Review
Neurobiological Circuits Regulating Attention, Cognitive Control, Motivation, and Emotion: Disruptions in Neurodevelopmental Psychiatric Disorders

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Objective

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders.

Method

Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies.

Results

The PFC provides “top–down” regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention.

Conclusions

Altogether, there is a good correspondence between anatomical circuitry mediating compromised functions and patterns of brain structure and function changes in children with neuropsychiatric disorders. Medications may optimize the neurochemical environment in PFC and associated circuitries, and improve structure and function.

Section snippets

Method

The ISI Web of Science and Pubmed were searched using the following search criteria from 1966 onward: “prefrontal cortex”, “basal ganglia circuits”, “cerebellar circuits”, “catecholamines”, “serotonin”, “neurotransmitters”, “ADHD/CD/OCD/MDD and MRI/fMRI”, “Methylphenidate/Atomoxetine and MRI/FMRI”, “SSRI and MRI/FMRI”.

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    • Cited by (0)

    This article was reviewed under and accepted by Deputy Editor Ellen Leibenluft, MD.

    Some of the research mentioned in this review was supported by the National Institute of Alcohol Abuse and Alcoholism grant 1RL1AA017536-01, which is part of National Center for Research Resources U54RR024350 (AFTA), and Medical Research Council grants G9900839 and G0300155, Wellcome Trust grant (053272/Z/98/Z/JRS/JP/JAT) and PPP Healthcare Foundation grants 1206/1568 (KR).

    Shire Development Inc. provided funding to Ogilvy CommonHealth Scientific Communications for editorial assistance in formatting and proofreading. The content of this manuscript, the ultimate interpretation, and the decision to submit it for publication in the Journal of the American Academy of Child and Adolescent Psychiatry were made by the authors independently.

    Disclosure: Dr. Arnsten and Yale University receive royalties from Shire Pharmaceuticals from the sales of extended release guanfacine (Intuniv™) for the treatment of attention-deficit/hyperactivity disorder. Dr. Arnsten serves as a consultant for Shire. She receives research funding from Shire and Pfizer. Dr Rubia has received funding from Eli Lilly and Co., and serves on the speakers' bureau for Eli Lilly and Co., Medice, and Shire.

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    Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.