Decreased Regional Cortical Thickness and Thinning Rate Are Associated With Inattention Symptoms in Healthy Children

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Canada.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 01/2012; 51(1):18-27.e2. DOI: 10.1016/j.jaac.2011.09.022
Source: PubMed


Children with attention-deficit/hyperactivity disorder (ADHD) have delayed cortical maturation, evidenced by regionally specific slower cortical thinning. However, the relationship between cortical maturation and attention capacities in typically developing children is unknown. This study examines cortical thickness correlates of inattention symptoms in a large sample of healthy children.
Data from 357 healthy subjects (6.0-18.4 years of age) were obtained from the NIH MRI Study of Normal Brain Development. In cross-sectional analysis (first visit, n = 257), Child Behavior Checklist Attention Problems (AP) scores were linearly regressed against cortical thickness, controlling for age, gender, total brain volume, and site. For longitudinal data (up to three visits, n = 357/672 scans), similar analyses were performed using mixed-effects linear regressions. Interactions of AP with age and gender were tested.
A cross-sectional "AP by age" interaction was found in bilateral orbito-frontal cortex, right inferior frontal cortex, bilateral ventromedial prefrontal cortex, bilateral dorsolateral prefrontal cortex, and several additional attention network regions. The interaction was due to negative associations between AP and thickness in younger subjects (6-10 years of age) that gradually disappeared over time secondary to slower cortical thinning. Similar trends were present in longitudinal analyses.
Higher AP scores were associated with thinner cortex at baseline and slower cortical thinning with aging in multiple areas involved in attention processes. Similar patterns have been identified in ADHD, suggesting a dimensional component to the link between attention and cortical maturation. The identified association between cortical maturation and attention in healthy development will help to inform studies of neuroimaging biomarkers of ADHD.

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    • "FreeSurfer morphometric procedures have been demonstrated to show good test–retest reliability across scanner manufacturers and across field strengths (Han et al. 2006). Numerous studies using FreeSurfer in typically and atypically developing school-age children are available (O'Donnell et al. 2005; Derauf et al. 2009; Ghosh et al. 2010; Ducharme et al. 2012; Juuhl-Langseth et al. 2012; Webb et al. 2012; Yang et al. 2012). "
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    ABSTRACT: Background: While many neuroimaging studies have investigated the neurobiological basis of attention deficit hyperactivity disorder (ADHD), few have studied the neurobiology of attention problems in the general population. The ability to pay attention falls along a continuum within the population, with children with ADHD at one extreme of the spectrum and, therefore, a dimensional perspective of evaluating attention problems has an added value to the existing literature. Our goal was to investigate the relationship between cortical thickness and inattention and hyperactivity symptoms in a large population of young children. Method: This study is embedded within the Generation R Study and includes 6- to 8-year-old children (n = 444) with parent-reported attention and hyperactivity measures and high-resolution structural imaging data. We investigated the relationship between cortical thickness across the entire brain and the Child Behavior Checklist Attention Deficit Hyperactivity Problems score. Results: We found that greater attention problems and hyperactivity were associated with a thinner right and left postcentral gyrus. When correcting for potential confounding factors and multiple testing, these associations remained significant. Conclusions: In a large, population-based sample we showed that young (6- to 8-year-old) children who show more attention problems and hyperactivity have a thinner cortex in the region of the right and left postcentral gyrus. The postcentral gyrus, being the primary somatosensory cortex, reaches its peak growth early in development. Therefore, the thinner cortex in this region may reflect either a deviation in cortical maturation or a failure to reach the same peak cortical thickness compared with children without attention or hyperactivity problems.
    Psychological Medicine 07/2014; 44(15):1-11. DOI:10.1017/S0033291714000877 · 5.94 Impact Factor
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    • "Prenatal tobacco and child brain morphology H El Marroun et al (Han et al, 2006; Reuter et al, 2012). Numerous studies using Freesurfer in typical and atypical developing schoolaged children are available (O'Donnell et al, 2005; Derauf et al, 2009; Ghosh et al, 2010; Ducharme et al, 2012). All Freesurfer output was visually inspected for quality control. "
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    ABSTRACT: It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onwards. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using MRI (MRI) techniques in children aged 6-8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal and precentral cortices. These children also demonstrated increased scores of affective problems. And, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of non-exposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children.Neuropsychopharmacology accepted article preview online, 7 October 2013. doi:10.1038/npp.2013.273.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2013; 39(4). DOI:10.1038/npp.2013.273 · 7.05 Impact Factor
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    • "Importantly, the demonstration of slower cortical thinning leading to a reversal in the polarity of cortical thickness associations during the development of this region demonstrates the crucial influence of age on this brain–behavior relation, and provides an important developmental context for studies of children and adolescents with mood and anxiety disorders. In conjunction with recent data on attention problems in healthy children and in ADHD (Shaw et al. 2011; Ducharme et al. 2012), this study highlights the importance of considering dynamic changes associated with age in morphometric studies of other behavior and pediatric psychiatric disorders as well. These results lay the foundation for integrative research looking at the impact of genetic, hormonal, cognitive, and other factors on associations between brain maturation and anxious/depressed symptoms. "
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    ABSTRACT: The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant "CBCL Anxious/Depressed by Age" interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (<9 years), but positively associated with thickness at older ages (15-22 years), with the shift in polarity occurring around age 12. This was secondary to a slower rate of vmPFC cortical thinning in subjects with higher scores. In young adults (18-22 years), Anxious/Depressed scores were also positively associated with precuneus/posterior cingulate cortical thickness. Potential neurobiological mechanisms underlying this maturation pattern are proposed. These results demonstrate the dynamic impact of age on relations between vmPFC and negative affect in the developing brain.
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