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

There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test χ(1)2 = 5,609, P < 1.0 × 10−20). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.

[1]  R. Pearl Biometrics , 1914, The American Naturalist.

[2]  M. Kinsbourne MINIMAL BRAIN DYSFUNCTION AS A NEURODEVELOPMENTAL LAG , 1973, Annals of the New York Academy of Sciences.

[3]  R. Sprague,et al.  Conners' Teacher Rating Scale for use in drug studies with children — An empirical study , 1975, Journal of abnormal child psychology.

[4]  J. Tanner,et al.  The adolescent growth spurt of boys and girls of the Harpenden growth study. , 1976, Annals of human biology.

[5]  J. Winn,et al.  Brain , 1878, The Lancet.

[6]  P Jolicoeur,et al.  A lifetime asymptotic growth curve for human height. , 1988, Biometrics.

[7]  C A Mann,et al.  Quantitative analysis of EEG in boys with attention-deficit-hyperactivity disorder: controlled study with clinical implications. , 1992, Pediatric neurology.

[8]  P. Herscovitch,et al.  Brain metabolism in teenagers with attention-deficit hyperactivity disorder. , 1993, Archives of general psychiatry.

[9]  G. Engel,et al.  Neuropsychology , 1994, Schizophrenia Research.

[10]  R. Chabot,et al.  Quantitative electroencephalographic profiles of children with attention deficit disorder , 1996, Biological Psychiatry.

[11]  J. Rapoport,et al.  Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. , 1996, Archives of general psychiatry.

[12]  Streichenwein Sm,et al.  Am J Psychiatry , 1996 .

[13]  J C Rajapakse,et al.  A quantitative MRI study of the corpus callosum in children and adolescents. , 1996, Brain research. Developmental brain research.

[14]  P. Renshaw,et al.  Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls , 1997, Neurology.

[15]  P. Huttenlocher,et al.  Regional differences in synaptogenesis in human cerebral cortex , 1997, The Journal of comparative neurology.

[16]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[17]  R. Parasuraman The attentive brain , 1998 .

[18]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[19]  E. Bullmore,et al.  Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. , 1999, The American journal of psychiatry.

[20]  T. Robbins,et al.  Choosing between Small, Likely Rewards and Large, Unlikely Rewards Activates Inferior and Orbital Prefrontal Cortex , 1999, The Journal of Neuroscience.

[21]  Alan C. Evans,et al.  Automated 3-D Extraction of Inner and Outer Surfaces of Cerebral Cortex from MRI , 2000, NeuroImage.

[22]  Scott T. Grafton,et al.  Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder. , 2000, The American journal of psychiatry.

[23]  W. Reich Diagnostic interview for children and adolescents (DICA) , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[24]  R. Barry,et al.  Electroencephalogram differences in two subtypes of attention-deficit/hyperactivity disorder. , 2001, Psychophysiology.

[25]  Ruth A. Carper,et al.  Unusual brain growth patterns in early life in patients with autistic disorder , 2001, Neurology.

[26]  R. Henson,et al.  Frontal lobes and human memory: insights from functional neuroimaging. , 2001, Brain : a journal of neurology.

[27]  Alan C. Evans,et al.  Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. , 2002, JAMA.

[28]  Manjit,et al.  Neurology , 1912, NeuroImage.

[29]  Alan C. Evans,et al.  Automatic "pipeline" analysis of 3-D MRI data for clinical trials: application to multiple sclerosis , 2002, IEEE Transactions on Medical Imaging.

[30]  Stewart H Mostofsky,et al.  Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder , 2002, Biological Psychiatry.

[31]  Monique Ernst,et al.  Decision-making in a Risk-taking Task: A PET Study , 2002, Neuropsychopharmacology.

[32]  E. Ada,et al.  Technetium-99m HMPAO brain SPECT in children with attention deficit hyperactivity disorder , 2002, Annals of nuclear medicine.

[33]  B. J. Casey,et al.  Clinical, imaging, lesion, and genetic approaches toward a model of cognitive control. , 2002, Developmental psychobiology.

