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）的人能够流利地使用口语，也经常在言语的超片段方面（韵律）存在问题。ASD个体在韵律方面的困难会影响接受性和表达性语言。韵律对言语交际所传递的“个人”信息有重要贡献，使个体能够参与到有社会意义和有效话语的共同建构中。ASD的韵律感知困难可能与导致自闭症综合症其他症状领域的相同神经发育缺陷有关。目前流行的观点是，ASD的这些缺陷可能与远程神经连接异常有关。重要的是，目前所有关于韵律的生物学理论都认为，理解韵律依赖于广泛分离的大脑区域的动态整合过程。我们认为，ASD患者理解韵律的困难实际上可能与处理韵律所需的大脑区域之间的连接异常有关。然而，迄今为止，关于理解ASD韵律的研究还很有限，特别是关于个体感知情感韵律线索（言语中的“情绪”）和理解其重要性的能力。本课题的研究目标是：1)更好地表征高功能自闭症个体（HFA）在理解情感韵律方面的知觉障碍，2)识别区分高功能自闭症个体与对照组的情感韵律知觉任务的功能神经解剖学，3)确定神经连接异常是否可以解释(2)中发现的功能神经解剖学差异。4)可能有助于开发有用的内表型标记物，有助于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磁共振成像（fMRI）来评估从已建立的ASD研究对象库中招募的兄弟姐妹对以及对照受试者对不同情感韵律的言语刺激做出感知判断的反应。除了在fMRI数据中对大脑激活进行更常规的评估外，我们将首次在自闭症研究中评估不同的反应类型（短暂反应和持续反应），并联合应用三种不同的技术来评估大脑结构、功能连接和脑网络中的白质束完整性。将确定这些技术识别的功能和连接“异常”之间的对应强度。我们的兄弟姐妹对实验设计也将提供初步识别可能在家庭中聚集的“标记”的机会，这可能对未来的遗传评估很重要。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患者的一些沟通障碍，特别是那些涉及理解个体之间口头表达情感的障碍。然而，这个项目的结果也可能丰富我们对情感和语言交流的其他个人方面如何被正常人理解的理解，并阐明这些过程在人脑中被破坏的机制。

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.