Multimodal Neuroimaging of Prosody in Schizophrenia and Developmental Disorders

描述(由申请人提供)：无法通过声音调制(韵律)传达情感是患有各种神经精神疾病(如精神分裂症和自闭症)的患者社会认知功能障碍的一个主要方面。这些缺陷的神经机制，以及它们是如何从童年发展到成年的，得到的研究非常少。这项培训计划旨在使候选人为解决这两个问题的独立研究做好准备。在韵律的神经机制方面，有一些证据表明，韵律功能障碍与颞叶和额叶皮质之间的相互作用中断有关。这个回路的时间部分似乎分析声音信号中的情绪区别，然后由额叶成分评估情感意义。这一回路很可能介导了精神分裂症患者的韵律功能障碍，这与基本的听觉感觉障碍和异常的颞额相互作用有关。这里提出的研究将使用多模式神经成像方法，通过整合三种最先进的神经成像技术，在健康成年人和精神分裂症患者中首次对这一颞额回路进行全面描述。首先，脑磁图(MEG)结合磁共振功能连接分析(FMRI)将被用来确定电路处理的时间进程。然后，通过应用扩散成像，这些功能估计将与听觉通路完整性的神经结构估计相关联。我们希望证明在精神分裂症的韵律处理过程中，神经结构完整性缺陷是异常的颞额相互作用的基础。除了多模式神经成像方面的培训外，拟议的活动还将为候选人提供语言和听觉神经生物学发展心理学方面的背景知识，以及为儿童和青少年开发和调整韵律任务的框架。应聘者是宾夕法尼亚大学的精神病学讲师，对社交有着既定的兴趣。蒂莫西·罗伯茨博士和鲁本·古尔将指导他。罗伯茨博士是脑磁图和DTI技术方面的专家，主要研究健康儿童和自闭症患者的听觉和语言处理能力。古尔博士是神经心理评估和神经成像方面的专家，他的研究涉及精神分裂症患者的情绪和认知功能障碍。这些导师将保证，拟议的培训计划带来的经验将使候选人能够建立一个独立的研究项目，该项目可以在社会沟通的发展神经科学领域做出重大贡献，并了解这种沟通障碍是如何在精神分裂症和自闭症等神经精神障碍中出现的。

DESCRIPTION (provided by applicant): An inability to convey emotion by vocal modulation (prosody) is a major aspect of social cognitive dysfunction for patients afflicted with a variety of neuropsychiatric illnesses such as schizophrenia and autism. The neural mechanisms of these deficits, and how they develop from childhood to adulthood have received remarkably little research attention. This training proposal seeks to prepare the candidate for independent research that addresses both of these issues. In terms of the neural mechanisms of prosody, there is some evidence that prosodic dysfunction is associated with a disruption of interactions between temporal and frontal cortex. The temporal component of this circuit appears to parse the acoustic signal for emotional distinctions, which are subsequently evaluated for emotional meaning by the frontal component. It is likely that this circuit mediates prosodic dysfunction in schizophrenia, which is associated with basic audio-sensory deficits and abnormal temporo-frontal interactions. The research proposed here will employ multimodal neuroimaging approaches to produce the first comprehensive description of this temporo-frontal circuit, in both healthy adults and patients with schizophrenia, by integrating three state-of-the-art neuroimaging techniques. First, magnetoencephalography (MEG) in conjunction with magnetic resonance functional connectivity analysis (fMRI) will be used to determine the time course of processing by the circuit. Then, by applying Diffusion Imaging, these functional estimates will be related to neurostructural estimates of auditory pathway integrity. We expect to demonstrate that neurostructural integrity deficits underpin abnormal temporo-frontal interactions during prosodic processing in schizophrenia. In addition to training the candidate in multimodal neuroimaging, the proposed activities will provide him a background in the developmental psychology of language and auditory neurobiology, as well as a framework to develop and adapt prosodic tasks for children and adolescents. The candidate is an Instructor in Psychiatry at the University of Pennsylvania and has an established interest in social communication. Drs. Timothy Roberts and Ruben Gur will mentor him. Dr. Roberts is an expert in MEG and DTI techniques, with a research focus on the development of auditory and language processing in healthy children and patients with autism. Dr. Gur is an expert in neuropsychological assessment and neuroimaging, whose research concerns emotional and cognitive dysfunction in schizophrenia. These mentors will assure that the experience resulting from the proposed training plan will enable the candidate to establish an independent research program that can make significant contributions in the developmental neuroscience of social communication, and the understanding of how dysfunction in such communication emerges in neuropsychiatric disorders like schizophrenia and autism.