familial influences on altered reward processing.

Key findings

  • Participants with ADHD (n=150) showed increased responses versus controls (n=108) during reward anticipation in the anterior cingulate, anterior frontal cortex, and cerebellum, and during reward receipt in the orbitofrontal cortex, occipital cortex, and ventral striatum.
  • Unaffected siblings (n=92) also showed increased responses in these regions, except for the cerebellum during anticipation and the orbitofrontal cortex during receipt.
  • Behaviorally, rewarded trials produced faster reaction times than neutral trials (295 ms vs. 323 ms; t[335]=−19.4; p<0.001), and CV showed a main effect of cue (0.186 vs. 0.235; t[349]=5.9; p<0.001) plus a group effect (F[2,275]=3.1; p<0.04), with larger reward-related reductions in variability in ADHD versus controls (t[236]=−2.4; p<0.02).
  • Ventral striatum ROI analyses showed increased BOLD response for rewarded versus neutral trials during anticipation (t[257]=5.0; p<0.001) and receipt (t[257]=5.8; p<0.001); for receipt, ADHD showed increased response versus controls (F[2,334]=3.2; p<0.04; t[334]=2.44; p<0.04), while siblings did not differ from either group.

Methods

  • Event-related fMRI with an adapted monetary incentive delay task in the NeuroIMAGE cohort; analyzed 350 participants: 150 with ADHD, 92 unaffected siblings, and 108 controls, all of the same age.
  • ADHD diagnosis was based on DSM-5 criteria using K-SADS and ADHD questionnaires; all participants discontinued ADHD medication for 48 hours before testing.
  • Main analyses used first-level GLMs and second-level random-effects FSL FLAME whole-brain comparisons (cluster-level GRF correction, p<0.025), followed by ANOVAs with family as a random effect for familiality analyses and anatomical ventral striatum/nucleus accumbens ROI analyses.

Limitations

  • The paper states the MID task was modified: only one reward level with relatively low reward magnitude (20 cents vs. $5) and lowered hit probability (33% vs. 66%), which may affect comparability with standard MID studies.
  • The task was not optimized for reward receipt; receipt-related trials were relatively few and unequally distributed (twice as many misses as hits), possibly yielding suboptimal estimation of receipt effects.
  • The authors note they cannot exclude that hyperactivation during anticipation and receipt reflects non-reward-specific processing of salient events; they also call for future replication with standard MID parameters. Evident from the text: gender was unequally distributed, with a higher percentage of men with ADHD than in the other groups (Chi2[2]=23.3; p<0.01), and the study is cross-sectional, so age-related developmental interpretations could not be tested longitudinally.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jaac.2015.02.012

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

24 of 41 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Evidence from imaging studies on reward processing in healthy participants suggests that reward processing in the striatum is dependent on both reward magnitude and reward probability.

    “Evidence from imaging studies on reward processing in healthy participants suggests that reward processing in the striatum is dependent on both of these parameters 44.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [44] Yacubian, 2006, Dissociable systems for gain- and loss-related value predictions and errors of prediction in the human brain, J Neurosci source
  • Premisecitation

    Siblings of participants with ADHD have a two- to eight-fold elevated risk of ADHD relative to control participants.

    “Siblings of participants with ADHD, who share on average 50% of their genetic information, have a two- to eight-fold elevated risk of ADHD relative to control participants22.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [22] Rommelse, 2011, A review on cognitive and brain endophenotypes that may be common in autism spectrum disorder and attention-deficit/hyperactivity disorder and facilitate the search for pleiotropic genes, Neurosci Biobehav Rev source

      Section 1 (“ASD and ADHD”) reports that ADHD is strongly heritable, and sections 5.7–5.8 discuss traits in siblings of people with ADHD. None of these passages gives siblings’ risk of an ADHD diagnosis relative to controls. Searches for the two- to eight-fold figure and sibling ADHD risk found no passage establishing that comparison. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • Rests on an assumption: Siblings of participants with ADHD share on average 50% of their genetic information.
  • Premisecitation

    Studies have mainly shown hypersensitivity of the reward system in adolescents.

