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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\u2010functioning adults with ASD and seventeen matched controls while they performed an empathy\u2010for\u2010pain 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. <jats:italic>Hum Brain Mapp 36:3323\u20133338, 2015<\/jats:italic>. \u00a9 <jats:bold>2015 The Authors Human Brain Mapping Published byWiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.22840","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T12:01:24Z","timestamp":1432209684000},"page":"3323-3338","source":"Crossref","is-referenced-by-count":103,"title":["Autonomic and brain responses associated with empathy deficits in autism spectrum disorder"],"prefix":"10.1002","volume":"36","author":[{"given":"Xiaosi","family":"Gu","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Neuroimaging, University College London London United Kingdom"},{"name":"Virignia Tech Carilion Research Institute Roanoke 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