Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys.

High-functioning autistic and normal school-age boys were compared using a whole-brain morphometric profile that includes both total brain volume and volumes of all major brain regions. We performed MRI-based morphometric analysis on the brains of 17 autistic and 15 control subjects, all male with normal intelligence, aged 7-11 years. Clinical neuroradiologists judged the brains of all subjects to be clinically normal. The entire brain was segmented into cerebrum, cerebellum, brainstem and ventricles. The cerebrum was subdivided into cerebral cortex, cerebral white matter, hippocampus-amygdala, caudate nucleus, globus pallidus plus putamen, and diencephalon (thalamus plus ventral diencephalon). Volumes were derived for each region and compared between groups both before and after adjustment for variation in total brain volume. Factor analysis was then used to group brain regions based on their intercorrelations. Volumes were significantly different between groups overall; and diencephalon, cerebral white matter, cerebellum and globus pallidus-putamen were significantly larger in the autistic group. Brain volumes were not significantly different overall after adjustment for total brain size, but this analysis approached significance and effect sizes and univariate comparisons remained notable for three regions, although not all in the same direction: cerebral white matter showed a trend towards being disproportionately larger in autistic boys, while cerebral cortex and hippocampus-amygdala showed trends toward being disproportionately smaller. Factor analysis of all brain region volumes yielded three factors, with central white matter grouping alone, and with cerebral cortex and hippocampus-amygdala grouping separately from other grey matter regions. This morphometric profile of the autistic brain suggests that there is an overall increase in brain volumes compared with controls. Additionally, results suggest that there may be differential effects driving white matter to be larger and cerebral cortex and hippocampus-amygdala to be relatively smaller in the autistic than in the typically developing brain. The cause of this apparent dissociation of cerebral cortical regions from subcortical regions and of cortical white from grey matter is unknown, and merits further investigation.

[1]  T. Horbach,et al.  No Influence of Surgical Stress on Postoperative Leptin Gene Expression in Different Adipose Tissues and Soluble Leptin Receptor Plasma Levels , 2003, Hormone Research in Paediatrics.

[2]  T. Kemper,et al.  NEUROANATOMICAL OBSERVATIONS OF THE BRAIN IN AUTISM , 2003 .

[3]  R. Hu Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[4]  G. Dawson,et al.  Brain structural abnormalities in young children with autism spectrum disorder , 2002, Neurology.

[5]  N. Minshew,et al.  Effects of age on brain volume and head circumference in autism , 2002, Neurology.

[6]  T. Sigmundsson,et al.  Brain anatomy and sensorimotor gating in Asperger's syndrome. , 2002, Brain : a journal of neurology.

[7]  M. Pletnikov,et al.  Effects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage I. Brain pathology and behavioral deficits , 2002, Brain Research.

[8]  Caroline C Brown,et al.  The temporal binding deficit hypothesis of autism , 2002, Development and Psychopathology.

[9]  M. Eric Gershwin,et al.  Genetic and Immunologic Considerations in Autism , 2002, Neurobiology of Disease.

[10]  Andrew E. Switala,et al.  Minicolumnar pathology in autism , 2002, Neurology.

[11]  T. Kemper,et al.  Neuropathology of infantile autism , 1998, Molecular Psychiatry.

[12]  E. Courchesne,et al.  Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI. , 2001, Brain : a journal of neurology.

[13]  R. S. Kahn,et al.  Automatic Segmentation of the Ventricular System from MR Images of the Human Brain , 2001, NeuroImage.

[14]  N. Minshew,et al.  Brain Volume in Autism , 2001, Journal of child neurology.

[15]  Research strategies in autism: a story with two sides , 2001, Current opinion in neurology.

[16]  M S Buchsbaum,et al.  Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. , 2000, The American journal of psychiatry.

[17]  P. Calabresi,et al.  Cellular factors controlling neuronal vulnerability in the brain , 2000, Neurology.

[18]  A. Mayes,et al.  Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism , 2000, Neuroreport.

[19]  T. Sejnowski,et al.  A universal scaling law between gray matter and white matter of cerebral cortex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  P. Nunez Toward a quantitative description of large-scale neocortical dynamic function and EEG , 2000, Behavioral and Brain Sciences.

[21]  Ben A. Barres,et al.  Axonal Control of Oligodendrocyte Development , 1999, The Journal of cell biology.

[22]  N. Minshew,et al.  MRI volumes of amygdala and hippocampus in non–mentally retarded autistic adolescents and adults , 1999, Neurology.

[23]  W. Lipkin,et al.  An infection-based model of neurodevelopmental damage. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Alan C. Evans,et al.  Brain development during childhood and adolescence: a longitudinal MRI study , 1999, Nature Neuroscience.

[25]  B. Finlay,et al.  Neural development in metatherian and eutherian mammals: Variation and constraint , 1999, The Journal of comparative neurology.

