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Cited by 94Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder

Open access
Paloyelis, Yannis, Mehta, Mitul A., Faraone, Stephen V., Asherson, Philip, Kuntsi, Jonna·2012·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2012.05.006PMC PMC3763946
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Abstract

Objective Attention-deficit/hyperactivity disorder (ADHD) has been linked to deficits in the dopaminergic reward-processing circuitry, yet existing evidence is limited and the influence of genetic variation affecting dopamine signaling remains unknown. We investigated striatal responsivity to rewards in ADHD combined type (ADHD-CT) using functional magnetic resonance imaging (fMRI), and whether it is modulated by variation in the dopamine transporter gene (DAT1). Method We tested 29 male adolescents with ADHD-CT and 30 age-, handedness-and gender-matched healthy controls, selected for DAT110/6 haplotype dosage. Based on previous research, we focused our analysis on the ventral striatum and the caudate nucleus. Results Three main findings emerged: first, male adolescents with ADHD-CT did not differ from controls in terms of blood oxygen-level dependent (BOLD) fMRI response to reward-predicting cues (gain or loss-avoidance) in the ventral striatum. Second, male adolescents with ADHD-CT showed a relative increase, compared to controls, in the striatal BOLD response to successful outcomes. Third, DAT110/6 dosage differentially modulated neural activation to reward-predicting cues in the caudate nucleus in the ADHD-CT and control groups. Conclusions The findings challenge the idea of a deficit in anticipation-related activation in the ventral striatum in male adolescents with ADHD-CT, while suggesting that the processing of reward outcomes is dysfunctional, consistent with a recent neurobiological model of the disorder. Preliminary evidence suggests that polymorphic variations in genes affecting dopamine signaling need to be taken into consideration when investigating reward-related deficits in ADHD-CT.

AI snapshot

Written from the paper’s full text.

TL;DR

In male adolescents with ADHD combined type, fMRI during a motivated incidental learning task showed no ventral striatal cue-anticipation deficit versus controls, but increased striatal response to successful large outcomes. DAT1 10/6 haplotype dosage modulated cue-elicited caudate activation differently by diagnostic group.

Key findings

  • ADHD-CT adolescents (n=29) did not differ from controls (n=30) in ventral striatal BOLD response to reward-predicting cues for gain or loss-avoidance, irrespective of incentive magnitude or DAT1 10/6 haplotype (Fs<1.00, ns).
  • For successful outcomes, ADHD-CT showed higher activation than controls for large (£5) outcomes in the ventral striatum (F(1,54)=4.85, p=.032, η²p=.08) and caudate nucleus head (F(1,54)=6.58, p=.013, η²p=.11), but not for small (£1) outcomes (Fs<1.00, ns).
  • DAT1 10/6 dosage interacted with diagnosis during incentive anticipation (F(1,54)=4.25, p=.044, η²p=.06), with a crossover pattern: activation tended to decrease with higher DAT1 10/6 dosage in ADHD-CT but increase in controls.
  • Cue-elicited ventral striatal activation increased with incentive magnitude across groups (gain: F(1,55)=17.48, p<.001, η²p=.24; loss-avoidance: F(1,55)=8.17, p<.006, η²p=.13).

Methods

  • fMRI study of 29 Caucasian male adolescents with ADHD-CT and 30 age-, gender-, and handedness-matched controls, selected by DAT1 10/6 haplotype dosage (2 copies vs <2 copies).
  • Participants completed the Motivated Incidental Learning Task (MILT), a MID variant with incentive cues (£0, £1, £5; gain or loss-avoidance), anticipation and outcome phases, and ~80% success rate; only successful trials were analyzed.
  • ROI analyses focused on ventral striatum and caudate nucleus head/body using ANCOVA with diagnosis and DAT1 10/6 dosage as between-subjects factors, task phase, valence, and magnitude as within-subjects factors, age as covariate, and IQ-covaried repeat analyses.