[34]  V. Menon,et al.  Maturation of brain function associated with response inhibition. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[35]  Jay N. Giedd,et al.  Motion Artifact in Magnetic Resonance Imaging: Implications for Automated Analysis , 2002, NeuroImage.

[36]  F. Castellanos,et al.  Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes , 2002, Nature Reviews Neuroscience.

[37]  Ruth A. Carper,et al.  Evidence of brain overgrowth in the first year of life in autism. , 2003, JAMA.

[38]  J. Larsson,et al.  “Maturational lag” hypothesis of attention deficit hyperactivity disorder: an update , 2003, Acta paediatrica.

[39]  R. Barry,et al.  A review of electrophysiology in attention-deficit/hyperactivity disorder: II. Event-related potentials , 2003, Clinical Neurophysiology.

[40]  B. Hart,et al.  Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children. , 2003, Neuropsychology.

[41]  Suzanne E. Welcome,et al.  Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder , 2003, The Lancet.

[42]  F. Tarazi,et al.  Animal models of attention-deficit hyperactivity disorder , 2003, Brain Research Reviews.

[43]  Yongsheng Zhang,et al.  Effects of Glucose on Blood Pressure and Production of Vascular Aldosterone and Corticosterone , 2004, Hormone Research in Paediatrics.

[44]  Thomas F. Nugent,et al.  Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. , 2004, Archives of general psychiatry.

[45]  Vinod Menon,et al.  Event-related FMRI evidence of frontotemporal involvement in aberrant response inhibition and task switching in attention-deficit/hyperactivity disorder. , 2004, Journal of the American Academy of Child and Adolescent Psychiatry.

[46]  Suzanne E. Welcome,et al.  Longitudinal Mapping of Cortical Thickness and Brain Growth in Normal Children , 2022 .

[47]  E. Knudsen Sensitive Periods in the Development of the Brain and Behavior , 2004, Journal of Cognitive Neuroscience.

[48]  Bartlett W. Mel,et al.  Cortical rewiring and information storage , 2004, Nature.

[49]  T. Hensch Critical period regulation. , 2004, Annual review of neuroscience.

[50]  Jan K Buitelaar,et al.  Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings. , 2004, Journal of the American Academy of Child and Adolescent Psychiatry.

[51]  M. Gill,et al.  Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD , 2005, Molecular Psychiatry.

[52]  J. Soliva,et al.  Global and regional gray matter reductions in ADHD: A voxel-based morphometric study , 2005, Neuroscience Letters.

[53]  M. Sur,et al.  Patterning and Plasticity of the Cerebral Cortex , 2005, Science.

[54]  Paul M. Thompson,et al.  Mapping cortical gray matter in the young adult brain: Effects of gender , 2005, NeuroImage.

[55]  Alan C. Evans,et al.  Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy. , 2004, Cerebral cortex.

[56]  Alan C. Evans,et al.  Cortical thickness analysis examined through power analysis and a population simulation , 2005, NeuroImage.

[57]  Alan C. Evans,et al.  Intellectual ability and cortical development in children and adolescents , 2006, Nature.

[58]  Alan C. Evans,et al.  Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. , 2006, Archives of general psychiatry.

[59]  F. Xavier Castellanos,et al.  Shifting-Related Brain Magnetic Activity in Attention-Deficit/Hyperactivity Disorder , 2006, Biological Psychiatry.

[60]  Brian Toone,et al.  Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder. , 2006, The American journal of psychiatry.

[61]  Michael P Milham,et al.  The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[62]  V. Russell Neurobiology of animal models of attention-deficit hyperactivity disorder , 2007, Journal of Neuroscience Methods.

[63]  Robert J. Barry,et al.  EEG abnormalities in adolescent males with AD/HD , 2007, Clinical Neurophysiology.

[64]  G. Bush,et al.  Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder. , 2007, Cerebral cortex.

[65]  Hyperactivity and Attention Deficit Disorder , 2007 .

[66]  Paul M. Thompson,et al.  Sexual dimorphism of brain developmental trajectories during childhood and adolescence , 2007, NeuroImage.

[67]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.