The Role of the Amygdala in Autism

描述（由申请人提供）：该指导临床科学家奖的总体目标是让申请人发展必要的专业知识，这对于自闭症儿童杏仁核功能的神经生物学评估至关重要。来自K08奖的资金将允许减少临床责任，并使候选人能够进行一系列旨在为转化临床研究的职业发展提供重要背景的研究。培训计划的核心组成部分是神经成像方面的指导，因为它与自闭症儿童的社会情感功能有关。申请人的长期目标是发展一个独立的情感神经科学研究计划，将神经心理学和神经影像学的方法应用于自闭症儿童的研究和治疗。包括神经病理学、损伤研究和神经影像学在内的多条研究路线提供了共同的证据，表明杏仁核与自闭症的发病机制有关。这个提议的一个中心假设是，杏仁核的失调导致自闭症的各种障碍，包括对潜在威胁刺激的反应增加，内隐和外显情绪感知的缺陷以及有限的社会行为。 因此，我们的主要研究目标是使用已建立的杏仁核功能磁共振成像探针来评估其在自闭症中的功能状态。这些实验包括激活杏仁核的任务，这些任务涉及一系列处理技能，从基本的情感信息编码到社会知识和判断。我们提出，在自闭症儿童中存在一种分离，即杏仁核在基本的威胁检测中过度活跃，但在复杂的社会情境中，杏仁核并不承担向其他大脑区域（如额叶）传达社会情感相关性和背景的计算要求更高的角色。如果这是真的，那么自闭症患者的杏仁核可能会导致对社会情境的错误感知，因为他们无法准确地解读社会线索，从而导致在社会情境中做出不恰当的行为反应。

DESCRIPTION (provided by applicant): The overarching goal of this Mentored Clinical Scientist Award is to allow the applicant to develop requisite expertise that is essential for conducting neurobiological assessments of amygdala function in children with autism. Funds from the K08 award would allow reduction of clinical responsibilities and enable the candidate to pursue a series of investigations that are designed to provide an important context for career development in translational clinical research. The central component of the training program is mentorship in neuroimaging as it relates to the socioemotional functioning of children with autism. The long-term goal of the applicant is to develop an independent affective neuroscience research program that applies the methods of neuropsychology and neuroimaging to the study and treatment of children with autism. Several Lines of research including neuropathology, lesion studies, and neuroimaging have provided converging evidence implicating the amygdala in the pathogenesis of autism. A central hypothesis of this proposal is that dysregulation of the amygdala contributes to various impairments in autism including increased response to potentially threatening stimuli, deficits in implicit and explicit emotion perception, and limited social behavior. Our main research objective, therefore, is to use established fMRI probes of the amygdala to evaluate its functional status in autism. The experiments include tasks that activate the amygdala across a range of processing skills from basic encoding of emotional information to social knowledge and judgment. We propose that a disassociation exists in children with autism such that the amygdala is hyperactive in the basic detection of threat but does not serve the computationally more demanding role of conveying socioemotional relevance and context to other brain regions, such as the frontal lobe, during complex social situations. If true, the autistic amygdala might lead to the misperception of social situations through a failure to accurately read social cues resulting in inappropriate behavioral responding in social situations.