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Cited by 49Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

Brain activation to cues predicting inescapable delay in adolescent Attention Deficit/Hyperactivity Disorder: An fMRI pilot study

Open access
Lemiere, Jurgen, Danckaerts, Marina, Van Hecke, Wim, Mehta, Mitul A., Peeters, Ronald, Sunaert, Stefan, Sonuga-Barke, Edmund·2012·Brain Research
DOI 10.1016/j.brainres.2012.02.027
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Abstract

Background The choice of small immediate over large delayed rewards (i.e., impulsive choice) is a signal marker of motivational style in Attention Deficit/Hyperactivity Disorder (ADHD). The delay aversion model proposes that, in part, this is a conditioned delay avoidance response. Here we test the prediction derived from this model that, in ADHD, cues predicting inescapable delay differentially activate brain regions shown previously to be responsive to motivationally salient, negatively valenced environmental events.Methods Ten adolescents with ADHD and 10 age matched controls performed a simple speeded reaction time task under two conditions. On Escape Delay trials slow responses only were punished by the imposition of post-response delay periods. On No Escape Delay trials post-response delay occurred on all trials irrespective of response speed. Using functional Magnetic Resonance Imaging (fMRI) BOLD responses were acquired to compare anticipatory brain activation following the two cue types. ROI analyses found significant ADHD-related hyperactivation following No Escape compared to Escape Delay trial cues in the insula, amygdala, ventral striatum and orbito-frontal cortex.Conclusion The results of this pilot study provide further evidence for the role of altered motivational systems in ADHD and the most direct evidence for a biological basis of delay aversion.

AI snapshot

Written from the paper’s full text.

TL;DR

In this fMRI pilot, adolescents with ADHD showed greater anticipatory brain activation than controls in the insula, amygdala, ventral striatum, and orbitofrontal cortex when cues predicted inescapable versus escapable delay. The findings are presented as preliminary support for altered motivational/aversive processing and a biological basis of delay aversion in ADHD.

Key findings

  • ROI analyses found ADHD-related hyperactivation for “No Escape Delay > Escape Delay” cues in the insula, amygdala, ventral striatum, and orbitofrontal cortex; most effects except left amygdala and right orbitofrontal cortex remained significant after small-volume FWE correction for the number of tested regions.
  • Behavioral performance did not differ between groups: average success rate was 62% for escape and 63% for no-escape trials (F(1,18)=0.216, p=0.647), with no significant RT difference between escape hits and no-escape hits (F(1,18)=1.41, p=0.251) or interaction (F(1,18)=0.852, p=0.368).
  • IQ correlated with activation in left ventral striatum (Spearman rho −0.54, p=0.021) and left OFC (Spearman rho −0.66, p=0.025); after entering IQ as a covariate, the FWE-corrected case-control difference remained significant for left OFC (FWE-corrected p=0.043).
  • The discussion states that patients showed greater activation to inescapable-delay cues in insula and amygdala, while controls generally showed the opposite pattern.

Methods

  • Ten adolescents with ADHD and 10 age-matched controls were analyzed after 2 ADHD and 2 control participants were removed for motion artifacts; ADHD participants were off medication at least 48 hours before testing, and groups differed significantly on IQ [t(18)=−4.95, p=0.0001].
  • Participants performed the Escape Delay Incentive task, based on the Monetary Incentive Delay task: on Escape Delay trials, slow responses were followed by post-response delay while fast responses escaped delay; on No Escape Delay trials, post-response delay occurred on all trials regardless of response speed. There were 30 trials of each type, presented randomly over four blocks of 15 trials.
  • fMRI BOLD data were acquired at 3 T; a hypothesis-driven ROI approach examined amygdala (50 voxels), insula (410 voxels), ventral striatum (30 voxels), and orbitofrontal cortex (160 voxels), using nonparametric SnPM analyses and a second-level random-effects comparison of “No Escape Delay > Escape Delay” between ADHD and controls.

