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）的核心功能障碍在于物体感知表征和物体特征之间的整体关系，这一假设是几个非常突出的ASD理论的核心，包括“弱中心一致性”（Frith, 1989; Happ¿& Frith 2006）和“减少泛化”（Plaisted, 2001）。尽管这些理论在文献中很受欢迎，寿命也很长，但在验证或实例化它们的潜在神经机制方面却取得了很少的成功。弥合认知科学和大脑机制之间的鸿沟是自闭症谱系障碍研究的一个重大障碍，实验方法的创新是必不可少的。高特异性假说（McClelland, 2000）为这种桥梁搭建了框架，表明对物体或事件的更稀疏、更少相互联系的表征通过减少对世界的灵活理解所必需的神经关系，驱动了ASD认知功能的改变。神经编码方案的存在范围很广。在最小的编码极端是独立的“祖母”单元表示对象和事件。在这个连续体的另一端是最大程度重叠的“分布式”代码。ASD加工的高特异性假说预测，与典型发育个体的广泛表征相比，ASD个体的视觉感知神经编码更少，重叠更少。这种“更窄的调谐”（Gustafsson, 1997）与ASD的经典表型特征有直接的理论推论，包括识别面部身份和表情的困难。目前的提议代表了ASD“高特异性”假说的第一个神经测试。测试包括

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.