    “Evidence supporting this account comes from studies showing developmental changes in neural firing of the reward system. These studies have mainly shown hypersensitivity of the reward system in adolescents. 40”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [40] Galvan, 2010, Adolescent development of the reward system, Front Hum Neurosci source
  • Premisecitation

    In the healthy population, impulsivity is associated with increases in sensitivity to reward.

    “Moreover, impulsivity is in the healthy population associated with increases in sensitivity to reward 15.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Plichta, 2014, Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analytic review of the fMRI literature, Neurosci Biobehav Rev source
  • Findingown data

    During reward receipt, participants with ADHD showed increased responses relative to control participants in the occipital cortex.

    “During receipt, the same comparison revealed a significant main effect of ADHD in the occipital cortex and two regions in the OFC, one of them extending into the amygdala.”
    Quote in the paperSubstantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 41

  • May combine two claims.

    Premisecitation

    Two studies have reported oversensitivity to reward and abnormal preference for immediate reward in unaffected siblings of participants with ADHD.

    “These studies have reported oversensitivity to reward and abnormal preference for immediate reward in unaffected siblings 6,9.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [6] Uebel, 2010, Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD, Journal of Child Psychology and Psychiatry source

      The Discussion (‘Incentives and performance’; page unavailable) reports that unaffected siblings showed an intermediate response to incentives and suggests that reward sensitivity may be an ADHD endophenotype. The paper does not report a preference for immediate reward in those siblings, and its cautious account of reward sensitivity does not establish oversensitivity as a fact. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [9] Marco, 2009, Delay and reward choice in ADHD: An experimental test of the role of delay aversion, Neuropsychology source

      The Analytical Strategy section says the sibling analysis excluded siblings with ADHD, and the sibling-performance results report that unaffected siblings of ADHD probands who preferred smaller, sooner rewards were more likely to show that preference themselves. The paper does not separately establish oversensitivity to reward in those siblings; it describes impulsive drive for immediate rewards and delay aversion as possible processes underlying the choice pattern. Page numbers are not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Studies using a monetary incentive delay task have found alterations in ventral striatum signaling in both healthy populations and participants with ADHD.

    “studies investigating reward processing using a monetary incentive delay (MID) task have found alterations in VS signaling in both healthy populations and participants with ADHD (for review see 15).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Plichta, 2014, Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analytic review of the fMRI literature, Neurosci Biobehav Rev source

  • May combine two claims.

    Premisecitation

    Reports on behavioral measures of reward processing in ADHD are inconsistent and findings often remain unreplicated.

    “However, reports on behavioral measures of reward processing are inconsistent, and findings often remain unreplicated (e.g. 7,12,13).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [7] Groen, 2013, Risky behavior in gambling tasks in individuals with ADHD—a systematic literature review, PLoS One source

      The Results (Potential Alternate Explanatory Factors; page unavailable) report inconsistent findings on risky decision-making in ADHD gambling tasks: 10 studies had positive findings and 15 had null findings, sometimes using the same tests. This supports inconsistency in one type of behavioral reward-related measure, but the paper does not establish that behavioral measures of reward processing generally often remain unreplicated. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [12] Sjöwall, 2012, Multiple deficits in ADHD: executive dysfunction, delay aversion, reaction time variability, and emotional deficits, Journal of Child Psychology and Psychiatry source

      The Introduction and Discussion (page numbers unavailable in our copy) report inconsistent behavioral findings for delay aversion and temporal discounting in ADHD: some studies found group differences and others did not. These passages support inconsistency for those reward-related measures, but do not establish that reward-processing findings broadly often remain unreplicated. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [13] Solanto, 2007, Neurocognitive functioning in AD/HD, predominantly inattentive and combined subtypes, J Abnorm Child Psychol source

      The Discussion (page unavailable) reports that this study found no ADHD–control difference on the Delay Aversion Test despite a robust difference in an earlier study using the identical measure. That supports an example of inconsistent, unreplicated reward-related behavioral findings, but this single comparison does not establish that such findings often remain unreplicated. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Valid endophenotypes can be found at a higher rate in unaffected family members than in the general population.

