IMAGING AND MODELING THERAPEUTIC MECHANISMS OF ACTION

治疗作用机制的成像和建模

• 批准号: 6480073
• 负责人: PETER Thornton FOX
• 金额: $ 17.69万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6480073
• 关键词: Parkinson's disease; bioimaging /biomedical imaging; brain electrical activity; brain imaging /visualization /scanning; brain mapping; cerebral cortex; clinical research; functional magnetic resonance imaging; human subject; image processing; interhemispheric transfer; neural information processing; neural plasticity; neuropsychology; phonology; positron emission tomography; sensorimotor system; speech disorders; speech therapy; transcranial magnetic stimulation; vocalization; voice

DESCRIPTION (provided by applicant): The long-range vision of the proposed research program is to develop imaging strategies to study mechanisms of action of therapeutic interventions in brain disorders. The immediate goal of this proposal is to study mechanisms of action of treatment in Idiopathic Parkinson's Disease (IPD). Mechanism of action is a fundamentally important research objective, as the rational development of new treatments demands an understanding of mechanisms of action. Mechanism of action is a timely direction for imaging research, because methods are emerging which can demonstrate changes in variables directly related to mechanism of action, namely: 1) task-performance strategy (measured as the set of brain functional areas recruited by the task); 2) information exchange (measured as inter-regional functional co-variance during performance); and 3) connectivity & synaptic weighting and plastic changes therein (measured as inter-regional functional covariance during rest). Further, Structural Equation Modeling (SEM) offers a modeling construct for merging these three types of measurement into a functional system model. Herein, we propose to study the mechanism of action of the Lee Silverman Voice Treatment (LSVT) for hypophonia in IPD. Image-data acquired will include: functional MRI at rest and during speech, H21 0 PET at rest, during speech and during image guided TMS to the SMA. Task-performance strategy will be assessed by functional activity during overt speech (paragraph reading) imaged with both H2O PET and with fMRI. Information exchange (inter-regional covariance during task) will be computed from each functional data set. Anatomical connectivity (interregional covariance during rest) will be measured with TMS/PET and with resting-state MRI. Structural Equation Modeling will be applied to PET- and fMR1-derived measures of strategy, information exchange and connectivity, to model the speech-motor system pre- and post-LSVT. All measures will be performed before and after 4 weeks of LSVT in 10 hypophonic IPD patients selected for LSVT. Once established, these methods have the potential to provide tools for exploring mechanism of action and thereby providing a rationale basis for the development of new treatments in IPD, as well as in many neurological, psychiatric and developmental disorders.

描述(由申请人提供)：建议的长远愿景 研究计划是开发成像策略来研究作用机制 脑部疾病的治疗干预。这样做的直接目标是 建议研究特发性疾病的治疗作用机制 帕金森氏病(IPD)。行动机制是一个根本性的重要 研究目标，由于新疗法的合理发展需要一个 对作用机制的理解。行动机制是一个及时的 成像研究的方向，因为正在出现的方法可以 展示与作用机制直接相关的变量的变化， 即：1)任务绩效策略(以脑功能集合来衡量 任务招募的领域)；2)信息交流(以 业绩期间的区域间职能协方差)；3)连通性 &突触权重和其中的可塑性变化(以区域间衡量 休息期间的功能协方差)。进一步，结构方程建模(SEM) 提供了一个建模构造，用于将这三种类型的度量合并到 功能系统模型。在此，我们建议研究其作用机制。 Lee Silverman语音疗法(LSVT)治疗IPD发音障碍图像数据 获得者将包括：休息和说话时的功能磁共振，H21 0PET 休息，在讲话期间和在图像引导下对SMA进行TMS。任务绩效 策略将根据公开演讲期间的功能活动进行评估(第 阅读)同时使用H2O PET和fMRI进行成像。信息交流 (任务期间的区域间协方差)将从每个职能部门计算 数据集。解剖连通性(REST期间的区域间协方差)将 分别用TMS/PET和静息MRI进行测量。结构方程 建模将应用于PET和FMR1导出的战略措施， 信息交换和连接，为语音-运动系统预建模 和LSVT后。所有测量将在LSVT前和后4周进行 选择10例低音型IPD患者行LSVT。一旦建立起来，这些 方法有可能为探索作用机制提供工具 从而为新疗法的开发提供了理论基础 在IPD以及许多神经学、精神病学和发育学领域 精神错乱。