Limitations

  • The paper states the sample size for genetic analyses was modest, so genetic findings should be treated as preliminary and interpreted cautiously until replicated.
  • The paper notes potential limitations from stimulant treatment history and possible comorbid oppositional-defiant disorder/conduct disorder in some patients.
  • The paper also notes that MILT differed from prior MID tasks, including higher cue-outcome certainty (~80% vs ~66%), making direct comparison across studies difficult; evident from the text, the sample was restricted to male Caucasian adolescents with ADHD-CT, limiting generalizability.

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

Integrity signals

Registry

Crossref · 10.1016/j.jaac.2012.05.006

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 78 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Male adolescents with ADHD-CT did not differ from controls in BOLD fMRI response to reward-predicting cues (gain or loss-avoidance) in the ventral striatum.

    “first, male adolescents with ADHD-CT did not differ from controls in terms of blood oxygen-level dependent (BOLD) fMRI response to reward-predicting cues (gain or loss-avoidance) in the ventral striatum.”
    • Also stated in: § Does neural activation to incentive-predicting cues and successful outcomes differ between adolescents with ADHD-CT and controls? · boosted
      “We confirmed that the ADHD-CT and control groups did not differ in terms of neural activation to incentive cues in the VS, for either incentive valence or brain hemisphere, irrespective of incentive magnitude (or DAT110/6 haplotype; Fs<1.00, ns; Figure 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    Male adolescents with ADHD-CT showed a relative increase compared to controls in the striatal BOLD response to successful outcomes.

    “Second, male adolescents with ADHD-CT showed a relative increase, compared to controls, in the striatal BOLD response to successful outcomes.”
    Quote in the paperSubstantial claim
  • Findingown data

    DAT110/6 dosage differentially modulated neural activation to reward-predicting cues in the caudate nucleus in the ADHD-CT and control groups.

    “Third, DAT110/6 dosage differentially modulated neural activation to reward-predicting cues in the caudate nucleus in the ADHD-CT and control groups.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was a significant two-way interaction between diagnosis and DAT110/6 in the incentive anticipation phase.

    “There was a significant two-way interaction between diagnosis and DAT110/6 in the incentive anticipation phase (F(1,54)=4.25, p=.044, η2p=.06; pIQ=.031)”
    Quote in the paperSubstantial claim
  • Findingown data

    The interaction of diagnosis and DAT110/6 during incentive anticipation followed a crossover pattern.

    “Figure 3 shows that the interaction of diagnosis and DAT110/6 during incentive anticipation followed a crossover pattern”
    Quote in the paperSubstantial claim
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    Neural activation in the caudate nucleus head was higher in the ADHD-CT group than controls for large (£5) outcomes, but not small (£1) outcomes.

    “Further post-hoc simple effects analyses to explore the interaction between diagnostic group and incentive magnitude showed that neural activation in the VS (F(1,54)=4.85, p=.032, η2p=.08; pIQ=.014) and the caudate nucleus head (F(1,54)=6.58, p=.013, η2p=.11; pIQ=.002) was higher in the ADHD-CT group, compared to controls, for large (£5), but not small (£1; Fs<1.00, ns) outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neural activation in the ventral striatum was higher in the ADHD-CT group than controls for large (£5) outcomes, but not small (£1) outcomes.

    “Further post-hoc simple effects analyses to explore the interaction between diagnostic group and incentive magnitude showed that neural activation in the VS (F(1,54)=4.85, p=.032, η2p=.08; pIQ=.014) and the caudate nucleus head (F(1,54)=6.58, p=.013, η2p=.11; pIQ=.002) was higher in the ADHD-CT group, compared to controls, for large (£5), but not small (£1; Fs<1.00, ns) outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ADHD-CT and control groups did not differ in neural activation to incentive cues in the ventral striatum, for either incentive valence or brain hemisphere, irrespective of incentive magnitude (or DAT110/6 haplotype).

    “We confirmed that the ADHD-CT and control groups did not differ in terms of neural activation to incentive cues in the VS, for either incentive valence or brain hemisphere, irrespective of incentive magnitude (or DAT110/6 haplotype; Fs<1.00, ns; Figure 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no significant main effects for diagnostic group, or interactions between diagnostic group, task phase and incentive valence.

