Multimodal assessment of sensory processing dysfunction in schizophrenia

精神分裂症感觉处理功能障碍的多模式评估

• 批准号: 8105219
• 负责人: DANIEL C. JAVITT
• 金额: $ 21.34万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8105219
• 关键词: Affect; Animals; Attention; Attentional deficit; Behavior; Chronic Schizophrenia; Cognitive; Collaborations; Coupling; Diagnosis; Early Diagnosis; Etiology; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Generations; High Frequency Oscillation; Impaired cognition; Impairment; Instruction; Intervention; Lead; Location; Measures; Mental disorders; Methods; Modeling; Multimodal Imaging; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neurocognitive; Neurons; Outcome; Patients; Phase; Process; Relative (related person); Rest; Role; Schizophrenia; Sensory; Sensory Process; Signal Transduction; Stimulus; Testing; Visual; Visual evoked cortical potential; attentional modulation; base; improved; magnocellular; neurophysiology; prevent; programs; research study; response; sample fixation; transmission process; visual process; visual processing; volunteer

Sensory processing deficits are a key component of schizophrenia. This project will analyze mechanisms underlying sensory processing dysfunction using a multimodal imaging approach incorporating both neurophysiological and MRl-based assessments. Neurophysiological studies will evaluate role of neuronal synchrony and oscillatory hierarchy impairments in etiology of neurocognitive dysfunction. In particular, it will test the hypothesis that impairments in non-linear stimulus amplification and in oscillatory entrainment may prevent response optimization in patients relative to controls. Four experiments are planned. The first experiment will analyze the role of oscillatory entrainment in the genesis of previously documented sensory processing deficits and object-attention dysfunction. For this experiment, hierarchical oscillatory analyses will be conducted using mathematical approaches and stimulation paradigms developed from Projects 2 and 3, respectively. The second experiment will analyze the role of spatial attention in sensory processing dysfunction, also using both standard ERP and oscillatory hierarchy analyses, and will also evaluate the role of phase reset vs. exogenous activity in ERP generation in patients and controls. Experiment 3 will evaluate spatial attention effects further using ssVEP approaches. Deficits in ERP generation will also be assessed relative to symptomatic and cognitive measures. The fourth experiment will evaluate the role of structural and functional connectivity impairments in etiology of sensory and attentional deficits using MR measures supported by Core B. DTI measures will be used to assess structural connectivity, while resting state fMRI will be used to assess functional connectivity. An underiying hypothesis is that deficits in neurophysiological processes such as non¿ linear gain and slow oscillatory function that are known to be NMDA receptor-dependent will lead to impaired entrainment of higher-frequency oscillations (e.g. delta, theta, gamma), leading to impaired ERP generation and behavior. Overall, this project will test the hypothesis that deficits in hierarchical processing within regions and structural and functional connectivity between regions lead to deficits in neurocognitive function in schizophrenia. RELEVANCE (See instructions): Schizophrenia is a major mental disorder. Neurocognitive dysfunction is a core component of schizophrenia and a major determinant of poor long-term outcome. This project will evaluate mechanisms underlying deficits in sensory processing and neurocognitive dysfunction in patients with chronic schizophrenia, in collaboration with other projects and core programs in order to develop improved methods for early detection, diagnosis and intervention.

感觉处理缺陷是精神分裂症的关键组成部分。这个项目将分析 使用多模式成像方法的感觉处理功能障碍的机制 纳入神经生理学和基于MRL的评估。神经生理学研究 将评估神经元同步和振荡性层次结构在病因中的作用 神经认知功能障碍。特别是，它将检验非线性损害的假设 刺激放大和振荡性的灌落可能会阻止患者的反应优化 相对于控件。计划了四个实验。第一个实验将分析 先前记录的感官处理缺陷的起源中的振荡性。 对象注意功能障碍。对于此实验，将进行层次振荡分析 使用从项目2和3开发的数学方法和刺激范例， 分别。第二个实验将分析空间注意力在感觉处理中的作用 功能障碍，也使用标准ERP和振荡性层次结构分析，也将 评估患者和对照组中ERP产生中相位重置与外源活性的作用。 实验3将使用SSVEP方法进一步评估空间注意力效应。缺陷 相对于有症状和认知措施，还将评估ERP的产生。第四 实验将评估结构和功能连通性障碍在病因中的作用 使用由Core B. DTI测量支持的MR测量值的感觉和注意力缺陷将是 用于评估结构连通性，而静止状态fMRI将用于评估功能 连接性。一个基本的假设是在神经生理过程（例如非nonâ）中的防御能力 线性增益和缓慢的振荡功能已知NMDA接收器依赖性将导致 高频振荡的入口受损（例如Delta，Theta，Gamma），导致 ERP的产生和行为受损。总体而言，该项目将检验定义的假设 区域内的分层处理以及区域之间的结构和功能连接 导致精神分裂症的神经认知功能定义。 相关性（请参阅说明）： 精神分裂症是一种主要的精神障碍。神经认知功能障碍是 精神分裂症和长期结局差的主要决定因素。这个项目将评估 患者的感觉处理和神经认知功能障碍的缺乏的机制 与慢性精神分裂症一起，与其他项目和核心计划合作，以便 开发改进的方法来提早检测，诊断和干预。