Testing the hyperspecificity hypothesis: a neural theory of autism

描述(申请人提供)：自闭症谱系障碍(ASD)的核心功能障碍存在于对物体的知觉表征和物体特征之间的全局关系的假设一直是自闭症谱系障碍(ASD)的几个非常突出的理论的核心，包括“弱中心连贯性”(Frith，1989；Happ&Frith 2006)和“概化程度降低”(Plaisted，2001)。尽管这些理论在文献中广受欢迎且经久不衰，但在用潜在的神经机制来验证或实例化它们方面几乎没有取得什么成功。弥合认知科学和脑机制之间的这种鸿沟是自闭症研究中的一个重大障碍，实验方法的创新是必不可少的。多特异性假说(McClelland，2000)奠定了这样一座桥梁的框架，认为对对象或事件的更稀疏、更少相互关联的表征通过减少灵活理解世界所需的神经关系来驱动ASD认知功能的改变。神经编码方案沿着广度的频谱存在。最极端的编码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加工的高特异性假说预测，与典型发育个体中更广泛的表征相比，ASD个体中视觉感知的神经编码更稀疏、重叠更少。这种“更窄的调谐”(Gustafsson，1997)直接从理论上推论了自闭症的典型表型特征，包括识别面部身份和表情的困难。目前的建议是首次对ASD的“高特异性”假说进行神经测试。测试涉及到 应用我们实验室为实施功能磁共振成像和事件相关电位而开发的新方法。我们预测，基于fMRI的探针将揭示ASD中更稀疏的神经编码，编码稀疏性的指数将与人脸识别测试中的缺陷相关。这是第一个将ASD的可行网络假说与可通过实验测试的神经实例化联系起来的研究之一。这样的发现将推动未来对这些疾病的神经病因学的研究，为评估感知过程中遗传、发育和学习的相互作用提供一个神经立足点。此外，我们的建议有可能通过阐明可以成为新干预重点的核心神经机制来为治疗提供信息。

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.