Meta-Analysis of Structural Imaging Findings in Attention-Deficit/Hyperactivity Disorder

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Biological Psychiatry (Impact Factor: 10.26). 06/2007; 61(12):1361-9. DOI: 10.1016/j.biopsych.2006.06.011
Source: PubMed


Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues.
We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author.
Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference=.408, p<.001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences.
This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.

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Available from: Larry J Seidman
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    • "Various structural neuroimaging studies have lent support to this theory showing volumetric differences in subcortical regions , including the caudate, putamen and globus pallidus (e.g. Aylward et al. 1996; Castellanos et al. 1996; Frodl and Skokauskas 2012; Hynd et al. 1993; Qiu et al. 2009; Valera et al. 2007) and components of the prefrontal cortex, including dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and the orbitofrontal cortex (OFC) (e.g. Bush 2011; Castellanos et al. 2002; Garrett et al. 2008; McAlonan et al. 2007; Overmeyer et al. 2001; Shaw et al. 2006; Wang et al. 2007). "
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    ABSTRACT: A growing body of work utilizing structural and functional brain imaging and neurocognitive measures of executive and attentional function indicates anomalous asymmetry in ADHD. This study examined the white-matter volume and diffusion properties of frontostriatal tracts, as a function of hemisphere, in ADHD and healthy controls. Forty-three young males (21 ADHD-Combined Type and 22 controls) aged 10-18 years underwent structural and diffusion weighted MRI. Tractography applying constrained spherical deconvolution (CSD) was used to construct frontostriatal tracts between each of caudate and putamen and each of dorsolateral prefrontal, ventrolateral prefrontal and orbitofrontal cortices (DLPFC, VLPFC and OFC) in each hemisphere, to examine both volumetric and diffusion microstructure properties. Young people with ADHD did not show the right hemisphere lateralization of volume in the Caudate-VLPFC and Caudate-DLPFC tracts that was evident in controls, however the ADHD group displayed a pronounced lateralization to the left for fractional anisotropy in the Putamen-VLPFC tracts. The degree of volume asymmetry did not correlate with symptom severity; however fractional anisotropy (FA) values that were more strongly lateralized to the left in the Putamen-VLPFC white matter were associated with greater symptom severity. ADHD was associated with anomalous hemispheric asymmetries in both tract volume and underlying white-matter microstructure in major fibre tracts of the frontostriatal system. Our observations of both weaker lateralization to the right in terms of tract volume and stronger lateralization to the left in terms of FA values for the ADHD group, suggests that previous inconsistencies in the literature may reflect the influence of such asymmetries.
    Full-text · Article · Nov 2015 · Brain Imaging and Behavior
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    • "It has been proposed that the cerebellum is involved in the time dependent perception of a delayed reward (Rubia et al. 2009). Additionally, a meta-analysis of structural MRI studies in ADHD has shown abnormal cerebellar structure with the largest differences observed in the right lobe (Valera et al. 2007). An altered perception of time in the context of a delayed reward is a potential mechanism for more impulsive discounting. "
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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.
    Full-text · Article · Oct 2015 · Acta neurobiologiae experimentalis
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    • "Moreover, there is evidence that abnormal brain lateralization might be a core component underlying dysfunctions in ADHD (Hale et al., 2008, 2009). At the structural and neuroimaging level, studies have reported atypical right hemisphere structure (Valera et al., 2007; Frodl and Skokauskas, 2012); in particular, smaller size of right frontal and prefrontal cortex were found in subjects with ADHD (Hill et al., 2003; Almeida et al., 2010). Atypical right hemisphere structure may affect attentional processing and response inhibition (Stefanatos and Wasserstein, 2001; Hart et al., 2013). "
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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.
    Full-text · Article · Sep 2015 · Frontiers in Psychology
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