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

https://doi.org/10.1016/j.jaac.2011.09.022Get rights and content

Objective

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.

Method

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.

Results

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.

Conclusions

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.

Section snippets

Sampling and Recruitment

The NIH MRI Study of Normal Brain Development is a multi-site project providing a normative database to characterize healthy brain maturation in relationship to behavior.31 Subjects were recruited across the United States with a population-based sampling method seeking to minimize biases of selection.32 Based on available U.S. Census 2000 data, a representative healthy sample of subjects was recruited at six pediatric study centers: Children's Hospital (Boston), Children's Hospital Medical

Demographics

Table 1 shows basic descriptive statistics of the two analyzed samples (cross-sectional and longitudinal). Males had higher mean CBCL AP scores in the cross-sectional sample (males 1.94 ± 0.21, females 1.43 ± 0.16, t = 1.97, df = 255, p = .05), and in the longitudinal data (males 1.98 ± 0.14, females 1.59 ± 0.11, t = 2.23, df = 670, p = .026). Although there were fewer AP raw scores over 8 in older children, the average AP score remained stable over time.

Cross-Sectional Analysis

There were no direct first-order or

Discussion

In this large neuroanatomical study of healthy children, a cross-sectional association between the “CBCL AP by age” interaction and cortical thickness was identified in various components of the attention network.3, 17 Associations were found in the right IFC, bilateral OFC, bilateral vmPFC, bilateral premotor/supplementary motor cortex, bilateral DLPFC, left mPFC, left dorsal anterior midcingulate cortex (dorsal ACC), left posterior cingulate cortex, left medial temporal gyrus, and a few other

References (49)

  • D. MacDonald et al.

    Automated 3D extraction of inner and outer surfaces of cerebral cortex from MRI

    NeuroImage

    (2000)
  • S. Ducharme et al.

    Right anterior cingulate cortical thickness and bilateral striatal volume correlate with Child Behavior Checklist aggressive behavior scores in healthy children

    Biol Psychiatry

    (2011)
  • M. Corbetta et al.

    Control of goal-directed and stimulus-driven attention in the brain

    Nat Rev Neurosci

    (2002)
  • J. Driver

    A selective review of selective attention research from the past century

    Br J Psychol

    (2001)
  • M. Posner et al.

    The attention system of the human brain

    Annu Rev Neurosci

    (1990)
  • P. Shaw et al.

    Intellectual ability and cortical thickness development in children and adolescents

    Nature

    (2006)
  • L. Westlye et al.

    Associations between regional thickness and attentional networks as measured by the attention network test

    Cereb Cortex

    (2011)
  • M. Cherkasova et al.

    Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry

    Can J Psychiatry

    (2009)
  • N. Makris et al.

    Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder

    Cereb Cortex

    (2007)
  • F. Castellanos et al.

    Quantative brain magnetic resonance imaging in attention-deficit hyperactivity disorder

    Arch Gen Psychiatry

    (1996)
  • F. Castellanos et al.

    Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder

    JAMA

    (2002)
  • P. Shaw et al.

    Longitudinal mapping of cortical thickness and clinical outcome in children and adolescent with attention-deficit/hyperactivity disorder

    Arch Gen Psychiatry

    (2006)
  • P. Shaw et al.

    Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation

    Proc Natl Acad Sci USA

    (2007)
  • J. Giedd et al.

    Brain development during childhood and adolescence: a longitudinal MRI study

    Nature Neurosci

    (1999)
  • Cited by (80)

    • Longitudinal Associations Between White Matter Microstructure and Psychiatric Symptoms in Youth

      2023, Journal of the American Academy of Child and Adolescent Psychiatry
    • Cortical thickness in childhood left focal epilepsy: Thinning beyond the seizure focus

      2020, Epilepsy and Behavior
      Citation Excerpt :

      Cortical thickness is a marker of neuroanatomical maturation, neural pruning and sculpting, and is sensitive to developmental change in typically developing and clinical populations [19–21]. In typical development (TD), the rate of change in cortical thickness is associated with neuropsychological performance, particularly intellectual abilities and executive functioning [22–32]. The purpose of the current study was to compare cortical thickness and surface area in children with left-hemisphere focal epilepsy (LHE) to children with TD and determine whether cortical thickness or surface area differences are associated with neuropsychological performance.

    View all citing articles on Scopus

    This article was reviewed under and accepted by Ad Hoc Editor Guido Frank, M.D.

    This project was funded in whole or in part with federal funds from the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke (contract nos. N01-HD02-3343, N01-MH9-0002, and N01-NS-9-2314, -2315, -2316, -2317, -2319, and -2320).

    The authors express special thanks to the National Institutes of Health contracting officers for their support.