    “While there were no significant main effects for diagnostic group, or interactions between diagnostic group, task phase and incentive valence, we observed significant interactions between diagnostic group, task phase and incentive magnitude in the VS and the caudate nucleus head (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The increase in VS cue-elicited activation with incentive magnitude did not differ by diagnosis or DAT1 10/6 dosage.

    “irrespective of diagnosis or DAT110/6 dosage (Fs<1.81, ns; Figure 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All groups experienced similar outcomes and contributed a similar number of trials.

    “The lack of significant group differences on indices of task performance indicated that all groups experienced similar outcomes and contributed a similar number of trials (Table 1).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Participants were pre-trained and achieved >94% correct semantic decisions.

    “Participants were pre-trained on this aspect of the task and achieved an extremely high (>94%) percentage of correct semantic decisions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DAT1 10/6 homozygosity was associated with decreased striatal responsivity to anticipated incentives in ADHD-CT and increased responsivity in controls.

    “Specifically, DAT110/6 homozygosity was associated with decreased striatal responsivity to anticipated incentives in the ADHD-CT group and increased responsivity in the control group.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Over time, midbrain dopamine neurons respond to predicting cues rather than the rewards themselves.

    “Over time, midbrain dopamine neurons respond to the predicting cues rather than the rewards themselves.10”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Schultz W Getting formal with dopamine and reward Neuron 2002 36 2 241 263 12383780 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Inferences were conducted at the cluster-level using family-wise error correction (α=0.05).

    “Inferences were conducted at the cluster-level using family-wise error correction (α=0.05); a voxel was considered for cluster-level analysis if p<.001”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Molecular genetic studies have linked risk for ADHD with polymorphic variants of dopamine genes.

    “and molecular genetic studies have indeed linked risk for ADHD with polymorphic variants of dopamine genes.30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Gizer IR Ficks C Waldman ID Candidate gene studies of ADHD: a meta-analytic review Human Genetics 2009 126 51 90 19506906 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Recent evidence suggests that joint consideration of these polymorphisms in haplotypes may provide more information than analyses of single genetic markers.

    “These polymorphisms have been separately linked with DAT density in the striatum, while recent evidence suggests that their joint consideration in haplotypes may provide more information than can be inferred from the analyses of single genetic markers.25”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Shumay E Chen J Fowler JS Volkow ND Genotype and Ancestry Modulate Brain's DAT Availability in Healthy Humans PloS one 2011 6 8 e22754 21826203 PMC3149615 source

      Not checked in the free run.

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

    Premisecitation

    In the striatum, the dopamine transporter (DAT) constitutes the main mechanism for terminating intrasynaptic dopamine activity.

    “In the striatum the dopamine transporter (DAT) constitutes the main mechanism for terminating intrasynaptic dopamine activity.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Ciliax BJ Drash GW Staley JK Immunocytochemical localization of the dopamine transporter in human brain Journal of Comparative Neurology 1999 409 1 38 56 10363710 source

      Not checked in the free run.

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

    Study design and conductown data

    Age was included as a covariate in the analyses.

    “Age was included as a covariate,42,44 and analyses were repeated covarying IQ (p-values reported separately).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Bjork JM Knutson B Fong GW Caggiano DM Bennett SM Hommer DW Incentive-elicited brain activation in adolescents: similarities and differences from young adults Journal of Neuroscience 2004 24 8 1793 1802 14985419 PMC6730402 source

      Not checked in the free run.

    • cites [44] Van Leijenhorst L Moor BG Op de Macks ZA Rombouts SARB Westenberg PM Crone EA Adolescent risky decision-making: neurocognitive development of reward and control regions Neuroimage 2010 51 345 355 20188198 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The genetic variant that predicts increased reward-related activation in the striatum also predicts increased reward-related impulsivity.

    “and suggestion that the genetic variant that predicts increased reward-related activation in the striatum also predicts increased reward-related impulsivity.22”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Hoogman M Aarts E Zwiers M Nitric oxide synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects Am J Psychiatry 2011 168 10 1099 1106 21724667 source

      Not checked in the free run.