Limitations

  • The paper states the sample size was small and the primary analyses were limited to ROIs, although ROI selection was explicitly hypothesis-driven; larger whole-brain studies are needed to replicate the findings.
  • The task lacked a control condition comparing inescapable delay with other punishments such as response cost, so the authors state they cannot rule out that heightened responses reflected a generalised impairment to cues predicting aversive outcomes, or to lack of control over outcomes generally, rather than delay-specific aversion.
  • The authors also state there was no comparison of ADHD with and without anxiety/mood disorder, no direct measure of whether ADHD patients perceived delay as more aversive, and groups were not matched on IQ, which is a significant confound given the observed activation–IQ correlations.

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

Integrity signals

Registry

Crossref · 10.1016/j.brainres.2012.02.027

Cites

98 of 98 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 16 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Most ROI effects, except those in the left amygdala and right orbitofrontal cortex, remained significant after correction for multiple comparisons across the tested regions.

    “Most of these effects (except for left amygdala and right orbito-frontal cortex) remained significant after multiple comparison correction for the number of tested regions.”
    Quote in the paperSubstantial claim
  • Findingown data

    The pilot results showed that anticipation of delay produces hyperactivation of the amygdalo-insular network.

    “Our pilot results demonstrated that the anticipation of delay results in a hyperactivation of this amygdalo-insular network.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Adolescents with ADHD experience the imposed post-response delay in the No Escape condition as aversive.
  • Findingown data

    IQ correlated substantially with activation in the left ventral striatum and left orbitofrontal cortex in the overall group.

    “Correlations between IQ and activations in the overall group were substantial for two ROIs: left ventral striatum (spearman rho -0.54, p=0.021) and left OFC (spearman rho -0.66, p=0.025).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In ROI analyses, ADHD participants showed greater increases in activation associated with inescapable delay than controls across all four regions bilaterally, including amygdala, insula, ventral striatum and orbitofrontal cortex.

    “For all regions bilaterally the pattern of results was similar with greater increases in activations associated with inescapable delay in ADHD compared to control patients.”
    • Also stated in: § 3. Discussion · hedged
      “Interestingly we also found evidence of ADHD-related alterations in activation in both the ventral striatum and the orbito-frontal cortex in the current study.”
    • Also stated in: § 3. Discussion · plain
      “In summary, we found that children with ADHD displayed a specific pattern of hyper-activation of the amygdala and the insula, brain regions shown in the past to be aversive-event sensitive, in response to cues of inescapable delay, as well as the ventral striatum and the orbito-frontal cortex.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Maladaptive inter-temporal choices, meaning preference for smaller earlier rewards over larger later rewards, are an important marker of ADHD-related impulsiveness.

    “There is a growing and fairly consistent body of evidence that maladaptive inter-temporal choices (i.e., preference for small earlier over larger later rewards), represent an important marker of ADHD-related impulsiveness (Scheres et al., 2010;Sonuga-Barke et al., 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Scheres et al., 2010 source

      Not checked in the free run.

    • cites Sonuga-Barke et al., 2008 source

      Not checked in the free run.

  • May combine two claims. 14
  • Classified as probably not a substantial claim. 16

  • May combine two claims.

    Findingown data

    The ADHD and control groups did not differ in hit rate on the task; average success rate was 62% in the escape condition and 63% in the no-escape condition.

    “The ADHD and control groups did not differ on hit rate while performing the task.For the escape condition the average success rate was 62% and for the no-escape condition 63% (F(1,18)=0.216,p=0.647).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ADHD patients showed greater activation to cues of inescapable delay than to escapable delay in the insula and amygdala, while controls generally showed the opposite pattern.

    “These predictions were confirmed by our pilot findings with patients showing greater activation to cues of inescapable delay compared to escapable delay in the insula and amygdala, while in general controls showed a pattern in the opposite direction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no significant difference between escape and no-escape hit reaction times, and no significant escape-by-group interaction.

    “No significant difference between RT escape hits versus RT no-escape hits (F(1,18)=1.41,p=0.251) or interaction effect (escape versus group) was found (F(1,18)=0.852,p=0.368).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Entering IQ as a covariate reduced the significance of FWE-corrected case-control activation differences, but the left orbitofrontal cortex difference remained significant.

