Multimodal Neuroimaging of Prosody in Schizophrenia and Developmental Disorders

描述（由申请人提供）：对于患有精神分裂症和自闭症等各种神经精神疾病的患者来说，无法通过声音调制（韵律）表达情感是社交认知功能障碍的一个主要方面。这些缺陷的神经机制，以及它们从童年到成年的发展过程，受到的研究关注却非常少。该培训计划旨在帮助候选人为解决这两个问题的独立研究做好准备。就韵律的神经机制而言，有一些证据表明韵律功能障碍与颞叶皮层和额叶皮层之间相互作用的破坏有关。该电路的时间部分似乎解析声音信号以进行情感区分，随后由额叶部分评估情感意义。该回路很可能介导精神分裂症的韵律功能障碍，这与基本的听觉感觉缺陷和异常的颞额叶相互作用有关。这里提出的研究将采用多模式神经影像方法，通过整合三种最先进的神经影像技术，对健康成人和精神分裂症患者的颞额叶回路进行首次全面描述。首先，脑磁图（MEG）与磁共振功能连接分析（fMRI）相结合，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完整性缺陷是精神分裂症韵律处理过程中异常颞额叶相互作用的基础。除了对候选人进行多模式神经影像培训外，拟议的活动还将为他提供语言发展心理学和听觉神经生物学的背景，以及为儿童和青少年开发和调整韵律任务的框架。该候选人是宾夕法尼亚大学精神病学讲师，对社交沟通有着浓厚的兴趣。博士。蒂莫西·罗伯茨和鲁本·古尔将指导他。 Roberts 博士是 MEG 和 DTI 技术方面的专家，其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。古尔博士是神经心理学评估和神经影像学专家，其研究涉及精神分裂症的情绪和认知功能障碍。这些导师将确保候选人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项目，该项目可以在社会沟通的发展神经科学方面做出重大贡献，并了解精神分裂症和自闭症等神经精神疾病中如何出现这种沟通功能障碍。 公共卫生相关性：社交沟通受损是神经精神疾病的一个持久且令人衰弱的方面。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，从而可能导致新的治疗方法。这将有助于促进患者融入社会，从而有益于公共健康。

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.