White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD and 44 typically developing (TD) age- and IQ-matched peers using diffusion tensor imaging. Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long-distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory.

[1]  Michael V. Lombardo,et al.  Impaired Communication Between the Motor and Somatosensory Homunculus Is Associated With Poor Manual Dexterity in Autism Spectrum Disorder , 2017, Biological Psychiatry.

[2]  A. Riecker,et al.  The contribution of white and gray matter differences to developmental dyslexia: Insights from DTI and VBM at 3.0T , 2008, Neuropsychologia.

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

[4]  D. Parker,et al.  Analysis of partial volume effects in diffusion‐tensor MRI , 2001, Magnetic resonance in medicine.

[5]  B. Leventhal,et al.  The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism , 2000, Journal of autism and developmental disorders.

[6]  Jacques-Donald Tournier,et al.  Diffusion tensor imaging and beyond , 2011, Magnetic resonance in medicine.

[7]  Moo K. Chung,et al.  A study of diffusion tensor imaging by tissue-specific, smoothing-compensated voxel-based analysis , 2009, NeuroImage.

[8]  Zhong Xue,et al.  Network‐based analysis reveals stronger local diffusion‐based connectivity and different correlations with oral language skills in brains of children with high functioning autism spectrum disorders , 2014, Human brain mapping.

[9]  Declan G. M. Murphy,et al.  Altered cerebellar feedback projections in Asperger syndrome , 2008, NeuroImage.

[10]  Mitchel S. Berger,et al.  Analysis of the subcomponents and cortical terminations of the perisylvian superior longitudinal fasciculus: a fiber dissection and DTI tractography study , 2012, Brain Structure and Function.

[11]  J. Michael Tyszka,et al.  Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant , 2006, NeuroImage.

[12]  Roberto Sacco,et al.  Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis , 2015, Psychiatry Research: Neuroimaging.

[13]  Byron Bernal,et al.  The connectivity of the superior longitudinal fasciculus: a tractography DTI study. , 2010, Magnetic resonance imaging.

[14]  Brian A. Wandell,et al.  Anatomical Properties of the Arcuate Fasciculus Predict Phonological and Reading Skills in Children , 2011, Journal of Cognitive Neuroscience.

[15]  P. Basser Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[16]  Xenophon Papademetris,et al.  Diffusion Tensor Imaging in Autism Spectrum Disorders: Preliminary Evidence of Abnormal Neural Connectivity , 2011, The Australian and New Zealand journal of psychiatry.

[17]  Stefan Skare,et al.  See Blockindiscussions, Blockinstats, Blockinand Blockinauthor Blockinprofiles Blockinfor Blockinthis Blockinpublication Extensive Blockinpiano Blockinpracticing Blockinhas Blockinregionally Specific Blockineffects Blockinon Blockinwhite Blockinmatter Blockindevelopment , 2022 .

[18]  Y. Nagakane,et al.  MR tractography depicting damage to the arcuate fasciculus in a patient with conduction aphasia , 2007, Neurology.

[19]  Maxime Descoteaux,et al.  Quantifying Brain Connectivity: A Comparative Tractography Study , 2009, MICCAI.

[20]  Rajesh K. Kana,et al.  The Implications of Brain Connectivity in the Neuropsychology of Autism , 2014, Neuropsychology Review.

[21]  A R Damasio,et al.  The anatomical basis of conduction aphasia. , 1980, Brain : a journal of neurology.

[22]  K. Hasan,et al.  Superior longitudinal fasciculus and cognitive dysfunction in adolescents born preterm and at term , 2010, Developmental medicine and child neurology.

[23]  J. Berman,et al.  Left Hemisphere Diffusivity of the Arcuate Fasciculus: Influences of Autism Spectrum Disorder and Language Impairment , 2014, American Journal of Neuroradiology.

[24]  T. Roberts,et al.  Elevated Mean Diffusivity in the Left Hemisphere Superior Longitudinal Fasciculus in Autism Spectrum Disorders Increases with More Profound Language Impairment , 2012, American Journal of Neuroradiology.

[25]  Luise Poustka,et al.  Fronto-temporal disconnectivity and symptom severity in children with autism spectrum disorder , 2012, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[26]  S. Tobimatsu,et al.  Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder , 2010, Brain Research.

