Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD.

[1]  L. Lotspeich,et al.  Similar white matter aberrations in children with autism and their unaffected siblings: a diffusion tensor imaging study using tract-based spatial statistics. , 2010, Archives of general psychiatry.

[2]  F. A. Karnes,et al.  Comparison of Intelligence Tests , 1987 .

[3]  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.

[4]  M. Just,et al.  Functional connectivity in a baseline resting-state network in autism , 2006, Neuroreport.

[5]  Dietmar Cordes,et al.  Role of the corpus callosum in functional connectivity. , 2003, AJNR. American journal of neuroradiology.

[6]  Alexander Leemans,et al.  The B‐matrix must be rotated when correcting for subject motion in DTI data , 2009, Magnetic resonance in medicine.

[7]  David R. Rowland.  The brain that changes itself: Stories of personal triumph from the frontiers of brain science , 2010 .

[8]  A. Goldman.  To Appear in: , 2008 .

[9]  Alan Connelly,et al.  Robust determination of the fibre orientation distribution in diffusion MRI: Non-negativity constrained super-resolved spherical deconvolution , 2007, NeuroImage.

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

[11]  J. Belliveau,et al.  White matter integrity and pictorial reasoning in high-functioning children with autism , 2010, Brain and Cognition.

[12]  Derek K. Jones,et al.  RESTORE: Robust estimation of tensors by outlier rejection , 2005, Magnetic resonance in medicine.

[13]  D. Shukla,et al.  White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study. , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  A. Leemans,et al.  Microstructural White Matter Abnormalities and Cognitive Functioning in Type 2 Diabetes , 2012, Diabetes Care.

[15]  I. Koerte,et al.  Diffusion Tensor Imaging , 2014 .

[16]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[17]  Jason J. S. Barton,et al.  Reduced cognitive control of response inhibition by the anterior cingulate cortex in autism spectrum disorders , 2010, NeuroImage.

[18]  V. Wedeen,et al.  Mapping fiber orientation spectra in cerebral white matter with Fourier-transform diffusion MRI , 2000 .

[19]  M. Lowe,et al.  Resting state sensorimotor functional connectivity in multiple sclerosis inversely correlates with transcallosal motor pathway transverse diffusivity , 2008, Human brain mapping.

[20]  Max A. Viergever,et al.  The influence of complex white matter architecture on the mean diffusivity in diffusion tensor MRI of the human brain , 2012, NeuroImage.

[21]  Max A. Viergever,et al.  Partial volume effect as a hidden covariate in DTI analyses , 2011, NeuroImage.

[22]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[23]  Derek K. Jones,et al.  Temporal association tracts and the breakdown of episodic memory in mild cognitive impairment , 2012, Neurology.

[24]  Alan Connelly,et al.  Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution , 2004, NeuroImage.

[25]  Mark T. Waters,et al.  This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.Thislicensedoesnot permit commercial exploitation or the creation of derivative works without sp , 2009 .

[26]  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.

[27]  M. Just,et al.  Sentence comprehension in autism: thinking in pictures with decreased functional connectivity. , 2006, Brain : a journal of neurology.

[28]  Timothy Edward John Behrens,et al.  Training induces changes in white matter architecture , 2009, Nature Neuroscience.

[29]  Max A. Viergever,et al.  Mutual-information-based registration of medical images: a survey , 2003, IEEE Transactions on Medical Imaging.

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

[31]  M. Just,et al.  Altering Cortical Connectivity: Remediation-Induced Changes in the White Matter of Poor Readers , 2009, Neuron.

[32]  O Sporns,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009, Proceedings of the National Academy of Sciences.

[33]  S. Arridge,et al.  Detection and modeling of non‐Gaussian apparent diffusion coefficient profiles in human brain data , 2002, Magnetic resonance in medicine.

[34]  Uta Frith,et al.  Theory of mind , 2001, Current Biology.

[35]  Mara Cercignani,et al.  Twenty‐five pitfalls in the analysis of diffusion MRI data , 2010, NMR in biomedicine.

[36]  Klaas E. Stephan,et al.  Neurophysiological correlates of relatively enhanced local visual search in autistic adolescents , 2007, NeuroImage.

[37]  Chandan J. Vaidya,et al.  Atypical neural substrates of Embedded Figures Task performance in children with Autism Spectrum Disorder , 2007, NeuroImage.

[38]  A. Couteur,et al.  Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders , 1994, Journal of autism and developmental disorders.

[39]  M. Just,et al.  Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task , 2010, Autism research : official journal of the International Society for Autism Research.

[40]  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.