    “it has been proposed that valid endophenotypes can be found at a higher rate in unaffected family members than in the general population 23,24.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [23] Dreher, 2009, Variation in dopamine genes influences responsivity of the human reward system, Proceedings of the National Academy of Sciences source

      The Results and Conclusion (pages not provided) discuss dopamine genotypes and reward-related brain activity, not the prevalence of endophenotypes among unaffected family members. Searches for endophenotypes and unaffected relatives found no passage comparing them with the general population. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [24] Brookes, 2006, The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes, Mol Psychiatry source

      The Introduction reports higher ADHD risk among siblings than in the general population, but it does not say that unaffected family members have endophenotypes at a higher rate. Searches for “endophenotype” and unaffected relatives found no passage in our copy making that comparison; the term appears only in a reference title. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Genetic effects on reward processing in control participants have been described.

    “Moreover, genetic effects on reward processing in control participants have been described 25.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [25] Rommelse, 2008, Neuropsychological measures probably facilitate heritability research of ADHD, Archives of Clinical Neuropsychology source

      The Results (§3.1–3.2; page unavailable) report familial influences on cognitive and motor neuropsychological measures, and the Participants section (§2.1; page unavailable) includes control families. No passage found when searching for reward processing, reward, or reinforcement describes genetic effects on reward processing in control participants. (LLM, conf=0.75)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Adolescence is characterized by behavioral changes such as increased risk-taking and behavioral impulsivity, putatively caused by an imbalance of basal ganglia and prefrontal cortex maturation.

    “Adolescence is thought to be characterized by behavioral changes such as increased risk-taking and behavioral impulsivity 41,42 putatively caused by an imbalance of basal ganglia and prefrontal cortex maturation.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [41] Casey, 2010, Neurobiology of the adolescent brain and behavior: implications for substance use disorders, J Am Acad Child Adolesc Psychiatry source
    • cites [42] Arnett, 1999, Adolescent storm and stress, reconsidered, American Psychological Association source

  • Classified as probably not a substantial claim.

    Premisecitation

    An increased response in the same ventral striatum area during reward receipt but not during reward anticipation has been reported.

    “However, an increased response in the same VS area during reward receipt but not during reward anticipation has been reported, as well.17”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] Paloyelis, 2012, Striatal Sensitivity During Reward Processing in Attention-Deficit/Hyperactivity Disorder, J Am Acad Child Adolesc Psychiatry source

  • Classified as probably not a substantial claim.

    Premisecitation

    The monetary incentive delay task has been repeatedly shown to elicit a neural response in the ventral striatum to both reward anticipation and receipt.

    “The MID task has been repeatedly shown to elicit a neural response in the VS to both reward anticipation and receipt (for review see 15,18-20).”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [15] Plichta, 2014, Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analytic review of the fMRI literature, Neurosci Biobehav Rev source

      Section 2 describes the MID task as measuring reward anticipation and feedback, including the monetary outcome, and reports ventral-striatal responses during anticipation. It does not establish that the task repeatedly elicits a ventral-striatal response at reward receipt; its feedback finding concerns the absence of a difference between ADHD and control groups. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [18] Sescousse, 2013, Processing of primary and secondary rewards: A quantitative meta-analysis and review of human functional neuroimaging studies, Neurosci Biobehav Rev source
    • cites [19] Faraone, 2010, Molecular Genetics of Attention Deficit Hyperactivity Disorder, Psychiatric Clinics of North America source

      The DRD4 and dopamine-transporter sections discuss ADHD genetics, not responses to the monetary incentive delay task. Searches for the task and for ventral-striatal responses during reward anticipation and receipt found no passage addressing the claim; page numbers were unavailable. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [20] Faraone, 2001, The nature and heritability of attention-deficit/hyperactivity disorder, Child Adolesc Psychiatr Clin N Am source

  • May combine two claims.

    Interpretationcitation

    The study's data are in contrast with reports of decreased responsiveness of the VS in anticipation of reward in adults with ADHD and with one study with adolescents with ADHD.

