LONGITUDINAL EFFECTS OF TREATMENT ON BRAIN FUNCTION IN CHILDREN WITH TOURETTE SYN

描述(申请人提供)：多发性抽动症(TS)是一种常见的遗传性儿科神经精神障碍。表现为慢性运动和声带痉挛，影响大约0.3%-1%的儿童，对生活质量有显著的负面影响。TS与冲动调节和执行控制功能的缺陷有关。大脑的执行控制系统被认为在解剖学上与下游的瞬间处理系统是分开的，并由功能不同的区域网络组成。这些控制系统与处理系统的相互作用在TS中有牵连。这一探索性建议背后的一个关键思想是，TS源于控制区网络及其相互作用的非典型发展，而不是任何特定大脑区域的非典型功能。缓解TS抽搐的药物也可能导致控制能力的改善，以及控制区内的诱发活动和组成控制网络的区域之间的功能连接的正常化。我们假设，在TS中观察到的大脑激活和功能连接的异常模式将通过治疗TS的药物来改善。了解大脑的控制网络会受到药物的影响，可能会为TS和其他儿童神经精神障碍的早期诊断和更有效的治疗奠定基础。 公共卫生相关性：这项建议旨在使用纵向基于任务的功能磁共振成像和功能连接磁共振成像来表征儿童抽动秽语综合征控制网络的发展以及这些网络对药物治疗干预的反应。了解抽动症患者药物治疗对参与控制的脑区网络的影响，可能为早期诊断、更准确的预后和更有效的治疗奠定基础。

DESCRIPTION (provided by applicant): Tourette Syndrome (TS) is a common genetic pediatric neuropsychiatric disorder. Manifest as chronic motor and vocal tics, it affects approximately 0.3-1% of children, with significant negative impact on quality of life. TS is associated with deficits in impulse regulation and executive control functions. The brain's executive control systems are thought to be anatomically separate from downstream moment-to-moment processing systems and to consist of networks of functionally diverse regions. The interactions of these control systems with processing systems have been implicated in TS. A key idea underlying this exploratory proposal is that TS arises from the atypical development of networks of control regions and their interactions, as opposed to the atypical functioning of any particular brain region. Medications that relieve tics in TS may also result in an improvement in control abilities, and a normalization of both evoked activity within control regions and of functional connectivity between regions comprising control networks. We hypothesis that the anomalous patterns of brain activation and functional connectivity observed in TS will be ameliorated by medications that treat TS. Understanding the brain's control networks are affected by medications may lay the foundation for earlier diagnosis and more effective therapies for TS and other pediatric neuropsychiatric disorders. PUBLIC HEALTH RELEVANCE: This proposal aims to use longitudinal task-based fMRI and functional connectivity MRI to characterize the development of control networks in pediatric Tourette Syndrome and how those networks respond to pharmacotherapeutic intervention. Understanding how networks of brain regions involved in control are affected by pharmacotherapy in patient with Tourette Syndrome may lay the foundation for earlier diagnosis, more accurate prognosis, and more effective therapies