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Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

ABSTRACT: Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data.To delineate the development of cortical asymmetry in children with and without ADHD.Longitudinal study.Government Clinical Research Institute.A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively.Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression.In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P < .001) was balanced against a relative left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P < .001). Age-related change in asymmetry in non-right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost.These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.

SUBMITTER: Shaw P

PROVIDER: S-EPMC2948210 | biostudies-other | 2009 Aug

REPOSITORIES: biostudies-other

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Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

Shaw Philip P Lalonde Francois F Lepage Claude C Rabin Cara C Eckstrand Kristen K Sharp Wendy W Greenstein Deanna D Evans Alan A Giedd J N JN Rapoport Judith J

Archives of general psychiatry 20090801 8

<h4>Context</h4>Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data.<h4>Objective</h4>To delineate the development of cortical asymmetry in children ...[more]

PMID: 19652128

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Project description:A growing number of studies support the theory that physical activity can effectively foster the cognitive function of children with attention-deficit hyperactivity disorder (ADHD). The present study examines the effect of acute moderate physical activity on the executive functions and attention performance of (1) typically developing children (without psychological, psychiatric or neurological diagnosis and/or associated treatment stated in their medical history); (2) treatment-naïve ADHD children; and (3) medicated children with ADHD. In the current study, a total sample of 150 (50 non-medicated, 50 medicated, and 50 typically developing) children between the ages of 6 and 12 took part in the experiment. The Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) was used to measure ADHD and the child version of the Test of Attentional Performance (KiTAP) was applied to evaluate the children's attentional and executive function performance before and after two types of intervention. In order to compare the effects of physical activity and control intervention, half of the children from each group (25 participants) took part in a 20-min long, moderately intense physical activity session on the 60-80% of their maximum heart rate, while watching a cartoon video. In the control condition, the other half of the children (25 participants) from each group watched the same cartoon video for 20 min while seated. Physical activity (compared to the just video watching control condition) had a significantly positive influence on 2 out of 15 measured parameters (median reaction time in the alertness task and error rates in the divided attention task) for the medicated group and on 2 out of the 15 measured variables (number of total errors and errors when distractor was presented, both in the distractibility task) regarding the treatment-naïve group. Future studies should focus on finding the optimal type, intensity, and duration of physical activity that could be a potential complementary intervention in treating deficits regarding ADHD in children.

Project description:ObjectiveThe neurobiological basis of inattentiveness, a core feature of attention-deficit/hyperactivity disorder (ADHD), is not yet well understood. Structural abnormalities in thalamus, especially the pulvinar nuclei, have recently been reported in ADHD. Pulvinar nuclei maintain reciprocal connections with cortical/subcortical areas, and play a central coordinating role during visual attention processing. The objective of this study was to test the hypothesis that children and young adolescents with ADHD would show atypical pulvinar-cortical functional pathways during sustained attention performance, and that these functional abnormalities would be associated with the inattentive symptoms of the disorder.MethodVisual attention task-based functional magnetic resonance imaging (fMRI) data from 22 children and young adolescents with ADHD and 22 demographically matched, normal control subjects were analyzed. Cortical activation maps and temporal correlations of activity patterns between pulvinar nuclei and the remainder of brain were constructed for each participant. Correlations between activation magnitude of pulvinar and diagnostic measures were calculated in subjects with ADHD.ResultsCompared to controls, subjects with ADHD showed significantly reduced pulvinar activations bilaterally, significantly decreased functional connectivity between bilateral pulvinar and right prefrontal regions, and significantly increased connectivity between the right pulvinar and bilateral occipital regions. In addition, the activation magnitude in the left pulvinar was negatively correlated with the DSM-IV inattentive index in ADHD group.ConclusionsAllied with previous evidence of structural abnormalities in pulvinar, the current data suggest that inappropriate development of pulvinar may lead to disrupted functional circuits for visual attention processing, and that these disruptions contribute significantly to the pathophysiological mechanisms of the inattentiveness symptoms in ADHD.

Project description:IntroductionAttention-deficit hyperactive disorder (ADHD) is the most common neurodevelopmental disorder in children. Diagnosis is currently based on behavioral criteria, but magnetic resonance imaging (MRI) of the brain is increasingly used in ADHD research. To date however, MRI studies have provided mixed results in ADHD patients, particularly with respect to the laterality of findings.MethodsWe studied 849 children and adolescents (ages 6-21 y.o.) diagnosed with ADHD (n = 341) and age-matched typically developing (TD) controls with structural brain MRI. We calculated volumetric measures from 34 cortical and 14 non-cortical brain regions per hemisphere, and detailed shape morphometry of subcortical nuclei. Diffusion tensor imaging (DTI) data were collected for a subset of 104 subjects; from these, we calculated mean diffusivity and fractional anisotropy of white matter tracts. Group comparisons were made for within-hemisphere (right/left) and between hemisphere asymmetry indices (AI) for each measure.ResultsDTI mean diffusivity AI group differences were significant in cingulum, inferior and superior longitudinal fasciculus, and cortico-spinal tracts (p < 0.001) with the effect of stimulant treatment tending to reduce these patterns of asymmetry differences. Gray matter volumes were more asymmetric in medication free ADHD individuals compared to TD in twelve cortical regions and two non-cortical volumes studied (p < 0.05). Morphometric analyses revealed that caudate, hippocampus, thalamus, and amygdala were more asymmetric (p < 0.0001) in ADHD individuals compared to TD, and that asymmetry differences were more significant than lateralized comparisons.ConclusionsBrain asymmetry measures allow each individual to serve as their own control, diminishing variability between individuals and when pooling data across sites. Asymmetry group differences were more significant than lateralized comparisons between ADHD and TD subjects across morphometric, volumetric, and DTI comparisons.

Project description:Intra-subject variability (ISV) is the most consistent behavioral deficit in Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with networks involved in sustaining task control (cingulo-opercular network: CON) and self-reflective lapses of attention (default mode network: DMN). The current study examined whether connectivity supporting attentional control is atypical in children with ADHD. Group differences in full-brain connection strength and brain-behavior associations with attentional control measures were examined for the late-developing CON and DMN in 50 children with ADHD and 50 typically-developing (TD) controls (ages 8-12 years). Children with ADHD had hyper-connectivity both within the CON and within the DMN. Full-brain behavioral associations were found for a number of between-network connections. Across both groups, more anti-correlation between DMN and occipital cortex supported better attentional control. However, in the TD group, this brain-behavior association was stronger and occurred for a more extensive set of DMN-occipital connections. Differential support for attentional control between the two groups occurred with a number of CON-DMN connections. For all CON-DMN connections identified, increased between-network anti-correlation was associated with better attentional control for the ADHD group, but worse attentional control in the TD group. A number of between-network connections with the medial frontal cortex, in particular, showed this relationship. Follow-up analyses revealed that these associations were specific to attentional control and were not due to individual differences in working memory, IQ, motor control, age, or scan motion. While CON-DMN anti-correlation is associated with improved attention in ADHD, other circuitry supports improved attention in TD children. Greater CON-DMN anti-correlation supported better attentional control in children with ADHD, but worse attentional control in TD children. On the other hand, greater DMN-occipital anti-correlation supported better attentional control in TD children.

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Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

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Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

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