    “This reduced the significance of FWE-corrected case-control differences in activations which nevertheless remained significant for the left orbito-frontal cortex (FWE-corrected p-value of 0.043).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    For ADHD patients, delay is aversive in itself and elicits a negative affective state that they work to escape or avoid.

    “It is based on the idea that, for ADHD patients delay is an aversive experience in and of itself, eliciting a negative affective state, which ADHD children work to escape or avoid (Sonuga-Barke, 1994;Sonuga-Barke et al., 2004).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Sonuga-Barke, 1994

      Not checked in the free run.

    • cites Sonuga-Barke et al., 2004 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisenone given

    The delay aversion model holds that impulsive choice in ADHD is partly a conditioned delay avoidance response.

    “The delay aversion model proposes that, in part, this is a conditioned delay avoidance response.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    The amygdala and insula are the two brain regions most consistently activated by the prospect of contingent aversive events in human imaging studies.

    “The two brain regions that have been most consistently shown to be activated by the prospect of contingent aversive events in human imaging studies are the amygdala and insula.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Nonparametric tests were applied because the study had a relatively small sample size.

    “Given the relatively small sample size in this study, nonparametric tests were applied.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    A second-level random effects analysis was applied to individual contrast images to account for subject-to-subject variability and to determine regional responses for within- and between-group comparisons.

    “The individual contrast images were used in a second-level random effects analysis to account for subject-to-subject variability and to determine stimuli-specific regional responses for within-and between-group statistical comparisons.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    In the amygdala and orbitofrontal cortex, some voxels were excluded from the ROI because susceptibility artifacts caused no signal.

    “Especially in the amygdala and the orbitofrontal cortex, some voxels were not included in the ROI, as there was no signal due to susceptibility related artifacts.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Time derivatives were included in the model to account for small variations in onset time that could affect results in event-related fMRI.

    “Time derivatives were added to account for small variances in the onset time, which might affect the results, especially in event-related fMRI experiments.”
    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

    Due to motion artifacts, 2 adolescents with ADHD and 2 control subjects were removed from further analyses, leaving 20 participants (10 ADHD and 10 controls).

    “Due to motion artifacts 2 adolescents with ADHD and 2 control subjects were removed from further analyses.Therefore, analyses were conducted with 20 participants (10 ADHD and 10 controls).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The role of the ventral striatum in anticipating aversive stimuli remains unresolved, with mixed imaging results.

    “Its role in the anticipation of aversive stimuli remains unresolved with mixed results from imaging studies (Jensen et al., 2003;Knutson & Greer, 2008).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jensen et al., 2003

      Not checked in the free run.

    • cites Knutson & Greer, 2008

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A specific role for the orbitofrontal cortex in relation to aversive events remains uncertain.

    “A specific role for OFC in relation to aversive events remains uncertain (Ursu & Carter, 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ursu & Carter, 2009

      Not checked in the free run.

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

    Premisecitation

    The ventral striatum is involved in reward processing and is activated by cues of impending rewards.

    “The ventral striatum is known to be involved in reward processing and is activated by cues of impending rewards (Knutson et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Knutson et al., 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The current results favour the idea that altered reinforcement processing in ADHD may involve a qualitative difference in what counts as reinforcement and punishment for individual children, as well as quantitative deficits in sensitivity to reinforcement.

    “From this perspective the current results favour the notion that altered reinforcement processing in ADHD in part may implicate qualitative difference in what constitutes reinforcement and punishment to individual children (i.e., the outcomes they will work to gain or to avoid) as well as quantitative deficits in sensitivity to reinforcement more generally (Sonuga-Barke, 2011).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sonuga-Barke, 2011 source

      Not checked in the free run.

    • Rests on an assumption: Adolescents with ADHD experience the imposed post-response delay in the No Escape condition as aversive.

  • May combine two claims.

    Study design and conductown data

    The groups were not matched on IQ, which represents a significant confound given the significant correlations between activations and IQ in the study.

    “Finally, our groups were not matched on IQ.This represents a significant confound given some significant correlations between significant activations and IQ in the current study.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The control children had no history of prematurity, head trauma, or any neurological or psychiatric disorder.

