Callosal fiber length and interhemispheric connectivity in adults with autism: Brain overgrowth and underconnectivity

Typical adults show an inverse relation between callosal fiber length and degree of interhemispheric connectivity. This has been hypothesized to be a consequence of the influence of conduction delays and cellular costs during development on axonal pruning, both of which increase with fiber length. Autism spectrum disorder (ASD) provides a test of this hypothesis: Children with ASD are known to have enlarged brains; thus, adults with ASD should show reductions in interhemispheric connectivity proportional to their degree of brain overgrowth during development. This prediction was tested by assessing the relation between both the size and structure of the corpus callosum and callosal fiber length, adjusting for intracranial volume, which is thought to reflect maximum brain size achieved during development. Using tractography to estimate the length of callosal fibers emanating from all areas of cortex, and through which region of the corpus callosum they pass, we show that adults with ASD show an inverse relation between callosal fiber length, adjusted for intracranial volume, and callosum size, and a positive relation between adjusted callosal fiber length and radial diffusivity. The results provide support for the hypothesized impact of fiber length during development. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

[1]  T. Kemper,et al.  Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism , 2011, Autism research : official journal of the International Society for Autism Research.

[2]  Alan C. Evans,et al.  Negative Associations between Corpus Callosum Midsagittal Area and IQ in a Representative Sample of Healthy Children and Adolescents , 2011, PloS one.

[3]  R. Caminiti,et al.  Evolution amplified processing with temporally dispersed slow neuronal connectivity in primates , 2009, Proceedings of the National Academy of Sciences.

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

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

[6]  Mark A. Changizi,et al.  Principles underlying mammalian neocortical scaling , 2001, Biological Cybernetics.

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

[8]  Patrice Y. Simard,et al.  Time is of the essence: a conjecture that hemispheric specialization arises from interhemispheric conduction delay. , 1994, Cerebral cortex.

[9]  Robert W Thatcher,et al.  Development of cortical connections as measured by EEG coherence and phase delays , 2008, Human brain mapping.

[10]  Marcel Adam Just,et al.  Functional connectivity in an fMRI working memory task in high-functioning autism , 2005, NeuroImage.

[11]  Alan C. Evans,et al.  Maturation of white matter in the human brain: a review of magnetic resonance studies , 2001, Brain Research Bulletin.

[12]  F. Aboitiz,et al.  Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization. , 2003, Biological research.

[13]  Abraham Z. Snyder,et al.  A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume , 2004, NeuroImage.

[14]  A. Addington,et al.  Autism-Spectrum Disorders and Childhood Onset Schizophrenia : Clinical and Biological Contributions to a Relationship Revisited , 2009 .

[15]  Andrew L. Alexander,et al.  Diffusion tensor imaging of the corpus callosum in Autism , 2007, NeuroImage.

[16]  C. J. McGrath,et al.  Effect of exchange rate return on volatility spill-over across trading regions , 2012 .

[17]  Jeffrey L Elman,et al.  Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity. , 2008, Developmental science.

[18]  A. Hardan,et al.  A Meta-Analysis of the Corpus Callosum in Autism , 2009, Biological Psychiatry.

[19]  Dmitri B. Chklovskii,et al.  Wiring Optimization in Cortical Circuits , 2002, Neuron.

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

[21]  G. Dawson.  Lateralized brain dysfunction in autism: Evidence from the Halstead-Reitan neuropsychological battery , 1983, Journal of autism and developmental disorders.

[22]  J L Ringo,et al.  Neuronal interconnection as a function of brain size. , 1991, Brain, behavior and evolution.

[23]  Jon H. Kaas,et al.  Why is Brain Size so Important:Design Problems and Solutions as Neocortex Gets Biggeror Smaller , 2000 .

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

[25]  T. Insel,et al.  Differential expansion of neural projection systems in primate brain evolution. , 1999, Neuroreport.

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

[27]  B. Hubert,et al.  Enhanced Perceptual Functioning in Autism: An Update, and Eight Principles of Autistic Perception , 2006, Journal of autism and developmental disorders.

[28]  J. Piven,et al.  Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. , 2005, Archives of general psychiatry.

[29]  Deanna Greenstein,et al.  Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[30]  T. Insel,et al.  The primate neocortex in comparative perspective using magnetic resonance imaging. , 1999, Journal of human evolution.

[31]  P. Goldman-Rakic,et al.  Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. , 1986, Science.

[32]  Alan C. Evans,et al.  Structural maturation of neural pathways in children and adolescents: in vivo study. , 1999, Science.

[33]  K. Worsley,et al.  Detecting Sparse Signals in Random Fields, With an Application to Brain Mapping , 2007 .

[34]  Nick C Fox,et al.  Normalization of cerebral volumes by use of intracranial volume: implications for longitudinal quantitative MR imaging. , 2001, AJNR. American journal of neuroradiology.

[35]  S. Miller,et al.  Constancy of central conduction delays during development in man: investigation of motor and somatosensory pathways. , 1991, The Journal of physiology.

[36]  H. Frahm,et al.  Comparison of brain structure volumes in Insectivora and Primates. I. Neocortex. , 1982, Journal fur Hirnforschung.