    “However, they are in contrast with reports of decreased responsiveness of the VS in anticipation of reward in adults with ADHD,15 as well as with one study with adolescents with ADHD.16”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [15] Plichta, 2014, Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analytic review of the fMRI literature, Neurosci Biobehav Rev source
    • cites [16] Scheres, 2007, Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder, Biological Psychiatry source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Participants with ADHD might experience the inability to gain reward as overly aversive, which may result in a stronger signal of the brain to avoid such a situation in future.

    “A third explanation would be that participants with ADHD experience the inability to gain reward as overly aversive, which may result in a stronger signal of the brain to avoid such a situation in future 39.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [39] Lemiere, 2012, Brain activation to cues predicting inescapable delay in adolescent Attention Deficit/Hyperactivity Disorder: an fMRI pilot study, Brain Res source

      The Introduction (page unavailable) proposes that delay itself is aversive for children with ADHD and predicts heightened brain activation when delay is inescapable. The Discussion (page unavailable) reports greater activation to cues of inescapable delay, but the study did not test inability to gain a reward or whether that signal helps participants avoid such a situation in future. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Signals in the striatum are most robust when high rewards are at stake, while responses to lower rewards are present yet less reproducible.

    “Indeed, signals in the striatum are most robust when high rewards are at stake, while responses to lower rewards are present yet less reproducible 45.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [45] Wu, 2014, Affective traits link to reliable neural markers of incentive anticipation, Neuroimage source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The reported hyper-activation during reward anticipation and receipt might reflect non-reward specific effects of ADHD on the processing of salient events.

    “Specifically, we cannot exclude the possibility that the reported hyper-activation during reward anticipation and receipt reflects non-reward specific effects of ADHD on the processing of salient events 49.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [49] Zink, 2003, Human striatal response to salient nonrewarding stimuli, J Neurosci source

  • May combine two claims.

    Study design and conductown data

    The receipt-related effects reported are robust and reliable based on the sample size and the clear main task effect of receipt.

    “Nevertheless, we are confident that the receipt-related effects reported here are robust and reliable based on the size of the sample we used as well as the clear main task effect of receipt (irrespective of group) that is in line with previous reports 47.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [47] Liu, 2011, Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies, Neurosci Biobehav Rev source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Striatal structures are known to show biphasic responses, making them capable of responding to positive (reward) as well as negative (punishment) stimulation.

    “Indeed, striatal structures are known to show biphasic responses, making them capable of responding to positive (reward) as well as negative (punishment) stimulation.47”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [47] Liu, 2011, Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies, Neurosci Biobehav Rev source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Experimental findings demonstrate increased responses in reward processing brain regions to delayed rewards.

    “Moreover, such an account would be in line with experimental findings demonstrating increased responses in reward processing brain regions to delayed rewards 39.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [39] Lemiere, 2012, Brain activation to cues predicting inescapable delay in adolescent Attention Deficit/Hyperactivity Disorder: an fMRI pilot study, Brain Res source

      The Abstract and Discussion report increased activation in the ventral striatum and orbito-frontal cortex, regions involved in reward processing, in adolescents with ADHD. But the measured responses were to cues predicting inescapable delay, not to delayed rewards themselves; the finding is also specific to an ADHD-related comparison in a pilot study. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    None of the brain regions showed a significant effect of age or interaction between age and diagnosis.

    “None of the brain regions (i.e. clusters from the ADHD-control comparison and NAcc during anticipation and receipt) showed a significant effect of age or interaction between age and diagnosis”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the cerebellum during reward anticipation, participants with ADHD had increased responses relative to unaffected siblings and control participants, while unaffected siblings and control participants did not differ.

    “In two other regions (anticipation: cerebellum; receipt: OFC), participants with ADHD had increased brain responses relative to their unaffected siblings and control participants; the responses of unaffected siblings and control participants did not differ from each other.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The study did not find support for the age-related interpretation because effects of age or an interaction of age by diagnosis were non-significant.

