NEUROBIOLOGY OF AFFECTIVE PROSODY PERCEPTION IN AUTISM

描述（由申请人提供）：即使患有自闭症谱系障碍（ASD）的个体能够流利地使用口语，也经常存在言语的超分段方面（韵律）的问题。自闭症患者在韵律方面的困难会影响语言的接受性和表达性。韵律在言语交际中传递的“个人”信息中起着重要的作用，它使个体能够参与到有社会意义和有效的话语的共同构建中。ASD患者的韵律感知困难可能与导致自闭症综合征其他症状领域的神经发育缺陷有关。目前流行的观点是，ASD中的这些缺陷可能涉及远程神经连接的异常。重要的是，所有目前的韵律生物学理论都认为韵律的理解取决于广泛分离的大脑区域中过程的动态整合。我们建议，在理解自闭症的韵律的困难，事实上，可能与潜在的异常，其处理所需的大脑区域之间的连接。然而，迄今为止，对ASD中韵律理解的研究有限，特别是关于个体感知情感韵律线索（言语中的“情感”）并理解其意义的能力。本提案中的研究目标是：1）更好地表征高功能自闭症个体（HFA）理解情感韵律的知觉障碍，2）识别情感韵律知觉任务的功能神经解剖学，其显著区分HFA与对照受试者，3）确定神经连接的异常是否可以解释（2）中确定的功能性神经解剖学的差异，和4）潜在地有助于开发有用的内表型标记物，其可以帮助识别自闭症的遗传和神经生物学原因。为了实现这些目标，在这个为期两年的项目中，我们将使用行为测试和功能性磁共振成像（fMRI）来评估从一个既定的ASD研究对象池招募的同胞对的反应，以及那些控制对象，因为他们对语音刺激的感知判断不同的情感韵律。除了在功能磁共振成像数据中对大脑激活进行更传统的评估外，我们将首次在自闭症研究中评估不同的反应类型（瞬时与持续反应），并联合应用三种独立的技术来评估我们的受试者参与的大脑网络中的大脑结构，功能连接和白色物质束完整性。将确定用这些技术确定的功能和连接“异常”之间的对应强度。我们的同胞对实验设计也将提供机会，初步确定可能的“标记”，聚集在家庭，这可能是重要的未来的遗传评估。这个为期两年的脑成像项目的首要目标是确定大脑中的异常连接是否可以解释自闭症的一些沟通障碍，特别是那些涉及理解个体之间口头表达的情感的障碍。然而，这个项目的结果也可能丰富我们对情感和言语交流的其他个人方面如何被正常人理解的理解，并澄清这些过程在人类大脑中被破坏的机制。

DESCRIPTION (provided by applicant): Even individuals with autism spectrum disorders (ASD) who develop fluent use of spoken language often sustain problems with the suprasegmental aspects of speech (prosody). ASD individuals' difficulties with prosody can affect receptive as well as expressive language. Prosody contributes significantly to the `personal' information conveyed by speech communication that enables individuals to participate in the joint construction of socially meaningful and effective discourse. Difficulties in perception of prosody in ASD may be related to the same neurodevelopmental deficits that result in other symptomatic domains of the autistic syndrome. A currently popular view is that these deficits in ASD may involve abnormalities in long-range neural connectivity. Importantly, all current biological theories of prosody view understanding prosody as depending upon the dynamic integration of processes in widely- separated brain regions. We propose that difficulties in understanding prosody in ASD may, in fact, be related to underlying abnormalities in connectivity among brain regions required for its processing. Limited research has been done on understanding prosody in ASD to date, however, particularly with regard to individuals' abilities to perceive affective prosodic cues (the 'emotion' in speech) and understand their significance. The goals of the research in this proposal are: 1) to better characterize the perceptual impairment in understanding affective prosody in high-functioning autistic individuals (HFA), 2) to identify the functional neuroanatomy of an affective prosody perceptual task that significantly distinguishes HFA from control subjects, 3) to determine whether abnormalities in neural connectivity may explain the differences in functional neuroanatomy identified in (2), and 4) to potentially contribute to the development of a useful endophenotypic marker that may aid in identification of genetic and neurobiological causes of autism. To achieve these goals, in this two-year project we will use behavioral testing and functional magnetic resonance imaging (fMRI) to assess the responses of sib-pairs recruited from an established ASD research subject pool as well as those of control subjects as they make perceptual judgments on speech stimuli varying in their affective prosody. In addition to more conventional assessments of brain activation within the fMRI data, we will for the first time in a study of autism assess distinct response types (transient vs. sustained responses) and jointly apply three separate techniques for assessing brain structure, functional connectivity and white matter tract integrity in brain networks engaged by our subjects. The strength of correspondence between functional and connectional 'abnormalities' identified with these techniques will be determined. Our sib-pair experimental design will also offer the opportunity for preliminarily identifying possible `markers' that aggregate in families, which may be important for future genetic evaluations. An overarching goal of this two-year brain imaging project is to determine whether abnormal connections in the brain may account for some of the communication impairments in autism, particularly those involved in the understanding of verbally expressed emotion between individuals. Results of this project, however, may also enrich our understanding of how emotion and other personal aspects of verbal communication are understood by normal individuals, and clarify mechanisms by which these processes can be disrupted in the human brain.