Multimodal Neuroimaging of Prosody in Schizophrenia and Developmental Disorders

描述（由申请人提供）：无法通过声音调节（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）的患者的社会认知功能障碍的主要方面。这些缺陷的神经机制，以及它们如何从童年发展到成年，受到的研究关注非常少。这项培训计划旨在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。该回路的时间部分似乎解析了声学信号的情感区别，随后由额叶部分评估情感意义。这可能是这个电路介导的韵律功能障碍，精神分裂症，这是与基本的听觉缺陷和异常的颞额互动。这里提出的研究将采用多模态神经成像方法，通过整合三种最先进的神经成像技术，在健康成人和精神分裂症患者中首次全面描述颞额电路。首先，脑磁图（MEG）结合磁共振功能连接分析（fMRI）将用于确定电路处理的时间过程。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。我们希望证明，神经结构的完整性缺陷的基础异常颞额叶的相互作用在韵律处理精神分裂症。除了培训候选人在多模态神经成像，拟议的活动将为他提供语言和听觉神经生物学的发展心理学的背景，以及一个框架，以开发和适应儿童和青少年的韵律任务。候选人是宾夕法尼亚大学的精神病学讲师，对社会沟通有浓厚的兴趣。蒂莫西·罗伯茨博士和鲁本·古尔博士将指导他。Roberts博士是MEG和DTI技术的专家，研究重点是健康儿童和自闭症患者的听觉和语言处理的发展。Gur博士是神经心理学评估和神经影像学方面的专家，其研究涉及精神分裂症的情感和认知功能障碍。这些导师将确保从拟议的培训计划中获得的经验将使候选人能够建立一个独立的研究计划，该计划可以在社会沟通的发展神经科学方面做出重大贡献，并了解这种沟通功能障碍如何出现在精神分裂症和自闭症等神经精神疾病中。 公共卫生相关性：社会沟通障碍是神经精神疾病的一个持久和衰弱的方面。更好地了解这种功能障碍的神经本质以及它在发育过程中如何展开，应该提供重要的病因信息，可能导致新的治疗方法。这将有利于公共卫生，有助于促进病人融入社会。

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. PUBLIC HEALTH RELEVANCE: Impaired social communication is an enduring and debilitating aspect of neuropsychiatric illness. Greater understanding of the neural nature of this dysfunction and how it unfolds during development should provide important etiopathic information that could lead to new treatments. This would benefit public health by helping to facilitate patient integration into society.