Autonomic and brain responses associated with empathy deficits in autism spectrum disorder

Accumulating evidence suggests that autonomic signals and their cortical representations are closely linked to emotional processes, and that related abnormalities could lead to social deficits. Although socio‐emotional impairments are a defining feature of autism spectrum disorder (ASD), empirical evidence directly supporting the link between autonomic, cortical, and socio‐emotional abnormalities in ASD is still lacking. In this study, we examined autonomic arousal indexed by skin conductance responses (SCR), concurrent cortical responses measured by functional magnetic resonance imaging, and effective brain connectivity estimated by dynamic causal modeling in seventeen unmedicated high‐functioning adults with ASD and seventeen matched controls while they performed an empathy‐for‐pain task. Compared to controls, adults with ASD showed enhanced SCR related to empathetic pain, along with increased neural activity in the anterior insular cortex, although their behavioral empathetic pain discriminability was reduced and overall SCR was decreased. ASD individuals also showed enhanced correlation between SCR and neural activities in the anterior insular cortex. Importantly, significant group differences in effective brain connectivity were limited to greater reduction in the negative intrinsic connectivity of the anterior insular cortex in the ASD group, indicating a failure in attenuating anterior insular responses to empathetic pain. These results suggest that aberrant interoceptive precision, as indexed by abnormalities in autonomic activity and its central representations, may underlie empathy deficits in ASD. Hum Brain Mapp 36:3323–3338, 2015. © 2015 The Authors Human Brain Mapping Published byWiley Periodicals, Inc.

[1]  M. Behrmann,et al.  Seeing it differently: visual processing in autism , 2006, Trends in Cognitive Sciences.

[2]  H. Critchley,et al.  Visceral Influences on Brain and Behavior , 2013, Neuron.

[3]  V. Ramachandran,et al.  Autonomic responses of autistic children to people and objects , 2001, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[4]  Xiaosi Gu,et al.  Attention and reality constraints on the neural processes of empathy for pain , 2007, NeuroImage.

[5]  Nicole R. Zürcher,et al.  Emotional contagion for pain is intact in autism spectrum disorders , 2014, Translational Psychiatry.

[6]  A. Craig Significance of the insula for the evolution of human awareness of feelings from the body. , 2011, Annals of the New York Academy of Sciences.

[7]  U. Frith The 38th Sir Frederick Bartlett Lecture Why we need cognitive explanations of autism , 2012, Quarterly journal of experimental psychology.

[8]  Simon Baron-Cohen,et al.  Absence of Embodied Empathy During Pain Observation in Asperger Syndrome , 2009, Biological Psychiatry.

[9]  Karl J. Friston,et al.  Comparing Families of Dynamic Causal Models , 2010, PLoS Comput. Biol..

[10]  Karl J. Friston,et al.  Anterior insular cortex and emotional awareness , 2013, The Journal of comparative neurology.

[11]  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.

[12]  Stephen W Porges,et al.  Electroencephalogram and heart rate regulation to familiar and unfamiliar people in children with autism spectrum disorders. , 2009, Child development.

[13]  Jin Fan,et al.  Abnormal autonomic and associated brain activities during rest in autism spectrum disorder. , 2014, Brain : a journal of neurology.

[14]  P. Ekman,et al.  Autonomic nervous system activity distinguishes among emotions. , 1983, Science.

[15]  Karl J. Friston The free-energy principle: a unified brain theory? , 2010, Nature Reviews Neuroscience.

[16]  O. J. Dunn Multiple Comparisons among Means , 1961 .

[17]  Lucina Q. Uddin,et al.  The anterior insula in autism: Under-connected and under-examined , 2009, Neuroscience & Biobehavioral Reviews.

[18]  Karl J. Friston,et al.  Computational psychiatry: the brain as a phantastic organ. , 2014, The lancet. Psychiatry.

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

[20]  H. Critchley,et al.  An Interoceptive Predictive Coding Model of Conscious Presence , 2011, Front. Psychology.

