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Cited by 267Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder: The Influence of Arousal on Prefrontal Cortical Function

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Brennan, Avis R., Arnsten, Amy F.T.·2008·Annals of the New York Academy of Sciences
DOI 10.1196/annals.1417.007PMC PMC2863119
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Abstract

Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. Research in animals, in combination with observations of patients with cortical lesions, has shown that the PFC is critical for the regulation of behavior, attention, and affect using representational knowledge. The PFC is important for sustaining attention over a delay, inhibiting distraction, and dividing attention, while more posterior cortical areas are essential for perception and the allocation of attentional resources. The PFC in the right hemisphere is especially important for behavioral inhibition. Lesions to the PFC produce a profile of distractibility, forgetfulness, impulsivity, poor planning, and locomotor hyperactivity. The PFC is very sensitive to its neurochemical environment, and either too little (drowsiness) or too much (stress) catecholamine release in PFC weakens cognitive control of behavior and attention. Recent electrophysiological studies in animals suggest that norepinephrine enhances “signals” through postsynaptic α2A adrenoceptors in PFC, while dopamine decreases “noise” through modest levels of D1 receptor stimulation. α2A‐Adrenoceptor stimulation strengthens the functional connectivity of PFC networks, while blockade of α2 receptors in the monkey PFC recreates the symptoms of ADHD, resulting in impaired working memory, increased impulsivity, and locomotor hyperactivity. Genetic alterations in catecholamine pathways may contribute to dysregulation of PFC circuits in this disorder. Medications may have many of their therapeutic effects by optimizing stimulation of α2A adrenoceptors and D1 receptors in the PFC, thus strengthening PFC regulation of behavior and attention.

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  • Excessive DA stimulation might cause PFC dysfunction leading to impaired inhibition of undesirable behavior and a deficit in sustaining attention.

    “However, excessive DA stimulation might cause PFC dysfunction leading to impaired inhibition of undesirable behavior, and a deficit in sustaining attention, as these two behaviors are highly regulated by dopaminergic release in the PFC (Russell, 2003; Brennan and Arnsten, 2008; Arnsten, 2011).”

    From The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD (2015) · cites this paper as Brennan and Arnsten, 2008

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Authors
Brennan, A. R., & Arnsten, A. F. T.
Affiliations
Yale University (US)
Corresponding author
Arnsten, Amy F.T.
ORCID
Arnsten, Amy F.T.
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2008-05
Volume
1129
Issue
1
Pages
236-245
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1196/annals.1417.007
PMC
PMC2863119
OpenAlex
W2001683248
Cited by
267
References
26
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FWCI
3.07
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 58 d)
Locations
  • Annals of the New York Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Yale University
  • Marinus Pharmaceuticals
  • Shire
  • National Institute on Aging (R37 AG060636, R37AG006036)
  • National Institute of Mental Health (P50MH068789)
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, prefrontal cortex, alpha2A-adrenoceptor, dopamine D1 receptor, norepinephrine, catecholamines, working memory, impulsivity, distractibility, functional connectivity, striatum, cerebellum, behavioral inhibition, ADHD medication
MeSH terms
Arousal, Attention Deficit Disorder with Hyperactivity, Catecholamines, Environment, Humans, Neurons, Prefrontal Cortex

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.

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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