Emotion-Modulated Psychophysiology of Autism Spectrum Disorders

描述（由申请人提供）：本提案的框架是，社会认知缺陷和限制性重复行为的典型自闭症症状可能都以对情感刺激的目标导向反应失调为特征。因此，我们假设失调的神经生物学机制介导方法和戒断动机可能是这两个看似不同的症状域的基础。有人认为，调节不良的动机反应是其他疾病的核心特征，这一概念已经取得了丰硕成果，因为目标导向行为的神经生物学基础已经在动物模型、人类非临床环境和人类病理生理状态中得到了广泛研究。此外，由于动机状态失调与特定神经递质系统异常功能之间建立了联系，这些研究已经成功地为其他疾病提供了新颖有效的治疗方法。我们建议利用成熟的动机状态的心理生理测量来评估基于神经生物学的防御和食欲系统对与自闭症行为表型相关的情感刺激的启动。具体而言，我们建议测量心理生理反应的情感调节：(1)规范性情感刺激；(2)孤独症个体的社会刺激和(3)限制性兴趣刺激。最重要的相关性将是惊吓眨眼和耳后反射反应的情感调节，因为在理论基础上，它们非常适合评估对社会和限制兴趣刺激的反应特征，而这些刺激是自闭症的核心特征。该项目也代表了NICHD发展障碍研究中心的两位新成员（北卡罗来纳大学的Dichter博士和范德比尔特大学的Benning博士）之间的首次合作，并汇集了自闭症行为表型，心理生理学和儿童发育方面的专家，以研究表征自闭症内表型的新方法。公共卫生相关性：本项目旨在通过无痛和非侵入性的心理生理测量来更好地了解自闭症的病理生理学。从这项研究中获得的信息将允许未来的研究调查这些心理生理测量是否具有诊断效用，以及它们是否可以作为治疗反应的生物标志物。

DESCRIPTION (provided by applicant): The framework of this proposal is that the classic autism symptoms of social-cognitive deficits and restricted repetitive behaviors may both be characterized by dysregulated goal-directed responses to affective stimuli. Thus, we hypothesize that dysregulated neurobiological mechanisms mediating approach and withdrawal motivation may underlie these two seemingly disparate symptom domains. It has been argued that poorly modulated motivational responses are core features of other disorders, a conceptualization that has been fruitful because the neurobiological basis of goal-directed behaviors has been extensively studied in animal models, in human nonclinical contexts, and in human pathophysiological states. Additionally, because of established linkages between dysregulated motivational states and aberrant functioning of specific neurotransmitter systems, these lines of research have been successful in suggesting novel and effective treatment approaches in other disorders. We propose to leverage well-established psychophysiological measures of motivational states to assess the priming of neurobiologically-based defensive and appetitive systems in response to affective stimuli relevant to the autism behavioral phenotype. Specifically, we propose to measure affective modulation of psychophysiological responses to: (1) normative affective stimuli; (2) social stimuli, and (3) restricted interest stimuli in individuals with autism. Of prime relevance will be affective modulation of the startle eyeblink and postauricular reflex responses because, on theoretical grounds, they are ideally suited for assessing the response characteristics to social and restricted interest stimuli that are core features of autism. The project also represents an initial collaboration between two new members of NICHD Developmental Disabilities Research Centers (co-PI's Dr. Dichter at the University of North Carolina and Dr. Benning at Vanderbilt University) and brings together experts in the autism behavioral phenotype, psychophysiology, and child development to investigate a novel approach to characterizing the autism endophenotype. PUBLIC HEALTH RELEVANCE: This project seeks to better understand the pathophysiology of autism using painless and noninvasive psychophysiological measures. The information learned from this study would allow for future research that investigates whether these psychophysiological measures may have diagnostic utility and whether they may serve as biomarkers of treatment response.