[21]  Jin Fan,et al.  Functional Dissociation of the Frontoinsular and Anterior Cingulate Cortices in Empathy for Pain , 2010, The Journal of Neuroscience.

[22]  Karl J. Friston,et al.  Modelling event-related skin conductance responses , 2010, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[23]  Raymond J. Dolan,et al.  The anatomy of choice: active inference and agency , 2013, Front. Hum. Neurosci..

[24]  A. Craig How Do You Feel?: An Interoceptive Moment with Your Neurobiological Self , 2014 .

[25]  R. Turner,et al.  Event-Related fMRI: Characterizing Differential Responses , 1998, NeuroImage.

[26]  Naomi B. Pitskel,et al.  Neural signatures of autism , 2010, Proceedings of the National Academy of Sciences.

[27]  Karl J. Friston,et al.  Attention, Uncertainty, and Free-Energy , 2010, Front. Hum. Neurosci..

[28]  Karl J. Friston,et al.  Bayesian model selection for group studies , 2009, NeuroImage.

[29]  G. Rizzolatti,et al.  Both of Us Disgusted in My Insula The Common Neural Basis of Seeing and Feeling Disgust , 2003, Neuron.

[30]  E. Ziegel,et al.  Bootstrapping: A Nonparametric Approach to Statistical Inference , 1993 .

[31]  John L Bradshaw,et al.  Visuospatial processing and the function of prefrontal-parietal networks in autism spectrum disorders: a functional MRI study. , 2006, The American journal of psychiatry.

[32]  U. Frith,et al.  Vagaries of Visual Perception in Autism , 2005, Neuron.

[33]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[34]  H. Critchley,et al.  A common role of insula in feelings, empathy and uncertainty , 2009, Trends in Cognitive Sciences.

[35]  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.

[36]  J. Hart,et al.  Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. , 2003, Brain research. Cognitive brain research.

[37]  J. Wagemans,et al.  Precise minds in uncertain worlds: predictive coding in autism. , 2014, Psychological review.

[38]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[39]  Anneli Kylliäinen,et al.  Skin Conductance Responses to Another Person’s Gaze in Children with Autism , 2006, Journal of autism and developmental disorders.

[40]  Adam Smith The Empathy Imbalance Hypothesis of Autism: A Theoretical Approach to Cognitive and Emotional Empathy in Autistic Development , 2009 .

[41]  U. Frith,et al.  Cognitive explanations of autism , 1996, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[42]  Karl J. Friston,et al.  Canonical Microcircuits for Predictive Coding , 2012, Neuron.

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

[44]  Fabrizio Benedetti,et al.  A comprehensive review of the placebo effect: recent advances and current thought. , 2008, Annual review of psychology.

[45]  Keith M. Shafritz,et al.  The Neural Circuitry Mediating Shifts in Behavioral Response and Cognitive Set in Autism , 2008, Biological Psychiatry.

[46]  D. Burr,et al.  When the world becomes ‘too real’: a Bayesian explanation of autistic perception , 2012, Trends in Cognitive Sciences.

[47]  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.

[48]  George Mendelson,et al.  Book Reviews , 1995 .

[49]  H. Critchley,et al.  The Embodiment of Emotional Feelings in the Brain , 2010, The Journal of Neuroscience.

[50]  David J. Heeger,et al.  Unreliable Evoked Responses in Autism , 2012, Neuron.

[51]  J. Decety,et al.  The functional architecture of human empathy. , 2004, Behavioral and cognitive neuroscience reviews.

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

[53]  Rafael Malach,et al.  Face-selective Activation in a Congenital Prosopagnosic Subject , 2003, Journal of Cognitive Neuroscience.

[54]  S. Preston,et al.  Empathy: Its ultimate and proximate bases. , 2001, The Behavioral and brain sciences.

[55]  F. D. de Waal Putting the altruism back into altruism: the evolution of empathy. , 2008, Annual review of psychology.

[56]  Geoffrey Bird,et al.  Attention does not modulate neural responses to social stimuli in autism spectrum disorders , 2006, NeuroImage.

