Testing the hyperspecificity hypothesis: a neural theory of autism

描述（由申请人提供）：自闭症谱系障碍（ASD）中的核心功能障碍在于物体的感知表征和物体特征之间的全局关系的假设已经成为ASD的几个非常突出的理论的核心，包括“弱中央一致性”（Frith，1989; Happ <$& Frith 2006）和“减少泛化”（Plaisted，2001）解释。尽管这些理论在文献中的流行和长寿，但在验证或实例化它们与潜在的神经机制方面几乎没有取得成功。弥合认知科学和大脑机制之间的鸿沟是ASD研究的一个重大障碍，实验方法的创新至关重要。超特异性假说（McClelland，2000）为这样一个桥梁奠定了框架，表明对象或事件的稀疏，较少相互连接的表征通过减少灵活理解世界所需的神经关系来驱动ASD的认知功能改变。神经编码方案存在于沿着一个广度的频谱中。在最稀疏的编码极端是对象和事件的独立“祖母”单元表示。在这个连续体的另一端是最大限度地重叠的“分布式”代码。ASD处理的超特异性假设预测，与正常发育个体的更广泛表征相比，ASD个体的视觉感知神经代码更稀疏、重叠更少。这种“窄调谐”（Gustafsson，1997）具有ASD经典表型特征的直接理论推论，包括识别面部身份和表情的困难。目前的提议代表了有史以来第一次对ASD“超特异性”假设的神经测试。测试包括 我们的实验室开发的用于功能磁共振成像和ERP的新方法的应用。我们预测，功能磁共振成像为基础的探针将揭示稀疏的神经编码在ASD，和编码稀疏的指数将与赤字的面孔识别测试。这种追求是第一个将ASD的可行网络假设与实验可测试的神经实例联系起来的方法之一。这一发现将推动未来对这些疾病的神经病因学的研究，为评估遗传、发育和学习对感知过程的相互作用提供神经立足点。此外，我们的建议有可能通过阐明核心神经机制来为治疗提供信息，这些机制可以成为新干预措施的重点。

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.