[37]  P Hagoort,et al.  Semantic, factual, and social language comprehension in adolescents with autism: an FMRI study. , 2010, Cerebral cortex.

[38]  J. Staiger,et al.  Using High-resolution , 2022 .

[39]  D. Delis,et al.  Hemispheric specialization of memory for visual hierarchical stimuli , 1986, Neuropsychologia.

[40]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

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

[42]  Thomas E. Nichols,et al.  Nonstationary cluster-size inference with random field and permutation methods , 2004, NeuroImage.

[43]  L. Jäncke,et al.  The relation between forebrain volume and midsagittal size of the corpus callosum in children. , 1999, Neuroreport.

[44]  Jan Karbowski,et al.  How Does Connectivity Between Cortical Areas Depend on Brain Size? Implications for Efficient Computation , 2003, Journal of Computational Neuroscience.

[45]  David J. Willshaw,et al.  Competition for neurotrophic factor in the development of nerve connections , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

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

[47]  P. Rakić,et al.  Axon overproduction and elimination in the corpus callosum of the developing rhesus monkey , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  E. Courchesne,et al.  Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study , 2001, Neurology.

[49]  M H Van Kleeck,et al.  Hemispheric differences in global versus local processing of hierarchical visual stimuli by normal subjects: new data and a meta-analysis of previous studies. , 1989, Neuropsychologia.

[50]  H. J. Jerison.  Brain size and the evolution of mind , 1991 .

[51]  Martin I Sereno,et al.  The relation between connection length and degree of connectivity in young adults: a DTI analysis. , 2009, Cerebral cortex.

[52]  L. Mottron,et al.  Cognitive mechanisms, specificity and neural underpinnings of visuospatial peaks in autism. , 2006, Brain : a journal of neurology.

[53]  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.

[54]  Nagesh Adluru,et al.  Atypical diffusion tensor hemispheric asymmetry in autism , 2010, Autism research : official journal of the International Society for Autism Research.

[55]  Shingo Yamagata,et al.  Cerebral Asymmetry of the “Top-Down” Allocation of Attention to Global and Local Features , 2000, The Journal of Neuroscience.

[56]  S. Hevenor,et al.  The effect of variability of unattended information on global and local processing: evidence for lateralization at early stages of processing , 2000, Neuropsychologia.

[57]  A. Scheibel,et al.  Fiber composition of the human corpus callosum , 1992, Brain Research.

[58]  A. Schüz,et al.  Basic Connectivity of the Cerebral Cortex and some Considerations on the Corpus Callosum , 1996, Neuroscience & Biobehavioral Reviews.

[59]  E. Müller-Oehring,et al.  Contribution of Callosal Connections to the Interhemispheric Integration of Visuomotor and Cognitive Processes , 2010, Neuropsychology Review.

[60]  M. Behen,et al.  Alterations in frontal lobe tracts and corpus callosum in young children with autism spectrum disorder. , 2010, Cerebral cortex.

[61]  M. Cuccaro,et al.  Accelerated head growth in early development of individuals with autism. , 2005, Pediatric neurology.

[62]  E. Courchesne,et al.  When Is the Brain Enlarged in Autism? A Meta-Analysis of All Brain Size Reports , 2005, Biological Psychiatry.

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

[64]  R. Adler.  The Geometry of Random Fields , 2009 .

[65]  J. Mazziotta,et al.  Positron emission tomography study of human brain functional development , 1987, Annals of neurology.

[66]  W. Roberts,et al.  Language lateralization development in children with autism: Insights from the late field magnetoencephalogram , 2005, Neuroscience Letters.

[67]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[68]  Valentino Braitenberg,et al.  Brain Size and Number of Neurons: An Exercise in Synthetic Neuroanatomy , 2004, Journal of Computational Neuroscience.

[69]  H. Chugani.  A critical period of brain development: studies of cerebral glucose utilization with PET. , 1998, Preventive medicine.

[70]  S G Waxman,et al.  Conduction in myelinated, unmyelinated, and demyelinated fibers. , 1977, Archives of neurology.

[71]  Francisco Aboitiz,et al.  Species Differences and Similarities in the Fine Structure of the Mammalian Corpus callosum , 2001, Brain, Behavior and Evolution.

[72]  M. Just,et al.  Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. , 2007, Cerebral cortex.

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

[74]  D. Kaiser,et al.  Functional Connectivity and Aging: Comodulation and Coherence Differences , 2008 .

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

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

[77]  M. Just,et al.  Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. , 2004, Brain : a journal of neurology.

[78]  J H Miles,et al.  Head circumference is an independent clinical finding associated with autism. , 2000, American journal of medical genetics.

[79]  KJ Worsley,et al.  SurfStat: A Matlab toolbox for the statistical analysis of univariate and multivariate surface and volumetric data using linear mixed effects models and random field theory , 2009, NeuroImage.

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

[81]  R. Adler,et al.  Random Fields and Geometry , 2007 .

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

[83]  M. Reite,et al.  Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms , 2006, BMC psychiatry.