    Brain Development Cooperative Group: Key personnel from the six pediatric study centers are as follows: Children's Hospital Medical Center of Cincinnati: Principal Investigator: William S. Ball, M.D.; Investigators: Anna Weber Byars, Ph.D., Mark Schapiro, M.D., Wendy Bommer, R.N., April Carr, B.S., April German, B.A., Scott Dunn, R.T.; Children's Hospital Boston: Principal Investigator: Michael J. Rivkin, M.D.; Investigators: Deborah Waber, Ph.D., Robert Mulkern, Ph.D., Sridhar Vajapeyam, Ph.D., Abigail Chiverton, B.A., Peter Davis, B.S., Julie Koo, B.S., Jacki Marmor, M.A., Christine Mrakotsky, Ph.D., M.A., Richard Robertson, M.D., Gloria McAnulty, Ph.D; University of Texas Health Science Center at Houston: Principal Investigators: Michael E. Brandt, Ph.D., Jack M. Fletcher, Ph.D., Larry A. Kramer, M.D.; Investigators: Grace Yang, M.Ed., Cara McCormack, B.S., Kathleen M. Hebert, M.A., Hilda Volero, M.D.; Washington University in St. Louis: Principal Investigators: Kelly Botteron, M.D., Robert C. McKinstry, M.D., Ph.D.; Investigators: William Warren, Tomoyuki Nishino, M.S., C. Robert Almli, Ph.D., Richard Todd, Ph.D., M.D. (deceased), John Constantino, M.D.; University of California Los Angeles: Principal Investigator: James T. McCracken, M.D.; Investigators: Jennifer Levitt, M.D., Jeffrey Alger, Ph.D., Joseph O'Neil, Ph.D., Arthur Toga, Ph.D., Robert Asarnow, Ph.D., David Fadale, B.A., Laura Heinichen, B.A., Cedric Ireland B.A.; Children's Hospital of Philadelphia: Principal Investigators: Dah-Jyuu Wang, Ph.D., and Edward Moss, Ph.D.; Investigators: Robert A. Zimmerman, M.D.; and Research Staff Brooke Bintliff, B.S., Ruth Bradford, Janice Newman, M.B.A.; Data Coordinating Center at McGill University: Principal Investigator: Alan C. Evans, Ph.D.; Investigators: Rozalia Arnaoutelis, B.S., G. Bruce Pike, Ph.D., D. Louis Collins, Ph.D., Gabriel Leonard, Ph.D., Tomas Paus, M.D., Alex Zijdenbos, Ph.D.; and Research Staff Samir Das, B.S., Vladimir Fonov, Ph.D., Luke Fu, B.S., Jonathan Harlap, Ilana Leppert, B.E., Denise Milovan, M.A., Dario Vins, B.C.; Georgetown University: Thomas Zeffiro, M.D., Ph.D., and John Van Meter, Ph.D; Harvard University/McLean Hospital: Nicholas Lange, Sc.D., and Michael P. Froimowitz, M.S., work with data coordinating center staff and all other team members on biostatistical study design and data analyses; Clinical Coordinating Center at Washington University: Principal Investigator: Kelly Botteron, M.D.; Investigators: C. Robert Almli, Ph.D., Cheryl Rainey, B.S., Stan Henderson, M.S., Tomoyuki Nishino, M.S., William Warren, Jennifer L. Edwards, M.SW., Diane Dubois R.N., Karla Smith, Tish Singer, and Aaron A. Wilber, M.S.; Diffusion Tensor Processing Center at the National Institutes of Health: Principal Investigator: Carlo Pierpaoli, M.D., Ph.D.; Investigators: Peter J. Basser, Ph.D., Lin-Ching Chang, Sc.D., Chen Guan Koay, Ph.D., and Lindsay Walker, M.S.; Principal Collaborators at the National Institutes of Health: Lisa Freund, Ph.D. (National Institute of Child Health and Human Development), Judith Rumsey, Ph.D. (National Institute of Mental Health [NIMH]), Lauren Baskir, Ph.D. (NIMH), Laurence Stanford, PhD. (National Institute on Drug Abuse [NIDA]), Karen Sirocco, Ph.D. (NIDA), Katrina Gwinn-Hardy, M.D. (National Institute of Neurological Disorders and Stroke [NINDS]) and Giovanna Spinella, M.D. (NINDS); Spectroscopy Processing Center at the University of California Los Angeles: Principal Investigator: James T. McCracken, M.D.; Investigators: Jeffry R. Alger, Ph.D., Jennifer Levitt, M.D., Joseph O'Neill, Ph.D.

    The views expressed herein do not necessarily represent the official views of the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, the U.S. Department of Health and Human Services, or any other agency of the United States Government.

    Supplemental material cited in this article is available online.

    Disclosure: Drs. Ducharme and Nguyen receive financial support from the Canadian Institutes of Health Research with a Master's Award: Frederick Banting and Charles Best Canada Graduate Scholarship. Dr. Hudziak has received funding from the National Institute of Mental Health (NIMH) and the National Institute of Diabetes and Digestive and Kidney Disease. He serves as a consultant to Erasmus University in Rotterdam and Avera Institute of Human Behavioral Genetics in Sioux Falls, South Dakota. Dr. Botteron has received funding from the National Institutes of Health, NIMH, National Institute of Child Health and Human Behavior, the National Institute of Neurological Disorders and Stroke, Communities Healing Adolescent Depression and Suicide Foundation, the McDonnell Foundation, the Simons Foundation, and Autism Speaks. Dr. Karama has received funding from the Fonds de Recherche en Santé du Québec. Dr. Evans is the founder and director of Biospective Inc. He serves as a consultant and receives stock options and licensing fees from the company. Dr. Albaugh reports no biomedical financial interests or potential conflicts of interest.

    Supplemental material cited in this article is available online.

    View full text