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Cited by 1,010Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI

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Rubia, Katya, Overmeyer, Stephan, Taylor, Eric, Brammer, Michael, Williams, Steve C.R., Simmons, Andrew, Bullmore, Edward T.·1999·American Journal of Psychiatry
DOI 10.1176/ajp.156.6.891
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Abstract

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that attention deficit hyperactivity disorder (ADHD) is associated with a dysfunction of prefrontal brain regions during motor response inhibition and motor timing. METHOD: Generic brain activation of seven adolescent boys with ADHD was compared to that of nine comparison subjects equivalent in sex, age, and IQ while they were performing a stop task, requiring inhibition of a planned motor response, and a motor timing task, requiring timing of a motor response to a sensory cue. RESULTS: The hyperactive adolescents showed lower power of response in the right mesial prefrontal cortex during both tasks and in the right inferior prefrontal cortex and left caudate during the stop task. CONCLUSIONS: ADHD is associated with subnormal activation of the prefrontal systems responsible for higher-order motor control. Functional MRI is a feasible technique for investigation of neural correlates of ADHD.

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Crossref · 10.1176/ajp.156.6.891

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  • The first fMRI studies found reduced inferior fronto-striatal activation in ADHD children relative to age-matched healthy controls during motor inhibition, which has been widely replicated.

    “The first fMRI studies conducted in very small numbers of ADHD patients found reduced inferior fronto-striatal activation in ADHD children relative to age-matched healthy controls during motor inhibition (Vaidya et al., 1998; Rubia et al., 1999), which has been widely replicated until today”

    From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Rubia et al., 1999

    The study summary reports reduced right inferior prefrontal and left caudate activation during a motor-inhibition stop task, compared with age-matched controls. But the participants were adolescents, not children; the paper also cannot establish the citing sentence’s claim that the finding was widely replicated afterward. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • RTV has been associated with poorer academic performance, motor development, and motor timing in children with ADHD.

    “RTV likewise has been associated with poorer academic performance (64), motor development (65), and motor timing (21, 66) in children with ADHD.”

    From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [21]

    The introduction (pp. 891–896) says hyperactive adolescents perform poorly on tasks requiring temporal accuracy of movement, supporting the motor-timing part of the claim. It does not link reaction-time variability (RTV) to poorer motor timing. The Delay task results report no significant group difference in timing variability. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • The PFC is underactive in many patients with ADHD.

    “this brain region is underactive in many patients with ADHD”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Rubia et al., 1999

    The Results and Discussion report lower prefrontal activation in seven adolescent boys with ADHD than in comparison subjects during motor-control tasks. This supports task-related underactivity, but the study does not establish that the PFC is generally underactive in many patients with ADHD. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The dorsolateral PFC has a smaller volume and reduced activity in patients with ADHD compared with controls.

    “Several imaging studies have shown that the dorsolateral PFC has a smaller volume and reduced activity in patients with ADHD compared with controls (Castellanos et al., 2002; Castellanos et al., 2008; Mostofsky et al., 2002; Rubia et al., 1999; Seidman et al., 2005).”

    From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Rubia et al., 1999

    The Stop task results (page unavailable) report reduced activity in right inferior and medioinferior frontal regions in seven adolescent boys with ADHD compared with nine controls; they do not identify the dorsolateral PFC as the affected region. The introduction mentions low frontal volumes from earlier structural studies, but this functional MRI study does not establish a smaller dorsolateral PFC volume. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Hypoactivation and corresponding deficient inhibition in ADHD seem responsible for inappropriate higher-order motor control mechanisms.

    “Hypoactivation and corresponding deficient inhibition in ADHD seem responsible for inappropriate higher-order motor control mechanisms (Rubia et al. 1999).”

    From The neurobiological link between OCD and ADHD (2014) · cites this paper as Rubia et al. 1999

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Cites

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Research works printed but not linked: 5

  1. [7]7. Gorenstein EE, Mammato CA, Sandy JM: Performance of in- attentive-overactive children on selected measures of prefron- tal-type function. J Clin Psychol 1989; 45:619-634
  2. [12]12. Casey BJ, Trainor R, Giedd J, Vauss Y, Vaituzis CK, Ham- burger S, Kozuch P, Rapoport JL: The role of the anterior cin- gulate in automatic and controlled processes, a developmen- tal neuroanatomical study. Dev Psychobiol 1997; 30:61-69
  3. [16]16. Zametkin AJ, Liebenauer LL, Fitzgerald GA, King AC, Minku- nas DV, Herscovitch P, Yamada EM, Cohen RM: Brain me- tabolism in teenagers with attention deficit hyperactivity disor- der. Arch Gen Psychiatry 1993; 50:333-340
  4. [29]29. Simmons A, Moore E, Williams SCR: Quality control of func- tional magnetic resonance imaging using automated data analysis and Shewhart charting. Magn Reson Med (in press)
  5. [37]37. Bullmore ET, Brammer MJ, Rabe-Hesketh S, Curtis VA, Mor- ris RG, Williams SCR, Sharma T, McGuire PK: Methods for di- agnosis and treatment of stimulus-correlated motion in ge- neric brain activation studies using fMRI. Hum Brain Mapp 1999; 16:7-22

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Related

Authors
Rubia, K., Overmeyer, S., Taylor, E., Brammer, M., Williams, S. C. R., Simmons, A., & Bullmore, E. T.
Affiliations
King's College London (GB)
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
1999-06-01
Volume
156
Issue
6
Pages
891-896
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/ajp.156.6.891
OpenAlex
W2164407653
Cited by
1,010
References
39
Citations by year
2026: 6 · 2025: 13 · 2024: 9 · 2023: 15 · 2022: 13 · 2021: 14 · 2020: 22 · 2019: 21 · 2018: 20 · 2017: 27 · 2016: 29 · 2015: 33 · 2014: 44 · 2013: 39 · 2012: 48
FWCI
22.33
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
Wellcome Trust
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, hypofrontality, prefrontal cortex, motor inhibition, motor timing, stop-signal task, caudate nucleus, inferior prefrontal cortex, adolescents
MeSH terms
Adolescent, Animals, Attention Deficit Disorder with Hyperactivity, Caudate Nucleus, Child, Frontal Lobe, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Motor Skills, Neuropsychological Tests, Prefrontal Cortex

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