    “None of the control children had a history of prematurity (PML < 36 weeks), head trauma or any neurological and/or psychiatric disorder.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The ROI included only voxels that were present in every data set.

    “Only voxels that were present in all data sets were included in this ROI.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The pilot study had a small sample size, and consequently its primary analyses were limited to regions of interest.

    “First, the sample size in this pilot study was small and related to that the primary analyses were limited to ROIs.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The ROIs were defined using the BrainMap database.

    “The ROIs were defined based on the BrainMap database (Fox et al., 1994).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fox et al., 1994

      Not checked in the free run.

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

    Premisecitation

    Using time derivatives can lead to fitting implausible shapes and decreased power.

    “The use of these derivatives, however, can lead to fitting implausible shapes (Calhoun et al., 2004) and decreased power (Lindquist et al., 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Calhoun et al., 2004

      Not checked in the free run.

    • cites Lindquist et al., 2009

      Not checked in the free run.

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

    Premisecitation

    The orbitofrontal cortex is involved in coding reinforcer value and guiding decision making between different outcomes.

    “The orbito-frontal cortex is involved in coding reinforcer value and guiding decision making between different outcomes (Kennerley & Walton, 2011).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kennerley & Walton, 2011

      Not checked in the free run.

23 of 23

  • The paper relies on this without support.

    Adolescents with ADHD experience the imposed post-response delay in the No Escape condition as aversive.

    “Fourth, there was no direct measure of whether patients with ADHD perceived delay to be more aversive then controls.”

  • The paper relies on this without support.

    The Escape and No Escape conditions differ specifically in the escapability of delay, not in other aversive aspects such as lack of control over outcomes.

    “Additionally, it is possible that not having control over outcomes generally, rather than delay levels specifically, might be the aversive aspect of the no-escape trials and future studies need to control for this possibility.”
    “This means that we cannot rule out the possibility that the heightened response to cues predicting inescapable delay represented a generalised impairment towards cues predicting aversive outcomes rather than an effect specific to delay.”
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?

  • 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.”

    From Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings (2015) · cites this paper as [39]

    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

  • 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.”

    From Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings (2015) · cites this paper as [39]

    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

  • Children with ADHD report more negative affect during delays than controls.

    “These children report experiencing a more negative affect during delays than controls (Lemiere et al., 2012)”

    From Changing Delay Discounting and Impulsive Choice: Implications for Addictions, Prevention, and Human Health (2019) · cites this paper as Lemiere et al., 2012

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, 18) = 0.216reported p = .647 · recomputed p = .648

    “F(1,18)=0.216,p = .647”

  • ConsistentF(1, 18) = 1.41reported p = .251 · recomputed p = .250

    “F(1,18)=1.41,p = .251”

  • ConsistentF(1, 18) = 0.852reported p = .368 · recomputed p = .368

    “F(1,18)=0.852,p = .368”

3 of 3

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

Research works printed but not linked: 1

  1. Broyd, 2012, Electrophysiological markers of delay aversion, Neuropsychologia

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Related

Authors
Lemiere, J., Danckaerts, M., Van Hecke, W., Mehta, M. A., Peeters, R., Sunaert, S., & Sonuga-Barke, E.
Affiliations
  • KU Leuven (BE)
  • King's College London (GB)
  • Ghent University (BE)
Corresponding author
Sonuga-Barke, Edmund
ORCID
Venue
Brain Research
Publisher
Elsevier BV
Published
2012-04
Volume
1450
Pages
57-66
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/j.brainres.2012.02.027
OpenAlex
W1978912240
Semantic Scholar
97aede7f165059b1d735aa815c3a6f4e6d2900f1
Cited by
49
References
97
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 5
FWCI
4.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • FWO (Scientific Research Fund Belgium) (G.0821.11)
  • UZLeuven, Belgium
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, adolescents, delay aversion, impulsive choice, motivational salience, reward anticipation, insula, amygdala, ventral striatum, orbitofrontal cortex
MeSH terms
Adolescent, Attention, Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Cues, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Motivation, Pilot Projects, Psychomotor Performance, Reaction Time, Reward

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