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

[28]  D. Pandya,et al.  Association pathways of the prefrontal cortex and functional observations , 2002 .

[29]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[30]  Helen Tager-Flusberg,et al.  Structural asymmetries of language-related gray and white matter and their relationship to language function in young children with ASD , 2013, Brain Imaging and Behavior.

[31]  N. Geschwind The Organization of Language and the Brain: Language disorders after brain damage help in elucidating the neural basis of verbal behavior , 1970 .

[32]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[33]  Hangyi Jiang,et al.  Pediatric diffusion tensor imaging: Normal database and observation of the white matter maturation in early childhood , 2006, NeuroImage.

[34]  A. Dale,et al.  Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. , 2007, Brain : a journal of neurology.

[35]  C. Wheeler-Kingshott,et al.  About “axial” and “radial” diffusivities , 2009, Magnetic resonance in medicine.

[36]  Alan C. Evans,et al.  Growth patterns in the developing brain detected by using continuum mechanical tensor maps , 2000, Nature.

[37]  S. Baron-Cohen,et al.  The Autism Spectrum Quotient: Children’s Version (AQ-Child) , 2008, Journal of autism and developmental disorders.

[38]  Ralph-Axel Müller,et al.  Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder. , 2011, Journal of child psychology and psychiatry, and allied disciplines.

[39]  Derek K. Jones,et al.  Perisylvian language networks of the human brain , 2005, Annals of neurology.

[40]  Jason D. Yeatman,et al.  Language and reading skills in school-aged children and adolescents born preterm are associated with white matter properties on diffusion tensor imaging , 2012, Neuropsychologia.

[41]  H. Chugani,et al.  Sharp Curvature of Frontal Lobe White Matter Pathways in Children with Autism Spectrum Disorders: Tract-Based Morphometry Analysis , 2011, American Journal of Neuroradiology.

[42]  Gottfried Schlaug,et al.  Atypical hemispheric asymmetry in the arcuate fasciculus of completely nonverbal children with autism , 2012, Annals of the New York Academy of Sciences.

[43]  V. Wedeen,et al.  Fiber crossing in human brain depicted with diffusion tensor MR imaging. , 2000, Radiology.

[44]  Ross T. Whitaker,et al.  Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism , 2010, NeuroImage.

[45]  Friedemann Pulvermüller,et al.  Reduced Volume of the Arcuate Fasciculus in Adults with High-Functioning Autism Spectrum Conditions , 2016, Front. Hum. Neurosci..

[46]  L. Katz,et al.  Functional neuroimaging studies of reading and reading disability (developmental dyslexia). , 2000, Mental retardation and developmental disabilities research reviews.

[47]  Karl J. Friston,et al.  Generative and recognition models for neuroanatomy , 2004, NeuroImage.

[48]  B. Wandell,et al.  Children's Reading Performance is Correlated with White Matter Structure Measured by Diffusion Tensor Imaging , 2005, Cortex.

[49]  K. Lim,et al.  Age‐related decline in brain white matter anisotropy measured with spatially corrected echo‐planar diffusion tensor imaging , 2000, Magnetic resonance in medicine.

[50]  H. Tanabe,et al.  Conduction aphasia and arcuate fasciculus , 1987, Acta neurologica Scandinavica.

[51]  David E. Osher,et al.  Tracking the Roots of Reading Ability: White Matter Volume and Integrity Correlate with Phonological Awareness in Prereading and Early-Reading Kindergarten Children , 2013, The Journal of Neuroscience.

[52]  L. Lotspeich,et al.  White matter structure in autism: preliminary evidence from diffusion tensor imaging , 2004, Biological Psychiatry.

[53]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[54]  Do P. M. Tromp,et al.  Diffusion Tensor Imaging in Autism Spectrum Disorder: A Review , 2012, Autism research : official journal of the International Society for Autism Research.

[55]  N. Geschwind The organization of language and the brain. , 1970, Science.

[56]  P. Poulet,et al.  Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging , 2006, Journal of neuroscience research.

[57]  Derek K. Jones,et al.  White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults , 2010, Autism research : official journal of the International Society for Autism Research.

[58]  Derek K. Jones,et al.  Estimating the number of fiber orientations in diffusion MRI voxels : a constrained spherical deconvolution study , 2010 .

[59]  Alexander Leemans,et al.  Microstructural maturation of the human brain from childhood to adulthood , 2008, NeuroImage.

