Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults.

OBJECTIVE The Social Responsiveness Scale-Adult Version (SRS-A) measures autistic traits that are continuously distributed in the general population. Based on increased recognition of the dimensional nature of autistic traits, the authors examined the neural correlates of these traits in neurotypical individuals using the SRS-A and established a novel approach to assessing the neural basis of autistic characteristics, attempting to directly relate SRS-A scores to patterns of functional connectivity observed in the pregenual anterior cingulate cortex, a region commonly implicated in social cognition. METHOD Resting state functional magnetic resonance imaging scans were collected for 25 neurotypical adults. All participants provided SRS-A ratings completed by an informant who had observed them in natural social settings. Whole brain-corrected connectivity analyses were then conducted using SRS-A scores as a covariate of interest. RESULTS Across participants, a significant negative relationship between SRS-A scores and the functional connectivity of the pregenual anterior cingulate cortex with the anterior portion of the mid-insula was found. Specifically, low levels of autistic traits were observed when a substantial portion of the anterior mid-insula showed positive connectivity with the pregenual anterior cingulate cortex. In contrast, elevated levels of autistic traits were associated with negative connectivity between these two regions. CONCLUSIONS Resting state functional connectivity of the pregenual anterior cingulate cortex-insula social network was related to autistic traits in neurotypical adults. Application of this approach in samples with autism spectrum disorders is needed to confirm whether this circuit is dimensionally related to the severity of autistic traits in clinical populations.

[1]  S. Folstein,et al.  Infantile autism: a genetic study of 21 twin pairs. , 1977, Journal of child psychology and psychiatry, and allied disciplines.

[2]  M. Mesulam,et al.  Insula of the old world monkey. Architectonics in the insulo‐orbito‐temporal component of the paralimbic brain , 1982, The Journal of comparative neurology.

[3]  J R Augustine,et al.  The insular lobe in primates including humans. , 1985, Neurological research.

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

[5]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[6]  J. Constantino,et al.  Reciprocal Social Behavior in Children With and Without Pervasive Developmental Disorders , 2000, Journal of developmental and behavioral pediatrics : JDBP.

[7]  S. Baron-Cohen,et al.  The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. , 2001, Journal of child psychology and psychiatry, and allied disciplines.

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

[9]  J. Constantino,et al.  Validation of a Brief Quantitative Measure of Autistic Traits: Comparison of the Social Responsiveness Scale with the Autism Diagnostic Interview-Revised , 2003, Journal of autism and developmental disorders.

[10]  J. Constantino,et al.  Autistic traits in the general population: a twin study. , 2003, Archives of general psychiatry.

[11]  C. Frith,et al.  Functional imaging of ‘theory of mind’ , 2003, Trends in Cognitive Sciences.

[12]  Jonathan D. Cohen,et al.  The Neural Basis of Economic Decision-Making in the Ultimatum Game , 2003, Science.

[13]  F. Bermpohl,et al.  Cortical midline structures and the self , 2004, Trends in Cognitive Sciences.

[14]  H. Critchley,et al.  Neural systems supporting interoceptive awareness , 2004, Nature Neuroscience.

[15]  Viv Bewick,et al.  Statistics review 10: Further nonparametric methods , 2004, Critical care.

[16]  Stephanie Hayes,et al.  The factor structure of autistic traits. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

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

[18]  J. Constantino,et al.  Intergenerational transmission of subthreshold autistic traits in the general population , 2005, Biological Psychiatry.

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

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

[21]  Stephen Lawrie,et al.  Functional Specialization within Rostral Prefrontal Cortex (Area 10): A Meta-analysis , 2006, Journal of Cognitive Neuroscience.

[22]  C. Frith,et al.  Meeting of minds: the medial frontal cortex and social cognition , 2006, Nature Reviews Neuroscience.

[23]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[24]  T. Singer The neuronal basis and ontogeny of empathy and mind reading: Review of literature and implications for future research , 2006, Neuroscience & Biobehavioral Reviews.

[25]  Justin L. Vincent,et al.  Disruption of Large-Scale Brain Systems in Advanced Aging , 2007, Neuron.

[26]  G. Dawson,et al.  Resting State Cortical Connectivity Reflected in EEG Coherence in Individuals With Autism , 2007, Biological Psychiatry.

[27]  Randy L. Buckner,et al.  Unrest at rest: Default activity and spontaneous network correlations , 2007, NeuroImage.

[28]  N. Minshew,et al.  The new neurobiology of autism: cortex, connectivity, and neuronal organization. , 2007, Archives of neurology.

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

[30]  Aaron C. Koralek,et al.  Two Takes on the Social Brain: A Comparison of Theory of Mind Tasks , 2007, Journal of Cognitive Neuroscience.

[31]  Daniel S. Margulies,et al.  Mapping the functional connectivity of anterior cingulate cortex , 2007, NeuroImage.

[32]  Joseph Piven,et al.  The Broad Autism Phenotype Questionnaire , 2007, Journal of autism and developmental disorders.

[33]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

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

[35]  V. Menon,et al.  A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks , 2008, Proceedings of the National Academy of Sciences.

[36]  D. Margulies,et al.  Development of anterior cingulate functional connectivity from late childhood to early adulthood. , 2009, Cerebral cortex.

[37]  Elliot T. Berkman,et al.  Correlations in Social Neuroscience Aren't Voodoo: Commentary on Vul et al. (2009) , 2009, Perspectives on psychological science : a journal of the Association for Psychological Science.

[38]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[39]  Elliot T. Berkman,et al.  Correlations in Social Neuroscience Aren't Voodoo , 2009 .

[40]  B. Biswal,et al.  The resting brain: unconstrained yet reliable. , 2009, Cerebral cortex.

[41]  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.

[42]  Daniel S. Margulies,et al.  Functional connectivity of the human amygdala using resting state fMRI , 2009, NeuroImage.

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