A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention

Department of Child Psychiatry, Institute of Psychiatry, King's College London, UK.
Cortex (Impact Factor: 5.13). 04/2011; 48(2):194-215. DOI: 10.1016/j.cortex.2011.04.007
Source: PubMed


Attention Deficit Hyperactivity Disorder (ADHD) has long been associated with abnormalities in frontal brain regions. In this paper we review the current structural and functional imaging evidence for abnormalities in children and adults with ADHD in fronto-striatal, fronto-parieto-temporal, fronto-cerebellar and fronto-limbic regions and networks. While the imaging studies in children with ADHD are more numerous and consistent, an increasing number of studies suggests that these structural and functional abnormalities in fronto-cortical and fronto-subcortical networks persist into adulthood, despite a relative symptomatic improvement in the adult form of the disorder. We furthermore present new data that support the notion of a persistence of neurofunctional deficits in adults with ADHD during attention and motivation functions. We show that a group of medication-naïve young adults with ADHD behaviours who were followed up 20 years from a childhood ADHD diagnosis show dysfunctions in lateral fronto-striato-parietal regions relative to controls during sustained attention, as well as in ventromedial orbitofrontal regions during reward, suggesting dysfunctions in cognitive-attentional as well as motivational neural networks. The lateral fronto-striatal deficit findings, furthermore, were strikingly similar to those we have previously observed in children with ADHD during the same task, reinforcing the notion of persistence of fronto-striatal dysfunctions in adult ADHD. The ventromedial orbitofrontal deficits, however, were associated with comorbid conduct disorder (CD), highlighting the potential confound of comorbid antisocial conditions on paralimbic brain deficits in ADHD. Our review supported by the new data therefore suggest that both adult and childhood ADHD are associated with brain abnormalities in fronto-cortical and fronto-subcortical systems that mediate the control of cognition and motivation. The brain deficits in ADHD therefore appear to be multi-systemic and to persist throughout the lifespan.

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Available from: Ana Cubillo, Oct 22, 2014
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    • "Weaker task activation in children with ADHD has been observed in regions related to executive function for a wide variety of experimental tasks (for review see Cubillo et al. 2012). Fewer fMRI studies of executive function have been conducted on adults with ADHD. "
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    ABSTRACT: An important characteristic of childhood attention-deficit/hyperactivity disorder (ADHD) is a bias towards small immediate versus larger delayed rewards, but it is not known if this symptom is also a feature of adult ADHD. A delay-discounting task was administered to participants with adult ADHD and a comparison group in conjunction with functional magnetic resonance imaging. Participants responded to a series of questions that required judgments between small sums of money available immediately and larger sums obtained after a temporal delay. Question parameters were adjusted by an adaptive algorithm designed to converge on each participant’s discounting indifference point, an individual set point at which there is equal valuation of both choices. In all participants, robust task activation was observed in regions previously identified in functional imaging studies of delay discounting. However, adults with ADHD showed less task activation in a number of regions including the dorsolateral prefrontal cortex, superior frontal gyrus, anterior cingulate, caudate nucleus and declive of the cerebellum. Additionally, the degree to which a participant discounted delayed rewards was inversely related to task activation in the cerebellum. The results suggest that the bias towards immediate rewards in childhood ADHD may not persist behaviorally, but instead present in adulthood as alterations in frontostriatal and frontocerebellar networks.
    Acta neurobiologiae experimentalis 10/2015; 75(3):2015. · 1.29 Impact Factor
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    • "neuroimaging level atypical lateralized brain activity has been found in many studies during rest , simple or complex task performance ( Sieg et al . , 1995 ; Chabot and Serfontein , 1996 ; Ernst et al . , 1998 ; Baving et al . , 1999 ; Tamm et al . , 2006 ; Hale et al . , 2009 ; Cortese et al . , 2012 ; Cubillo et al . , 2012 ) . This might suggest that atypical laterality is present in ADHD , but had not reached a specific degree or threshold to affect dimensionally the behavioral performance ( e . g . , reaction time ) . The threshold might be reached if ADHD scores are close to the clinical cut - off ( 65 or higher ) . Evidence in favor of this suggestion"
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    ABSTRACT: Many clinical studies reported a compromised brain lateralization in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) without being conclusive about whether the deficit existed in the left or right hemisphere. It is well-recognized that studying ADHD dimensionally is more controlled for comorbid problems and medication effects, and provides more accurate assessment of the symptoms. Therefore, the present study applied the dimensional approach to test the relationship between brain lateralization and self-reported ADHD symptoms in a population sample. Eighty-five right-handed university students filled in the Conners’ Adult ADHD Rating Scales and performed a lateralization reaction time task. The task consists of two matching conditions: one condition requires nominal identification for letters tapping left hemisphere specialization (Letter Name-Identity condition) and the other one requires physical and visuospatial identification for shapes tapping right hemisphere specialization (Shape Physical-Identity condition). The letters or shapes to be matched are presented in left or right visual field of a fixation cross. For both task conditions, brain lateralization was indexed as the difference in mean reaction time between left and right visual field. Linear regression analyses, controlled for mood symptoms reported by a depression, anxiety and stress scale, showed no relationship between the variables. These findings from a population sample of adults do not support the dimensionality of lateralized information processing deficit in ADHD symptomatology. However, group comparison analyses showed that subjects with high level of inattention symptoms close to or above the clinical cut-off had a reduced right hemisphere processing in the Shape Physical-Identity condition.
    Frontiers in Psychology 09/2015; 6(1418). DOI:10.3389/fpsyg.2015.01418 · 2.80 Impact Factor
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    • "This enables the OFC to serve as a specialized short term memory buffer, monitoring which recent actions were rewarded and predicting which future actions are most likely to be rewarded (Kahnt et al., 2010). Individuals with ADHD show relatively low sensitivity to reward related information as compared with NC, evident in lower neural activity levels in the ventral striatum (Ströhle et al., 2008), and poor OFC responsiveness to reward (Cubillo et al., 2012; Wilbertz et al., 2012). The anterior insula plays a critical role in mediating between the ventral and dorsal executive networks (primarily in the right hemisphere), and it exhibits significant functional connectivity to dorsal prefrontal brain regions involved in goal-directed behavior (Eckert et al., 2009). "
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    ABSTRACT: We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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