Autism Spectrum Disorder Related Functional Connectivity Changes in the Language Network in Children, Adolescents and Adults

Autism spectrum disorder (ASD) is a neurodevelopmental disability with global implication. Altered brain connectivity in the language network has frequently been reported in ASD patients using task-based functional magnetic resonance imaging (fMRI) compared to typically developing (TD) participants. Most of these studies have focused on a specific age group or mixed age groups with ASD. In the current study, we investigated age-related changes in functional connectivity related measure, degree centrality (DC), in the language network across three age groups with ASD (113 children, 113 adolescents and 103 adults) using resting-state fMRI data collected from the autism brain imaging data exchange repository. We identified regions with significant group-wise differences between ASD and TD groups for three age cohorts using DC based on graph theory. We found that both children and adolescents with ASD showed decreased DC in Broca’s area compared to age-matched TD groups. Adults with ASD showed decreased DC in Wernicke’s area compared to TD adults. We also observed increased DC in the left inferior parietal lobule (IPL) and left middle temporal gyrus (MTG) for children with ASD compared to TD children and for adults with ASD compared to TD adults, respectively. Overall, functional differences occurred in key language processing regions such as the left inferior frontal gyrus (IFG) and superior temporal gyrus (STG) related to language production and comprehension across three age cohorts. We explored correlations between DC values of our findings with autism diagnostic observation schedule (ADOS) scores related to severity of ASD symptoms in the ASD group. We found that DC values of the left IFG demonstrated negative correlations with ADOS scores in children and adolescents with ASD. The left STG showed significant negative correlations with ADOS scores in adults with ASD. These results might shed light on the language network regions that should be further explored for prognosis, diagnosis, and monitoring of ASD in three age groups.

[1]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[2]  J. Buitelaar,et al.  The phenotype and neural correlates of language in autism: An integrative review , 2008, Neuroscience & Biobehavioral Reviews.

[3]  On neural systems for speech and song in autism. , 2012, Brain : a journal of neurology.

[4]  Nouchine Hadjikhani,et al.  fMRI activation during a language task in adolescents with ASD , 2008, Journal of the International Neuropsychological Society.

[5]  T. Q. Irigaray,et al.  Intellectual abilities in Alzheimer's disease patients: Contributions from the Wechsler Abbreviated Scale of Intelligence (WASI) , 2010 .

[6]  Thomas E. Nichols,et al.  Functional connectomics from resting-state fMRI , 2013, Trends in Cognitive Sciences.

[7]  S. Holm A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[8]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[9]  M. Dapretto,et al.  Neural basis of irony comprehension in children with autism: the role of prosody and context. , 2006, Brain : a journal of neurology.

[10]  Elizabeth Redcay,et al.  Deviant Functional Magnetic Resonance Imaging Patterns of Brain Activity to Speech in 2–3-Year-Old Children with Autism Spectrum Disorder , 2008, Biological Psychiatry.

[11]  Ralph-Axel Müller,et al.  Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders. , 2011, Cerebral cortex.

[12]  C. Haselgrove,et al.  Connectivity in Autism: A Review of MRI Connectivity Studies , 2015, Harvard review of psychiatry.

[13]  Ralph-Axel Müller,et al.  Atypical network connectivity for imitation in autism spectrum disorder , 2010, Neuropsychologia.

[14]  B. Luna,et al.  Age related changes in striatal resting state functional connectivity in autism , 2013, Front. Hum. Neurosci..

[15]  Yong He,et al.  Graph Theoretical Analysis of Functional Brain Networks: Test-Retest Evaluation on Short- and Long-Term Resting-State Functional MRI Data , 2011, PloS one.

[16]  L. Lagae,et al.  Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum☆ , 2014, NeuroImage: Clinical.

[17]  Alan C. Evans,et al.  Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans , 2009, PloS one.

[18]  Oliver Grimm,et al.  Test–retest reliability of fMRI-based graph theoretical properties during working memory, emotion processing, and resting state , 2014, NeuroImage.

[19]  Natalie L. Colich,et al.  Atypical Neural Processing of Ironic and Sincere Remarks in Children and Adolescents with Autism Spectrum Disorders , 2012, Metaphor and symbol.