    “However, we did not find support for this interpretation in our study since effects of age or an interaction of age by diagnosis were non-significant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In one orbitofrontal cortex region during reward receipt, participants with ADHD had increased responses relative to unaffected siblings and control participants, while unaffected siblings and control participants did not differ.

    “In two other regions (anticipation: cerebellum; receipt: OFC), participants with ADHD had increased brain responses relative to their unaffected siblings and control participants; the responses of unaffected siblings and control participants did not differ from each other.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Unaffected siblings of participants with ADHD showed the same altered response to reward anticipation (frontal pole; ACC) and receipt (occipital lobe; OFC) as their affected siblings, whereas no changes were observed in the cerebellum (anticipation) and the OFC (receipt).

    “Unaffected siblings of the participants with ADHD showed the same altered response to reward anticipation (frontal pole; ACC) and receipt (occipital lobe; OFC) as their affected siblings whereas no changes could be observed in the cerebellum (anticipation) and the OFC (receipt).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Written informed consent was obtained from all participants or their legal guardians.

    “Written informed consent was obtained from all participants or their legal guardians (for participants <12 years).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All participants had discontinued use of medication for 48 hours prior to testing.

    “All participants had discontinued use of medication for 48 hours prior to testing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    Both unaffected siblings and control participants were free of ADHD.

    “Both unaffected siblings and control participants were free of ADHD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    ADHD is associated with abnormal reward processing.

    “more recent cognitive models of ADHD have indicated deficits in reward processing.4”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Luman, 2010, Identifying the neurobiology of altered reinforcement sensitivity in ADHD: a review and research agenda, Neurosci Biobehav Rev source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Gender was unequally distributed with a higher percentage of men with ADHD compared to the other groups.

    “gender was unequally distributed with a higher percentage of men with ADHD compared to the other groups (Chi2[2]=23.3; p<0.01).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Ventral striatum responses during reward anticipation for adolescents with ADHD were lower than for control participants, but no differences were observed during reward receipt.

    “VS responses during reward anticipation for adolescents with ADHD were observed to be lower than for control participants, but no differences were observed during reward receipt.16”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Scheres, 2007, Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder, Biological Psychiatry source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Participants with ADHD might overestimate the expected value of reward outcome.

    “Consequently, it might be that participants with ADHD overestimate the expected value of reward outcome.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Adult ADHD might be different from adolescent ADHD in terms of neural underpinnings.

    “Another possibility is that adult ADHD is different from adolescent ADHD in terms of neural underpinnings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Participants with ADHD might recruit more resources to monitor actions or prepare a response.

    “Additionally, they might recruit more resources to monitor actions or prepare a response.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Head movements exceeding 0.5 mm were considered movement artifacts and a motion regressor was inserted to control for possible movement artifacts.

    “The motion regressor was inserted to control for possible movement artifacts 33. Head movements from one image to the next exceeding 0.5 mm in either the x, y, or z direction were considered movement artifacts.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Keulers, 2012, Maturation of task-induced brain activation and long range functional connectivity in adolescence revealed by multivariate pattern classification, Neuroimage source

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Family was added as a random effect to correct for non-independence of data.

    “We therefore corrected for non-independence of data by adding family as a random effect.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The non-significant age effects may be because the participants are mainly late adolescents and young adults.

    “This may be because our participants are mainly late adolescents and young adults.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Age was not different between groups.

    “Age was not different between groups (Table 1)”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Participants with ADHD might be hypersensitive to reward because they experience receiving a reward relative to no reward as more pleasurable than control participants.

    “This would suggest that participants with ADHD might be hypersensitive to reward because they experience receiving a reward relative to no reward as more pleasurable than control participants.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The ventral striatum ROI was defined based on anatomical information to avoid non-independent voxel selection.

    “To avoid non-independent voxel selection, we defined our ROI based on anatomical information.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Only participants with at least 5 events per event type were included.

    “we only included participants with at least 5 events per event type”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Frontostriatal brain networks including the orbitofrontal cortex, medial prefrontal cortex, and ventral striatum play a crucial role in reward processing.