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

    Study design and conductown data

    No co-morbid disorder was associated with either subgroup formed by stratification of the ADHD sample by DAT110/6 dosage.

    “No co-morbid disorder was associated with either subgroup formed by the stratification of the ADHD sample by DAT110/6 dosage (2 copies, <2 copies; supplement 1 and Table S1, available online).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The function of the dopaminergic mechanism and the role of polymorphic variation in dopamine genes vary with age, making extrapolation from adult studies difficult.

    “Yet the function of the dopaminergic mechanism and the role of polymorphic variation in dopamine genes vary with age,24,25 making extrapolation from adult studies difficult.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Dreher JC Meyer-Lindenberg A Kohn P Berman KF Age-related changes in midbrain dopaminergic regulation of the human reward system Proceedings of the National Academy of Sciences of the United States of America 2008 105 15106 15111 PMC2567500 18794529 source

      Not checked in the free run.

    • cites [25] Shumay E Chen J Fowler JS Volkow ND Genotype and Ancestry Modulate Brain's DAT Availability in Healthy Humans PloS one 2011 6 8 e22754 21826203 PMC3149615 source

      Not checked in the free run.

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

    Premisecitation

    The caudate nucleus is a core region of the dopamine reward-circuit, implicated in ADHD-control differences, and genetic variation in DAT1 is reported to affect its function and structure.

    “The caudate nucleus is a core region of the dopamine reward-circuit,42 implicated in ADHD-control differences,4 and genetic variation in DAT1 is reported to affect its function and structure 26,43”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [42] Bjork JM Knutson B Fong GW Caggiano DM Bennett SM Hommer DW Incentive-elicited brain activation in adolescents: similarities and differences from young adults Journal of Neuroscience 2004 24 8 1793 1802 14985419 PMC6730402 source

      Not checked in the free run.

    • cites [4] Strohle A Stoy M Wrase J Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder Neuroimage 2008 39 3 966 972 17996464 source

      Not checked in the free run.

    • cites [26] Dreher JC Kohn P Kolachana B Weinberger DR Berman KF Variation in dopamine genes influences responsivity of the human reward system Proceedings of the National Academy of Sciences of the United States of America 2009 106 2 617 622 PMC2626752 19104049 source

      Not checked in the free run.

    • cites [43] Shook D Brady C Lee PS Effect of dopamine transporter genotype on caudate volume in childhood ADHD and controls Am J Med Genet B Neuropsychiatr Genet 156B 1 28 35 20957668 PMC3010298 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous data from the same sample showed that DAT110/6 homozygosity predicted reduced reward-related impulsivity in the ADHD-CT group, but increased impulsivity in the control group.

    “Second, previous data from the same sample showed that DAT110/6 homozygosity predicted reduced reward-related impulsivity in the ADHD-CT group, but increased impulsivity in the control group.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Paloyelis Y Asherson P Mehta MA Faraone SV Kuntsi J DAT1 and COMT Effects on Delay Discounting and Trait Impulsivity in Male Adolescents with Attention Deficit/Hyperactivity Disorder and Healthy Controls Neuropsychopharmacology 2010 35 2414 2426 20736997 PMC2955909 source

      Not checked in the free run.

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

    Premisecitation

    DAT1 is mainly expressed in the striatum, with the highest density in the caudate nucleus.

    “DAT1 is mainly expressed in the striatum, with the highest density in the caudate nucleus.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Lewis DA Melchitzky DS Sesack SR Whitehead RE Auh S Sampson A Dopamine transporter immunoreactivity in monkey cerebral cortex: regional, laminar, and ultrastructural localization J Comp Neurol 2001 432 1 119 136 11241381 source

      Not checked in the free run.

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

    Study design and conductown data

    Analyses were repeated covarying IQ.

    “Age was included as a covariate,42,44 and analyses were repeated covarying IQ (p-values reported separately).”
    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 conductown data

    Data were averaged over left and right hemispheres, following a preliminary test showing no significant effect for brain hemisphere (or interaction with diagnostic group or DAT110/6).