[26]  Karl J. Friston,et al.  The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans. , 1999, Neuroreport.

[27]  Joseph Piven,et al.  An MRI study of the basal ganglia in autism , 1999, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[28]  E. Fombonne,et al.  Microcephaly and Macrocephaly in Autism , 1999, Journal of autism and developmental disorders.

[29]  E. Courchesne,et al.  An MRI study of autism : The cerebellum revisited , 1999, Neurology.

[30]  M. Gieron-Korthals Preschool Children With Inadequate Communication: Developmental Language Disorder, Autism, Low IQ , 1998 .

[31]  P. Levitt,et al.  Prenatal effects of drugs of abuse on brain development. , 1998, Drug and alcohol dependence.

[32]  A. Bailey,et al.  A clinicopathological study of autism. , 1998, Brain : a journal of neurology.

[33]  Otto Muzik,et al.  Impairment of dentato-thalamo-cortical pathway in autistic men: language activation data from positron emission tomography , 1998, Neuroscience Letters.

[34]  N. Laird,et al.  Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. , 1997, Statistics in medicine.

[35]  R. Rothermel,et al.  Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys , 1997, Annals of neurology.

[36]  N. Minshew,et al.  Neuropsychologic functioning in autism: Profile of a complex information processing disorder , 1997, Journal of the International Neuropsychological Society.

[37]  S. Folstein,et al.  Macrocephaly in children and adults with autism. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[38]  C. Zeanah,et al.  The clinical assessment of attachment in children under five. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[39]  A. Reiss,et al.  Brain development, gender and IQ in children. A volumetric imaging study. , 1996, Brain : a journal of neurology.

[40]  A. Bailey,et al.  Head circumference in autism and other pervasive developmental disorders. , 1996, Journal of child psychology and psychiatry, and allied disciplines.

[41]  P. Gartside,et al.  Head Circumference Measurements in Children With Autism , 1996, Journal of child neurology.

[42]  D. Kennedy,et al.  The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images. , 1996, Cerebral cortex.

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

[44]  S Arndt,et al.  Regional brain enlargement in autism: a magnetic resonance imaging study. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[45]  J. Piven,et al.  An MRI study of brain size in autism. , 1995, The American journal of psychiatry.

[46]  B. Finlay,et al.  Linked regularities in the development and evolution of mammalian brains. , 1995, Science.

[47]  D. Kennedy,et al.  The young adult human brain: an MRI-based morphometric analysis. , 1994, Cerebral cortex.

[48]  B. J. Casey,et al.  Quantitative magnetic resonance imaging of human brain development: ages 4-18. , 1996, Cerebral cortex.

[49]  U. Frith,et al.  Autism: beyond “theory of mind” , 1994, Cognition.

[50]  R. Thatcher Functional neuroimaging : technical foundations , 1994 .

[51]  E. Courchesne,et al.  Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging. , 1994, AJR. American journal of roentgenology.

[52]  H. Gurling,et al.  Failure to find linkage and increased homozygosity for the dopamine D3 receptor gene in Tourette's syndrome , 1993, The Lancet.

[53]  Anthony Bailey,et al.  Autism and megalencephaly , 1993, The Lancet.

[54]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[55]  V. Singh,et al.  Antibodies to Myelin Basic Protein in Children with Autistic Behavior , 1993, Brain, Behavior, and Immunity.

[56]  Nancy J. Minshew,et al.  Magnetic resonance imaging of the posterior fossa in autism , 1992, Biological Psychiatry.

[57]  V S Caviness,et al.  Volumetric analyses of central nervous system neoplasm based on MRI. , 1991, Pediatric neurology.

[58]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[59]  R. Darlington,et al.  Regression and Linear Models , 1990 .

[60]  D. Kennedy,et al.  Magnetic resonance imaging–based brain morphometry: Development and application to normal subjects , 1989, Annals of neurology.

[61]  B Horwitz,et al.  The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization. , 1988, Archives of neurology.

[62]  E. Courchesne,et al.  Hypoplasia of cerebellar vermal lobules VI and VII in autism. , 1988, The New England journal of medicine.

[63]  H. Kinney,et al.  Sequence of Central Nervous System Myelination in Human Infancy. II. Patterns of Myelination in Autopsied Infants , 1988, Journal of neuropathology and experimental neurology.

[64]  B. Brody,et al.  Sequence of Central Nervous System Myelination in Human Infancy. I. An Autopsy Study of Myelination , 1987, Journal of neuropathology and experimental neurology.

[65]  T. Kemper,et al.  Histoanatomic observations of the brain in early infantile autism , 1985, Neurology.

[66]  J. C. Reed Brain Pathology and Behavioral Deficits. , 1970 .

[67]  A. Minkowski,et al.  Regional Development of the Brain in Early Life , 1968 .

[68]  P. Yakovlev,et al.  The myelogenetic cycles of regional maturation of the brain , 1967 .