[57]  Claus Lamm,et al.  Is the extrastriate body area (EBA) sensitive to the perception of pain in others? , 2008, Cerebral cortex.

[58]  Karl J. Friston,et al.  Modelling functional integration: a comparison of structural equation and dynamic causal models , 2004, NeuroImage.

[59]  J. Decety,et al.  Empathic arousal and social understanding in individuals with autism: evidence from fMRI and ERP measurements. , 2014, Social cognitive and affective neuroscience.

[60]  Karl J. Friston,et al.  Ten simple rules for dynamic causal modeling , 2010, NeuroImage.

[61]  U. Frith,et al.  Empathic brain responses in insula are modulated by levels of alexithymia but not autism , 2010, Brain : a journal of neurology.

[62]  R. Turner,et al.  Characterizing Evoked Hemodynamics with fMRI , 1995, NeuroImage.

[63]  S. Baron-Cohen,et al.  The Empathy Quotient: An Investigation of Adults with Asperger Syndrome or High Functioning Autism, and Normal Sex Differences , 2004, Journal of autism and developmental disorders.

[64]  Pearl H. Chiu,et al.  Self Responses along Cingulate Cortex Reveal Quantitative Neural Phenotype for High-Functioning Autism , 2008, Neuron.

[65]  Jean Decety,et al.  Empathy and judging other's pain: an fMRI study of alexithymia. , 2007, Cerebral cortex.

[66]  J. G. Snodgrass,et al.  Pragmatics of measuring recognition memory: applications to dementia and amnesia. , 1988, Journal of experimental psychology. General.

[67]  Karl J. Friston,et al.  On Hyperpriors and Hypopriors: Comment on Pellicano and Burr , 2022 .

[68]  Karl J. Friston,et al.  Neuroscience and Biobehavioral Reviews , 2014 .

[69]  Karl J. Friston,et al.  Human Neuroscience Hypothesis and Theory Article an Aberrant Precision Account of Autism , 2022 .

[70]  R. Saxe Uniquely human social cognition , 2006, Current Opinion in Neurobiology.

[71]  U. Frith,et al.  The Weak Coherence Account: Detail-focused Cognitive Style in Autism Spectrum Disorders , 2006, Journal of autism and developmental disorders.

[72]  A. Wagner,et al.  Annals of the New York Academy of Sciences Cognitive Control and Right Ventrolateral Prefrontal Cortex: Reflexive Reorienting, Motor Inhibition, and Action Updating , 2022 .

[73]  A. Seth Interoceptive inference, emotion, and the embodied self , 2013, Trends in Cognitive Sciences.

[74]  Thomas H. B. FitzGerald,et al.  Interoceptive inference: homeostasis and decision-making , 2014, Trends in Cognitive Sciences.

[75]  Jin Fan,et al.  Cognition-emotion integration in the anterior insular cortex. , 2013, Cerebral cortex.

[76]  Lizabeth M Romanski,et al.  Representation and integration of auditory and visual stimuli in the primate ventral lateral prefrontal cortex. , 2007, Cerebral cortex.

[77]  Hugo D. Critchley,et al.  Interoceptive Basis to Craving , 2007, Neuron.

[78]  Patrik Vuilleumier,et al.  Felt and Seen Pain Evoke the Same Local Patterns of Cortical Activity in Insular and Cingulate Cortex , 2011, The Journal of Neuroscience.

[79]  Jin Fan,et al.  Spontaneous Brain Activity Relates to Autonomic Arousal , 2012, The Journal of Neuroscience.

[80]  F. Happé,et al.  Time to give up on a single explanation for autism , 2006, Nature Neuroscience.

[81]  Jin Fan,et al.  Anterior insular cortex is necessary for empathetic pain perception. , 2012, Brain : a journal of neurology.

[82]  G J Taylor,et al.  The Twenty-item Toronto Alexithymia Scale--II. Convergent, discriminant, and concurrent validity. , 1994, Journal of psychosomatic research.

[83]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[84]  A. Damasio,et al.  Basic emotions are associated with distinct patterns of cardiorespiratory activity. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.