    “Data were averaged over left and right hemispheres, following a preliminary test showing no significant effect for brain hemisphere (or interaction with diagnostic group or DAT110/6).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Stimulant treatment was discontinued at least 48 hours prior to testing.

    “Stimulant treatment (received by 72% of the ADHD-CT group) was discontinued at least 48 hours prior to testing (Table S2, available online).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Discontinuing stimulant treatment at least 48 hours before testing is sufficient to eliminate effects of stimulant treatment on neural activation.

  • May combine two claims.

    Premisecitation

    Neurochemical studies have demonstrated alterations in dopaminergic signaling in the striatum and midbrain in ADHD, and linked such alterations with inattention symptoms and motivation problems in children and adults with ADHD.

    “Neurochemical studies have demonstrated alterations in dopaminergic signaling in the striatum and the midbrain in ADHD, and linked such alterations with inattention symptoms and motivation problems in children and adults with ADHD.5,27–29”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [5] Volkow ND Wang GJ Kollins SH Evaluating dopamine reward pathway in ADHD: clinical implications JAMA 2009 302 10 1084 1091 19738093 PMC2958516 source

      Not checked in the free run.

    • cites [27] Volkow ND Wang GJ Newcorn JH Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway Molecular Psychiatry 2011 16 11 1147 54 20856250 PMC3010326 source

      Not checked in the free run.

    • cites [28] Ernst M Zametkin AJ Matochik JA Jons PH Cohen RM DOPA decarboxylase activity in attention deficit hyperactivity disorder adults. A [fluorine-18]fluorodopa positron emission tomographic study Journal of neuroscience 1998 18 15 5901 5907 9671677 PMC6793062 source

      Not checked in the free run.

    • cites [29] Ernst M Zametkin AJ Matochik JA Pascualvaca D Jons PH Cohen RM High midbrain [18F]DOPA accumulation in children with attention deficit hyperactivity disorder Am J Psychiatry 156 8 1209 1215 10450262 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Only a single study has focused on adolescents with ADHD (n=11), reporting decreased activation in the ventral striatum in the ADHD group compared to controls following cues predicting monetary gains, but not following cues predicting loss-avoidance, or in the outcome phase.

    “To date, only a single study has focused on adolescents with ADHD (n=11), reporting decreased activation in the VS in the ADHD group (compared to controls) following cues predicting monetary gains, but not following cues predicting loss-avoidance, or in the outcome phase.3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Scheres A Milham MP Knutson B Castellanos FX Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder Biological Psychiatry 2007 61 5 720 724 16950228 source

      Not checked in the free run.

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

    Study design and conductown data

    Participants achieved a high rate (>94%) of semantically correct responses.

    “Participants achieved a high rate (> 94%) of semantically correct responses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The single previous study that examined outcome-related activation in adolescents with ADHD focused solely on the VS and did not find group differences.

    “Although in agreement with previous evidence from adults with ADHD,4 the single previous study that examined outcome-related activation in adolescents with ADHD had focused solely on the VS and did not find group differences.3”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Strohle A Stoy M Wrase J Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder Neuroimage 2008 39 3 966 972 17996464 source

      Not checked in the free run.

    • cites [3] Scheres A Milham MP Knutson B Castellanos FX Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder Biological Psychiatry 2007 61 5 720 724 16950228 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    This dysfunctional transfer may result in impaired appraisal of motivational outcomes and subsequent adaptation of behavior.

    “This may result in impaired appraisal of motivational outcomes and subsequent adaptation of behavior.6”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Tripp G Wickens JR Research review: dopamine transfer deficit: a neurobiological theory of altered reinforcement mechanisms in ADHD Journal of Child Psychology and Psychiatry and Allied Disciplines 2008 49 7 691 704 18081766 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Phasic firing of midbrain dopamine neurons is expected to transfer to reward-predicting cues, and higher expected success rate would make this transfer more complete.

    “The phasic firing of midbrain dopamine neurons is expected to transfer to reward-predicting cues,6,10 and therefore the higher the expected success rate the more complete this transfer would be expected to be.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Tripp G Wickens JR Research review: dopamine transfer deficit: a neurobiological theory of altered reinforcement mechanisms in ADHD Journal of Child Psychology and Psychiatry and Allied Disciplines 2008 49 7 691 704 18081766 source

      Not checked in the free run.

