Testing the hyperspecificity hypothesis: a neural theory of autism

检验超特异性假说：自闭症的神经理论

• 批准号: 8514729
• 负责人: ROBERT Thomas SCHULTZ
• 金额: $ 18.98万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514729
• 关键词: Accounting; Address; Adult; Area; Autistic Disorder; Behavioral; Binding; Biological; Brain; Cells; Code; Cognitive; Cognitive Science; Data; Development; Discrimination; Disease; Etiology; Event; Face; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genetic; Goals; Individual; Influentials; Intervention; Investigation; Learning; Link; Literature; Longevity; Measurement; Measures; Methodology; Methods; Mind; Perception; Plant Roots; Population; Population Control; Population Heterogeneity; Process; Research; Scheme; Stimulus; Testing; Visual; Visual Perception; Work; autism spectrum disorder; base; behavior measurement; central coherence; cognitive function; design; developmental disease; disorder control; flexibility; foot; fusiform face area; indexing; innovation; neuroadaptation; neuroimaging; neuromechanism; novel; relating to nervous system; response; success; theories

DESCRIPTION (provided by applicant): The hypothesis that a core dysfunction in autism spectrum disorders (ASD) lies in the global relationships between perceptual representations of objects and object features has been central to several very prominent theories of ASD, including the "weak central coherence" (Frith, 1989; Happ¿ & Frith 2006) and "reduced generalization" (Plaisted, 2001) accounts. Despite the popularity and longevity of these theories in the literature, little success has been achieved in validating or instantiating them with respec to underlying neural mechanisms. Bridging this divide between cognitive science and brain mechanism represents a significant hurdle in ASD research, and innovation in experimental approach is essential. The hyperspecificity hypothesis (McClelland, 2000) lays the framework for just such a bridge, suggesting that sparser, less inter-connected representation of objects or events drives altered cognitive functioning in ASD by reducing the neural relationships necessary for a flexible understanding of the world. Neural encoding schemes exist along a spectrum of breadth. At sparest coding extreme are independent "grandmother" cell representations for objects and events. At the other end of this continuum are maximally overlapping "distributed" codes. The hyperspecificity hypothesis of ASD processing predicts sparser, lesser overlapping neural codes for visual perception among individuals with ASD compared to broader representations in typically developing individuals. Such "narrower tuning" (Gustafsson, 1997) has direct theoretical corollaries to the classical phenotypic features of ASD, including difficulties recognizing facial identities and expressions. The current proposal represents the first ever neural test of the "hyperspecificity" hypothesis of ASD. Testing involves application of new methods that our labs developed for implementation with fMRI and ERPs. We predict that fMRI based probe will reveal sparser neural encoding in ASD, and that indices of encoding sparseness will correlate with deficits on face recognition tests. This pursuit is one of the first to link a viable network hypothesis of ASD to an experimentally testable neural instantiation. Such a finding would propel future research into the neural etiology of the disorders, offering a neural foothold for evaluating the interactions of genetics, development and learning on the process of perception. Further, our proposal has the potential to inform treatment by elucidating the core neural mechanisms that can be the focus of new interventions.

描述（由应用程序提供）：假设自闭症谱系障碍（ASD）的核心功能障碍在于对象的感知表示和对象特征之间的全球关系对于ASD的几种非常重要的ASD理论至关重要，包括“弱中心相干性”（Frith，1989; 1989; Happ＆Frith 2006;Happ®＆Frith 2006 and“降低了一般性的责任”（Plaisted centriped''（plaissed），2001年），2001年，2001年issist issistsistsistsistsistsistsisist ascissist ascissist ascissists 2001。尽管这些理论在文献中具有流行和寿命，但在验证或实例化基础神经机制方面几乎没有成功。桥接认知科学和大脑机制之间的这种鸿沟代表了ASD研究中的一个重大障碍，实验方法的创新至关重要。超特定性假设（McClelland，2000）为仅仅是这样的桥梁建立了框架，这表明对物体或事件的稀疏，较少相互连接的表示通过减少对世界的灵活理解所必需的神经关系，从而改变了ASD的认知功能。神经编码方案沿着广度范围存在。在最稀少的编码中，极端是对象和事件的独立“祖母”细胞表示。在另一端继续，继续将“分布式”代码重叠。与典型发展的个体相比，ASD处理预测预测预测的高度特异性假设较为稀疏，与典型发育中的个体相比，ASD患者的视觉感知的重叠较少。这种“狭窄的调整”（Gustafsson，1997）将理论推论带到了ASD的经典表型特征，包括识别面部身份和表达的困难。当前的提议代表了ASD的“超特定性”假设的首次中性检验。测试涉及 我们的实验室开发了用于使用fMRI和ERP实施的新方法的应用。我们预测，基于fMRI的探针将揭示ASD中的较为稀疏的神经编码，并且编码稀疏性的指标将与面部识别测试的定义相关。这种追求是最早将ASD可行网络假设与实验测试的神经元实例联系起来的追求之一。这样的发现将推动未来的研究对疾病的神经病因，从而为评估遗传学，发展和学习在感知过程中的相互作用提供了神经立足。此外，我们的建议有可能通过阐明可能是新干预措施的重点的核心神经元机制来为治疗提供信息。