[20]  John D. E. Gabrieli,et al.  Intrinsic functional network organization in high-functioning adolescents with autism spectrum disorder , 2013, Front. Hum. Neurosci..

[21]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[22]  C. Price The anatomy of language: contributions from functional neuroimaging , 2000, Journal of anatomy.

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

[24]  Eva K Ritzl,et al.  The fMRI success rate of children and adolescents: Typical development, epilepsy, attention deficit/hyperactivity disorder, and autism spectrum disorders , 2009, Human brain mapping.

[25]  M. Just,et al.  Brain Function Differences in Language Processing in Children and Adults with Autism , 2013, Autism research : official journal of the International Society for Autism Research.

[26]  Vince D. Calhoun,et al.  Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients , 2010, NeuroImage.

[27]  Jun-Sung Park,et al.  Whole-brain Functional Networks in Cognitively Normal, Mild Cognitive Impairment, and Alzheimer’s Disease , 2013, PloS one.

[28]  Justin L. Vincent,et al.  Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

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

[30]  Yanmei Tie,et al.  Defining language networks from resting‐state fMRI for surgical planning—a feasibility study , 2014, Human brain mapping.

[31]  C. Chabris,et al.  Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging , 2006, Brain and Cognition.

[32]  Mark W. Woolrich,et al.  FSL , 2012, NeuroImage.

[33]  D. Shukla,et al.  Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity. , 2013, Brain : a journal of neurology.

[34]  Rafael Malach,et al.  Disrupted Neural Synchronization in Toddlers with Autism , 2011, Neuron.

[35]  Patricia Howlin,et al.  Outcome in High-Functioning Adults with Autism with and Without Early Language Delays: Implications for the Differentiation Between Autism and Asperger Syndrome , 2003, Journal of autism and developmental disorders.

[36]  Carl D. Hacker,et al.  Clustering of Resting State Networks , 2012, PloS one.

[37]  Vivek Prabhakaran,et al.  Functional connectivity changes in the language network during stroke recovery , 2015, Annals of clinical and translational neurology.

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

[39]  P. Hagoort,et al.  Neural correlates of pragmatic language comprehension in autism spectrum disorders. , 2009, Brain : a journal of neurology.

[40]  Клинические дисциплины Autism Diagnostic Observation Schedule , 2010 .

[41]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[42]  Alan C. Evans,et al.  Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. , 2007, Cerebral cortex.

[43]  Geraldine Dawson,et al.  Abnormal functional connectivity in autism spectrum disorders during face processing. , 2008, Brain : a journal of neurology.

[44]  Daniel P. Kennedy,et al.  The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism , 2013, Molecular Psychiatry.

[45]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[46]  John J. Foxe,et al.  Topological organization of the “small-world” visual attention network in children with attention deficit/hyperactivity disorder (ADHD) , 2013, Front. Hum. Neurosci..

[47]  J. Bogen,et al.  WERNICKE'S REGION–WHERE IS IT? , 1976, Annals of the New York Academy of Sciences.

[48]  Michael S. Gaffrey,et al.  A typical participation of visual cortex during word processing in autism: An fMRI study of semantic decision , 2007, Neuropsychologia.

[49]  Karl J. Friston,et al.  Movement‐Related effects in fMRI time‐series , 1996, Magnetic resonance in medicine.

[50]  R. Müller The study of autism as a distributed disorder. , 2007, Mental retardation and developmental disabilities research reviews.

[51]  Byron Bernal,et al.  How Localized are Language Brain Areas? A Review of Brodmann Areas Involvement in Oral Language. , 2016, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[52]  E. Ross Cerebral Localization of Functions and the Neurology of Language: Fact versus Fiction or Is It Something Else? , 2010, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[53]  Jessica R. Jones,et al.  Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011-2012. , 2013, National health statistics reports.

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

[55]  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.

[56]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[57]  J. Rauschecker,et al.  Maps and streams in the auditory cortex: nonhuman primates illuminate human speech processing , 2009, Nature Neuroscience.