Reduced functional connectivity within and between ‘social’ resting state networks in autism spectrum conditions

Individuals with Autism Spectrum Conditions (ASC) have difficulties in social interaction and communication, which is reflected in hypoactivation of brain regions engaged in social processing, such as medial prefrontal cortex (mPFC), amygdala and insula. Resting state studies in ASC have identified reduced connectivity of the default mode network (DMN), which includes mPFC, suggesting that other resting state networks incorporating ‘social’ brain regions may also be abnormal. Using Seed-based Connectivity and Group Independent Component Analysis (ICA) approaches, we looked at resting functional connectivity in ASC between specific ‘social’ brain regions, as well as within and between whole networks incorporating these regions. We found reduced functional connectivity within the DMN in individuals with ASC, using both ICA and seed-based approaches. Two further networks identified by ICA, the salience network, incorporating the insula and a medial temporal lobe network, incorporating the amygdala, showed reduced inter-network connectivity. This was underlined by reduced seed-based connectivity between the insula and amygdala. The results demonstrate significantly reduced functional connectivity within and between resting state networks incorporating ‘social’ brain regions. This reduced connectivity may result in difficulties in communication and integration of information across these networks, which could contribute to the impaired processing of social signals in ASC.

[1]  U. Frith Mind Blindness and the Brain in Autism , 2001, Neuron.

[2]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[3]  S. Rombouts,et al.  Reduced resting-state brain activity in the "default network" in normal aging. , 2008, Cerebral cortex.

[4]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[5]  HighWire Press Philosophical Transactions of the Royal Society of London , 1781, The London Medical Journal.

[6]  Daniel P. Kennedy,et al.  Functional abnormalities of the default network during self- and other-reflection in autism. , 2008, Social cognitive and affective neuroscience.

[7]  Vince D. Calhoun,et al.  A review of group ICA for fMRI data and ICA for joint inference of imaging, genetic, and ERP data , 2009, NeuroImage.

[8]  L. Uddin,et al.  Functional Brain Correlates of Social and Nonsocial Processes in Autism Spectrum Disorders: An Activation Likelihood Estimation Meta-Analysis , 2009, Biological Psychiatry.

[9]  Daniel P. Kennedy,et al.  The intrinsic functional organization of the brain is altered in autism , 2008, NeuroImage.

[10]  Rex E. Jung,et al.  A Baseline for the Multivariate Comparison of Resting-State Networks , 2011, Front. Syst. Neurosci..

[11]  E. Bullmore,et al.  Differential activation of the amygdala and the ‘social brain’ during fearful face-processing in Asperger Syndrome , 2007, Neuropsychologia.

[12]  S. Baron-Cohen,et al.  Screening Adults for Asperger Syndrome Using the AQ: A Preliminary Study of its Diagnostic Validity in Clinical Practice , 2005, Journal of autism and developmental disorders.

[13]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[14]  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.

[15]  E. Bullmore,et al.  Social intelligence in the normal and autistic brain: an fMRI study , 1999, The European journal of neuroscience.

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

[17]  R. Kahn,et al.  Functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain , 2009, Human brain mapping.

[18]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

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

[20]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C. Frith,et al.  Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. , 2002, Brain : a journal of neurology.

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

[23]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

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

[25]  V. Haughton,et al.  Frequencies contributing to functional connectivity in the cerebral cortex in "resting-state" data. , 2001, AJNR. American journal of neuroradiology.

[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]  J. Pekar,et al.  On the relationship between seed‐based and ICA‐based measures of functional connectivity , 2011, Magnetic resonance in medicine.

[28]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[29]  Vince D. Calhoun,et al.  A method for functional network connectivity among spatially independent resting-state components in schizophrenia , 2008, NeuroImage.

[30]  K. Davis,et al.  Two systems of resting state connectivity between the insula and cingulate cortex , 2009, Human brain mapping.

[31]  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.

[32]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[33]  Geoffrey Bird,et al.  Levels of emotional awareness and autism: An fMRI study , 2008, Social neuroscience.

[34]  Roel M. Willems,et al.  Altered intrinsic functional connectivity of anterior and posterior insula regions in high‐functioning participants with autism spectrum disorder , 2011, Human brain mapping.

[35]  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.

[36]  S. Baron-Cohen,et al.  The Autism-Spectrum Quotient (AQ): Evidence from Asperger Syndrome/High-Functioning Autism, Malesand Females, Scientists and Mathematicians , 2001, Journal of autism and developmental disorders.

[37]  Thomas E. Nichols,et al.  Power calculation for group fMRI studies accounting for arbitrary design and temporal autocorrelation , 2008, NeuroImage.

[38]  G. McCarthy,et al.  Neural basis of eye gaze processing deficits in autism. , 2005, Brain : a journal of neurology.

[39]  Tülay Adali,et al.  Estimating the number of independent components for functional magnetic resonance imaging data , 2007, Human brain mapping.

[40]  C. Lord,et al.  Aberrant Striatal Functional Connectivity in Children with Autism , 2011, Biological Psychiatry.

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

[42]  M. Corbetta,et al.  The Reorienting System of the Human Brain: From Environment to Theory of Mind , 2008, Neuron.

[43]  M. Corbetta,et al.  Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex , 1997, Journal of Cognitive Neuroscience.

[44]  D. Povinelli,et al.  Mindblindness. An Essay on Autism and Theory of Mind Simon Baron-Cohen 1995 , 1996, Trends in Neurosciences.

[45]  Stephen M Smith,et al.  Correspondence of the brain's functional architecture during activation and rest , 2009, Proceedings of the National Academy of Sciences.

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

[47]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[48]  J. Pekar,et al.  A method for making group inferences from functional MRI data using independent component analysis , 2001, Human brain mapping.

[49]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[50]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

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

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

[53]  Daniel P. Kennedy,et al.  Failing to deactivate: resting functional abnormalities in autism. , 2006, Proceedings of the National Academy of Sciences of the United States of America.