    “Frontostriatal brain networks, including the orbitofrontal cortex, medial prefrontal cortex, and the ventral striatum (VS) play a crucial role in reward processing (for review see 14).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Haber, 2010, The reward circuit: linking primate anatomy and human imaging, Neuropsychopharmacology source

  • May combine two claims.

    Study design and conductown data

    A modified version of the well-established monetary incentive delay paradigm was employed, which induced clear behavioral and neural activation effects as both whole-brain and ROI analyses indicated.

    “A modified version of the well-established monetary incentive delay paradigm was employed, which induced clear behavioral and neural activation effects as both whole-brain and ROI analyses indicated.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Diagnosis was based on DSM-5 criteria.

    “Diagnosis was based on DSM-5 criteria.2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] 2013

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Statistical inference used Gaussian random field theory-based significance testing with p<0.025 to correct for testing during anticipation and receipt.

    “statistical inference was done at a cluster level using Gaussian random field (GRF) theory-based significance testing (FSL 34; p<0.025 to correct for testing during anticipation and receipt)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Smith, 2004, Advances in functional and structural MR image analysis and implementation as FSL, Neuroimage source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Clinical status was reassessed by a trained professional administering the K-SADS to parents and children, complemented by ADHD questionnaires.

    “clinical status was reassessed by a trained professional administering the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS)29 to parents and children and complemented by ADHD questionnaires”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Conners, 1998, Revision and restandardization of the Conners Teacher Rating Scale (CTRS-R): factor structure, reliability, and criterion validity, J Abnorm Child Psychol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Age may have a critical influence on the functioning of the reward system.

    “Age may have a critical influence on the functioning of the reward system.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Striatal hypo-responsiveness might occur at a later age.

    “Accordingly, it might be that striatal hypo-responsiveness occurs at a later age.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Participants with ADHD might be unable to correctly establish an association between a reward-predicting cue and the receipt, leading to an increased prediction error response during reward receipt relative to non-reward.

    “Alternatively, they might be unable to correctly establish an association between a reward-predicting cue and the receipt, leading to an increased prediction error response during reward receipt relative to non-reward.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The study used strict diagnostic criteria to guarantee that unaffected siblings neither exhibited subthreshold ADHD nor differed from control participants on ADHD symptom measures.

    “Of note, we used strict diagnostic criteria to guarantee that unaffected siblings neither exhibited subthreshold ADHD nor differed from control participants on ADHD symptom measures.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All p-values were Bonferroni corrected (p<0.0083) for the number of clusters.

    “All p-values were Bonferroni corrected (p<0.0083) for the number of clusters.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Unaffected siblings show part of the disorder-specific changes in neural functioning, but these changes are present to a lesser extent.

    “Together our results suggest that unaffected siblings show part of the disorder-specific changes in neural functioning; however, these changes were present to a lesser extent.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was approved by the local ethics committee of participating centers.

    “This study was approved by the local ethics committee of participating centers.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The study examined reward processing in a large sample of carefully phenotyped participants using a family design.

    “We examined reward processing in a large sample of carefully phenotyped participants using a family design.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Due to infrequent hits, the task might have been generally experienced as too difficult, leading to frustration and surprise rather than anticipating and receiving reward.

    “Specifically, it might be that due to the infrequent hits, our task was generally experienced as too difficult, leading to frustration and surprise rather than anticipating and receiving reward.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Inconsistencies between previous studies and ours might be due to differences in reward magnitude.

    “Considering that previous studies with children and adults with ADHD have reported differences in striatal responses for a high reward condition only, it may be that inconsistencies between these studies and ours might be due to differences in reward magnitude.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The perception of a cue as rewarding or punishing depends on the context.

    “This implies that the perception of a cue as rewarding or punishing depends on the context.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The amount of trials used to estimate responses during reward receipt was relatively small and unequally distributed, with twice as many misses as hits.

    “The amount of trials used to estimate responses during reward receipt was relatively small and, with twice as many misses as hits, unequally distributed (for details see Table S1, available online).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Both reward magnitude and reward probability are coded relatively rather than absolutely.

