Cited by 100Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

Distinguishing adolescents with ADHD from their unaffected siblings and healthy comparison subjects by neural activation patterns during response inhibition

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van Rooij, Daan, Hoekstra, Pieter J., Mennes, Maarten, von Rhein, Daniel, Thissen, Andrieke J.A.M., Heslenfeld, Dirk, Zwiers, Marcel P., Faraone, Stephen V. +5 more·2015·American Journal of Psychiatry

Abstract

OBJECTIVE: Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates. METHODS: Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124). RESULTS: Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity. CONCLUSIONS: Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.

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Crossref · 10.1176/appi.ajp.2014.13121635

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  • Functional neuroimaging surrogates of impaired inhibitory control in ADHD include decreased reactivity of several regions of the central executive network.

    “In addition, functional neuroimaging surrogates of impaired inhibitory control in ADHD include decreased reactivity of several regions of a network known as the central executive network (CEN) (e.g. bilateral dorsolateral prefrontal cortex and inferior frontal gyrus)13–15”

    From Effects of l-theanine–caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT (2020) · cites this paper as [13]

    The Results and Discussion report reduced activation in frontal regions during response inhibition in adolescents with ADHD, including the left inferior and superior frontal gyri. However, the Discussion explicitly says there was no right-sided inferior frontal hypoactivation, so this paper does not support decreased reactivity in the bilateral inferior frontal gyrus. It describes frontal-striatal and frontal-parietal networks rather than identifying the affected regions as the central executive network. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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  • A recent well-powered fMRI study using the Stop task in 185 patients with ADHD found no sex differences (56 females) on underactivation of IFC, DLPFC, ACC and temporo-parietal regions.

    “By contrast, a recent well-powered fMRI study using the Stop task in 185 patients with ADHD, found no sex differences (56 females) on the underactivation of IFC, DLPFC, ACC and temporo-parietal regions (van Rooij et al., 2015).”

    From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as van Rooij et al., 2015

    The Methods (Participants; page unavailable) report 185 participants with ADHD, and the Results (Group differences in fMRI task activation; page unavailable) report underactivation in the cited frontal, cingulate, and temporal/parietal regions. The Results (Covariate effects and sensitivity analyses; page unavailable) report no significant gender effects in the neural nodes or gender-by-diagnostic-group interactions. Our copy does not establish the claim’s specific count of 56 females. (LLM, conf=0.85)

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  • A recent individual study in 185 ADHD patients showed reduced activation in left IFC and superior frontal cortex, ACC and bilateral temporo-parietal regions, which correlated in left IFC with ADHD symptom severity and stop task performance.

    “A recent individual study in a large number of 185 ADHD patients showed reduced activation in left IFC and superior frontal cortex, ACC and bilateral temporo-parietal regions, which furthermore correlated in left IFC with ADHD symptom severity and stop task performance.”
  • The deficits were also present, albeit to a lesser degree, in unaffected siblings, suggesting that the fronto-parieto-temporal dysfunction during inhibitory control is familial.

    “The deficits were also present, albeit to a lesser degree, in unaffected siblings suggesting that the fronto-parieto-temporal dysfunction during inhibitory control is familial (van Rooij et al., 2015).”
  • A recent large-numbered study in 185 ADHD subjects found no age effects for inhibition dysfunctions.

    “The recent, large-numbered study in 185 ADHD subjects, however, found no age effects for inhibition dysfunctions (van Rooij et al., 2015).”

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Research works printed but not linked: 1

  1. [43]Simmonds DJ Pekar JJ Mostofsky SH Meta-analysis of Go / No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent Neuropsychologia 2008 46 224 32 17850833 PMC2327217

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Authors
van Rooij, D., Hoekstra, P. J., Mennes, M., von Rhein, D., Thissen, A. J. A. M., Heslenfeld, D., Zwiers, M. P., Faraone, S. V., Oosterlaan, J., Franke, B., Rommelse, N., Buitelaar, J. K., & Hartman, C. A.
Affiliations
  • From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam,...
  • University Medical Center Groningen (NL)
Venue
American Journal of Psychiatry
Published
2015-07-01
Volume
172
Issue
7
Pages
674-683
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
OpenAlex
W2117843800
Cited by
100
References
59
Citations by year
2026: 3 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 13 · 2016: 13 · 2015: 8
FWCI
11.62
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • VU Research Portal (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • 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
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, response inhibition, stop-signal task, inferior frontal cortex, frontoparietal network, executive function, family transmission, endophenotypes, siblings, adolescents, ADHD symptom severity, reaction time variability
MeSH terms
Adolescent, Attention, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Female, Follow-Up Studies, Humans, Impulsive Behavior, Inhibition, Psychological, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Psychomotor Performance, Reaction Time, Reference Values, Executive Function

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