[41]  Scott Peltier,et al.  Abnormalities of intrinsic functional connectivity in autism spectrum disorders, , 2009, NeuroImage.

[42]  N. Bargalló,et al.  Brain Effects of Cognitive Remediation Therapy in Schizophrenia: A Structural and Functional Neuroimaging Study , 2013, Biological Psychiatry.

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

[44]  B. Jeurissen,et al.  Improved Sensitivity to Cerebral White Matter Abnormalities in Alzheimer’s Disease with Spherical Deconvolution Based Tractography , 2012, PloS one.

[45]  D. Wechsler.  Wechsler Intelligence Scale for Children , 2020, Definitions.

[46]  Carl-Fredrik Westin,et al.  Processing and visualization for diffusion tensor MRI , 2002, Medical Image Anal..

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

[48]  M. P. van den Heuvel,et al.  Microstructural Organization of the Cingulum Tract and the Level of Default Mode Functional Connectivity , 2008, The Journal of Neuroscience.

[49]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[50]  Marcel Adam Just,et al.  Theory of Mind disruption and recruitment of the right hemisphere during narrative comprehension in autism , 2008, Neuropsychologia.

[51]  Jeremy D. Schmahmann,et al.  Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers , 2008, NeuroImage.

[52]  L. Frank.  Characterization of anisotropy in high angular resolution diffusion‐weighted MRI , 2002, Magnetic resonance in medicine.

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

[54]  Christopher S. Monk,et al.  Alterations of resting state functional connectivity in the default network in adolescents with autism spectrum disorders , 2010, Brain Research.

[55]  D. Finkelhor,et al.  ADMINISTRATION AND SCORING MANUAL , 2001 .

[56]  Robert T. Schultz,et al.  Involvement of the anterior thalamic radiation in boys with high functioning autism spectrum disorders: A Diffusion Tensor Imaging study , 2011, Brain Research.

[57]  Diane C. Chugani,et al.  Diffusion Tensor Imaging of Frontal Lobe in Autism Spectrum Disorder , 2008, Cerebral cortex.

[58]  Jan Sijbers,et al.  Probabilistic fiber tracking using the residual bootstrap with constrained spherical deconvolution , 2011, Human brain mapping.

[59]  Katherine A. Johnson,et al.  White Matter and Visuospatial Processing in Autism: A Constrained Spherical Deconvolution Tractography Study , 2013, Autism research : official journal of the International Society for Autism Research.

[60]  Teresa K. W. Wong,et al.  White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

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

[62]  Scott T. Grafton,et al.  Structural foundations of resting-state and task-based functional connectivity in the human brain , 2013, Proceedings of the National Academy of Sciences.

[63]  David G. Norris,et al.  An Investigation of Functional and Anatomical Connectivity Using Magnetic Resonance Imaging , 2002, NeuroImage.

[64]  Katherine A. Johnson,et al.  Atypical Visuospatial Processing in Autism: Insights from Functional Connectivity Analysis , 2012, Autism research : official journal of the International Society for Autism Research.

[65]  Chun-Hung Yeh,et al.  Resolving crossing fibres using constrained spherical deconvolution: Validation using diffusion-weighted imaging phantom data , 2008, NeuroImage.

[66]  Vince D. Calhoun,et al.  Measuring brain connectivity: Diffusion tensor imaging validates resting state temporal correlations , 2008, NeuroImage.

[67]  Justin L. Vincent,et al.  Precuneus shares intrinsic functional architecture in humans and monkeys , 2009, Proceedings of the National Academy of Sciences.

[68]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[69]  P. Boesiger,et al.  SENSE: Sensitivity encoding for fast MRI , 1999, Magnetic resonance in medicine.

[70]  Biyu J. He,et al.  Loss of Resting Interhemispheric Functional Connectivity after Complete Section of the Corpus Callosum , 2008, The Journal of Neuroscience.

[71]  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.

[72]  Derek K. Jones,et al.  Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging , 2013, Human brain mapping.

[73]  Haiqing Huang,et al.  Detecting abnormalities of corpus callosum connectivity in autism using magnetic resonance imaging and diffusion tensor tractography , 2011, Psychiatry Research: Neuroimaging.

[74]  Marlene Behrmann,et al.  The anatomy of the callosal and visual-association pathways in high-functioning autism: A DTI tractography study , 2011, Cortex.

[75]  Max A. Viergever,et al.  elastix: A Toolbox for Intensity-Based Medical Image Registration , 2010, IEEE Transactions on Medical Imaging.

[76]  Jan Sijbers,et al.  ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data , 2009 .

[77]  Timothy E. J. Behrens,et al.  Human connectomics , 2012, Current Opinion in Neurobiology.