    • cites [10] Schultz W Getting formal with dopamine and reward Neuron 2002 36 2 241 263 12383780 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The strength of association between cue and outcome was matched between groups, as all groups demonstrated similar success rates.

    “The strength of the association between cue and outcome was matched between groups, as all groups demonstrated similar success rates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The processing of reward outcomes is dysfunctional in ADHD-CT, which may impair learning and adaptive behavior.

    “while suggesting that the processing of reward outcomes is dysfunctional, which may impair learning and adaptive behavior.6”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Tripp G Wickens JR Research review: dopamine transfer deficit: a neurobiological theory of altered reinforcement mechanisms in ADHD Journal of Child Psychology and Psychiatry and Allied Disciplines 2008 49 7 691 704 18081766 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous MID-variants have used targets requiring an element of cognitive processing, which is controlled for by using non-incentive trials matched on semantic processing.

    “Previous MID-variants have used targets requiring an element of cognitive processing,35 which is controlled for by using non-incentive trials that are matched on semantic processing as the comparison condition.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Wittmann BC Schott BH Guderian S Frey JU Heinze HJ Düzel E Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation Neuron 2005 45 459 467 15694331 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Our findings agree with prior lack of group differences in neural activation to loss-avoidance anticipation but contradict prior reduced VS activation during gain anticipation.

    “Our findings, while in agreement with the reported lack of significant group differences in neural activation to loss-avoidance anticipation, apparently contradict the demonstration of reduced activation in the VS during gain anticipation.3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Scheres A Milham MP Knutson B Castellanos FX Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder Biological Psychiatry 2007 61 5 720 724 16950228 source

      Not checked in the free run.

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

    Premisereasoning

    MILT differed from previous applications in ADHD research in that targets comprised drawings of living and non-living objects and required a semantic judgment.

    “The second way in which MILT differed from previous applications in ADHD research (but see35 for a similar variant in cognitive neuroscience) was that, due to its nature as an incidental learning task (an aspect that is not discussed in this paper), the targets comprised drawings of living and non-living objects and required a semantic judgment (living or nonliving).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Wittmann BC Schott BH Guderian S Frey JU Heinze HJ Düzel E Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation Neuron 2005 45 459 467 15694331 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The relatively small sample size (n=11) and inclusion of both genders and mixed ADHD subtypes in the prior study make direct comparisons difficult.

    “Yet the relatively small sample size in that study (n=11)3 and the inclusion of both genders and mixed ADHD subtypes (factors that have been associated with reward-related activation and impulsivity16,45) make direct comparisons difficult.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Scheres A Milham MP Knutson B Castellanos FX Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder Biological Psychiatry 2007 61 5 720 724 16950228 source

      Not checked in the free run.

    • cites [16] Scheres A Tontsch C Thoeny AL Kaczkurkin A Temporal Reward Discounting in Attention-Deficit/Hyperactivity Disorder: The Contribution of Symptom Domains, Reward Magnitude, and Session Length Biological Psychiatry 2010 67 7 641 648 20034616 source

      Not checked in the free run.

    • cites [45] Forbes EE Ryan ND Phillips ML Healthy adolescents' neural response to reward: associations with puberty, positive affect, and depressive symptoms Journal of the American Academy of Child and Adolescent Psychiatry 2010 49 2 162 172 20215938 PMC2837556

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Successful trials in MILT are more common (~80%) compared to previous paradigms (~66%), making direct comparison across studies more difficult.

    “Yet, given that successful trials in MILT are more common (∼80%) compared to previous paradigms (∼66%), it is more difficult to directly compare findings across studies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The focus on ROIs directly relevant to reward processing reduces the possibility that findings are biased by the semantic task aspect.

    “Moreover, the focus on ROIs directly relevant to reward processing reduces the possibility that our findings are biased by this aspect of the task.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The increased certainty may have sharpened the degree to which cues elicited anticipatory activity, but would not make a qualitative difference in incentive-elicited activation.