    “Yet, both reward magnitude and reward probability are coded relatively rather than absolutely. 46”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Tobler, 2005, Adaptive coding of reward value by dopamine neurons, Science source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The task was originally designed to investigate reward anticipation and was not optimized for assessing reward receipt processing.

    “Finally, our task was originally designed to investigate reward anticipation and was not optimized for assessing reward receipt processing.”
    Quote in the paperNot a substantial claim
55 of 55

  • The paper relies on this without support.

    Siblings of participants with ADHD share on average 50% of their genetic information.

    “Siblings of participants with ADHD, who share on average 50% of their genetic information, have a two- to eight-fold elevated risk of ADHD relative to control participants22.”

  • The paper relies on this without support.

    Similarity between unaffected siblings and affected participants in neural responses to reward reflects familial factors (genes and/or shared environment).

    “Further, unaffected siblings of participants with ADHD also had increased neural responses during anticipation and during receipt, suggesting that familial factors play a role in this increased sensitivity of the reward system.”
    “The observed changes in the neural substrate underlying reward processing in symptom-free family members of participants with ADHD suggest that familial factors (i.e. genes and/or shared environment) contribute to alterations in the reward system.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Some studies have found a stronger response to reward outcome either in striatum or in OFC in ADHD patients versus controls.

    “At the same time, some studies have found a stronger response to reward outcome either in striatum (Furukawa et al., 2014; von Rhein et al., 2015) or in the OFC (Strohle et al., 2008) in ADHD patients vs. controls.”

    From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as von Rhein et al., 2015

  • Alterations in anticipatory and consummatory reward processing may underlie NSSI risk, and divergent associations between mental disorders and reward responsiveness may influence this effect.

    “Although alterations in anticipatory and consummatory reward processing may underlie risk for NSSI, divergent associations between mental disorders and reward responsiveness (e.g., MDD (91) vs. ADHD (94)) may influence this effect.”

    From Neural correlates associated with suicide and nonsuicidal self-injury in youth (2021) · cites this paper as [94]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract overstates the sibling response in the ventral striatum

    Major

    The abstract says unaffected siblings had increased responses in the regions identified during reward receipt, except the orbitofrontal cortex; this includes the ventral striatum. The Results instead report that siblings' ventral-striatum responses during receipt did not differ from control participants' responses.

1 of 1

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Related

Authors
von Rhein, D., Cools, R., Zwiers, M. P., van der Schaaf, M., Franke, B., Luman, M., Oosterlaan, J., Heslenfeld, D. J., Hoekstra, P. J., Hartman, C. A., Faraone, S. V., van Rooij, D., van Dongen, E. V., Lojowska, M., Mennes, M., & Buitelaar, J.
Affiliations
  • Radboud University Nijmegen (NL)
  • Radboud University Medical Center (NL)
  • Vrije Universiteit Amsterdam (NL)
  • University Medical Center Groningen (NL)
  • SUNY Upstate Medical University (US)
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2015-05
Volume
54
Issue
5
Pages
394-402
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2015.02.012
PMC
PMC4417499
OpenAlex
W2135391430
Cited by
108
References
51
Citations by year
2026: 7 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 11 · 2016: 17 · 2015: 6
FWCI
11.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • VU Research Portal (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
  • Syracuse University
  • State University of New York
  • Rijksuniversiteit Groningen
  • Radboud Universiteit
  • Vrije Universiteit Amsterdam
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (175.010.2007.010)
  • Accare
  • Universitair Medisch Centrum Groningen
  • Radboud Universitair Medisch Centrum
  • National Institutes of Health
  • National Institute of Mental Health (R01 MH 62873, R01MH062873)
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, reward processing, reward anticipation, unaffected siblings, family influence, frontostriatal circuits, ventral striatum, anterior cingulate cortex, orbitofrontal cortex, cerebellum, adolescents, young adults, monetary incentive delay task
MeSH terms
Behavior Rating Scale, Adolescent, Age Factors, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebellum, Female, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Reward, Task Performance and Analysis, Prefrontal Cortex, Siblings, Young Adult, Ventral Striatum

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-29.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-29.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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