[60]  Fang-Cheng Yeh,et al.  Generalized ${ q}$-Sampling Imaging , 2010, IEEE Transactions on Medical Imaging.

[61]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[62]  Lauren E. Libero,et al.  Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders. , 2011, Physics of life reviews.

[63]  P. Basser,et al.  Comprehensive approach for correction of motion and distortion in diffusion‐weighted MRI , 2004, Magnetic resonance in medicine.

[64]  R. Wise,et al.  Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies. , 2003, British medical bulletin.

[65]  Mariana Lazar,et al.  Axonal deficits in young adults with High Functioning Autism and their impact on processing speed , 2014, NeuroImage: Clinical.

[66]  Hao Huang,et al.  Evidence of slow maturation of the superior longitudinal fasciculus in early childhood by diffusion tensor imaging , 2007, NeuroImage.

[67]  V. Wedeen,et al.  Generalized -Sampling Imaging , 2010 .

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

[69]  Bruce D. McCandliss,et al.  Neural systems predicting long-term outcome in dyslexia , 2010, Proceedings of the National Academy of Sciences.

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

[71]  Derek K. Jones,et al.  Occipito-temporal connections in the human brain. , 2003, Brain : a journal of neurology.

[72]  Carl-Fredrik Westin,et al.  White Matter Bundle Registration and Population Analysis Based on Gaussian Processes , 2011, IPMI.

[73]  F. Volkmar,et al.  Structural Neural Phenotype of Autism: Preliminary Evidence from a Diffusion Tensor Imaging Study Using Tract-Based Spatial Statistics , 2011, American Journal of Neuroradiology.

[74]  Khader M. Hasan,et al.  White matter development during late adolescence in healthy males: A cross-sectional diffusion tensor imaging study , 2007, NeuroImage.

[75]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[76]  Vicente L. Malave,et al.  Autism as a neural systems disorder: A theory of frontal-posterior underconnectivity , 2012, Neuroscience & Biobehavioral Reviews.

[77]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[78]  John O. Willis,et al.  Wechsler Abbreviated Scale of Intelligence , 2014 .

[79]  Hao Huang,et al.  White and gray matter development in human fetal, newborn and pediatric brains , 2006, NeuroImage.

[80]  Derek K. Jones,et al.  Spatial and orientational heterogeneity in the statistical sensitivity of skeleton-based analyses of diffusion tensor MR imaging data , 2011, Journal of Neuroscience Methods.

[81]  Katharine N. Thakkar,et al.  Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD) , 2008, Brain : a journal of neurology.

[82]  Seraphina Solders,et al.  Regional specificity of aberrant thalamocortical connectivity in autism , 2015, Human brain mapping.

[83]  C. Lebel,et al.  Longitudinal Development of Human Brain Wiring Continues from Childhood into Adulthood , 2011, The Journal of Neuroscience.

[84]  Christine Ecker,et al.  Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan , 2015, The Lancet Neurology.

[85]  Timothy D. Verstynen,et al.  Deterministic Diffusion Fiber Tracking Improved by Quantitative Anisotropy , 2013, PloS one.

[86]  R. Poldrack,et al.  Microstructure of Temporo-Parietal White Matter as a Basis for Reading Ability Evidence from Diffusion Tensor Magnetic Resonance Imaging , 2000, Neuron.

[87]  Riva Ariella The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults: An International Validation Study , 2011 .

[88]  Steven D Chen,et al.  The Superior Longitudinal Fasciculus in Typically Developing Children and Adolescents , 2015, Journal of child neurology.

[89]  Thomas E. Nichols,et al.  Nonparametric Permutation Tests for Functional Neuroimaging , 2003 .

[90]  B. Wandell,et al.  Tract Profiles of White Matter Properties: Automating Fiber-Tract Quantification , 2012, PloS one.

[91]  Anders Dale,et al.  White matter microstructure correlates of narrative production in typically developing children and children with high functioning autism , 2013, Neuropsychologia.

[92]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[93]  D. Pandya,et al.  Segmentation of subcomponents within the superior longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study. , 2005, Cerebral cortex.

[94]  Moo K. Chung,et al.  Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism , 2007, Neuroscience Letters.

[95]  M. Just,et al.  A developmental study of the structural integrity of white matter in autism , 2007, Neuroreport.