    “Thus, the increased certainty may even have sharpened the degree to which cues elicited anticipatory activity, while we would not expect that it makes a qualitative difference with regard to incentive-elicited activation.”
    Quote in the paperNot a substantial claim
38 of 38

  • The paper relies on this without support.

    Discontinuing stimulant treatment at least 48 hours before testing is sufficient to eliminate effects of stimulant treatment on neural activation.

    “Stimulant treatment (received by 72% of the ADHD-CT group) was discontinued at least 48 hours prior to testing (Table S2, available online).”

  • The paper relies on this without support.

    Dorsal regions of the caudate also receive efferent phasic input from midbrain dopamine neurons in response to reward predicting cues.

    “Moreover, apart from the VS, dorsal regions of the caudate also receive efferent phasic input from midbrain dopamine neurons in response to reward predicting cues.”
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Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(1, 54) = 6.91reported p = .011 · recomputed p = .011

    “F(1,54)=6.91, p = .011”

  • ConsistentF(1, 54) = 12.65reported p < .001 · recomputed p < .001

    “F(1,54)=12.65, p < .001”

  • ConsistentF(1, 54) = 4.85reported p = .032 · recomputed p = .032

    “F(1,54)=4.85, p = .032”

  • ConsistentF(1, 54) = 6.58reported p = .013 · recomputed p = .013

    “F(1,54)=6.58, p = .013”

  • ConsistentF(1, 54) = 4.25reported p = .044 · recomputed p = .044

    “F(1,54)=4.25, p = .044”

  • ConsistentF(1, 54) = 1.92reported p = .17 · recomputed p = .172

    “F(1,54)=1.92, p = .17”

  • ConsistentF(1, 55) = 17.48reported p < .001 · recomputed p < .001

    “F(1,55)=17.48, p < .001”

  • ConsistentF(1, 55) = 8.17reported p < .006 · recomputed p = .006

    “F(1,55)=8.17, p < .006”

8 of 8

Self-check

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

Self-check results appear here once an independent check has confirmed them.

Cites

Flagged first, then by citations

2 of the 64 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Kuntsi, 2006, The IMAGE project: methodological issues for the molecular genetic analysis of ADHD, Behav Brain Funct, 2, 27, 10.1186/1744-9081-2-27 · DOI
  2. Conners, 1998, The revised Conners' Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity, J Abnorm Child Psychol, 26, 257, 10.1023/a:1022602400621 · DOI · Paper page
  3. Van Leijenhorst, 2010, Adolescent risky decision-making: neurocognitive development of reward and control regions, Neuroimage, 51, 345, 10.1016/j.neuroimage.2010.02.038 · DOI · Paper page
  4. Bjork, 2004, Incentive-elicited brain activation in adolescents: similarities and differences from young adults, J Neurosci, 24, 1793, 10.1523/jneurosci.4862-03.2004 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Paloyelis, Y., Mehta, M. A., Faraone, S. V., Asherson, P., & Kuntsi, J.
Affiliations
King's College London (GB)
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2012-07
Volume
51
Issue
7
Pages
722-732.e9
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2012.05.006
PMC
PMC3763946
OpenAlex
W2004311221
Semantic Scholar
0a888402411d9abf9865b33ad801936724d3422b
Cited by
94
References
64
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 13 · 2018: 5 · 2017: 2 · 2016: 13 · 2015: 10 · 2014: 15 · 2013: 8
FWCI
7.51
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
National Institute of Mental Health (R01 MH 62873, R01MH081803, R01MH062873)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
attention deficit hyperactivity disorder, combined type ADHD, reward processing, striatum, ventral striatum, caudate nucleus, dopamine transporter gene, dopamine signaling, adolescents, reward anticipation, genetic variation
MeSH terms
Adolescent, Arousal, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Brain Mapping, Caudate Nucleus, Cues, Decision Making, Dominance, Cerebral, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Motivation, Nerve Net, Oxygen, Reference Values, Reward, Feedback, Psychological, Dopamine Plasma Membrane Transport Proteins, Executive Function, Anticipation, Psychological

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 2026-10-10.

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

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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