Medication-Induced Changes in Brain Function in Children with Tourette Syndrome

描述(由申请人提供)： 多发性抽动症(TS)是一种常见的遗传性神经系统疾病，始于儿童时期，表现为无法长期保持重复的、刻板印象的声音和动作(即语音和运动抽搐)。这项研究的目的是使用行为和神经成像工具来分析TS儿童的脑网络功能。重点是大脑中的区域功能相互作用，以及各个区域内的活动水平，以及标准TS药物治疗后它们可能会如何改变，如神经镇静剂和中枢作用的肾上腺素能药物。尽管我们知道这些治疗剂的药理特性，但我们不知道它们如何影响TS患者的脑功能。我们以前的工作(Church等人，2009，Brain；Baym等人)。2008年，Brain)提出，TS损害了大脑的任务控制网络，特别是影响到参与自适应控制的区域。这项建议研究了TS药物是否改善了这些适应性控制区以及被认为在TS中起作用的额叶和皮质下区域的活动情况。这项拟议的研究将采用重复测量设计，收集TS儿童在服药前和服药期间、休息期间和执行规则转换任务期间的脑部扫描。未受影响的儿童和未服用药物的TS儿童的对照组将在相同的时间间隔内进行扫描。TS组用药后区域或网络的变化可能揭示药物在大脑中的哪个部位具有最大的功能影响。我们还可以衡量患有TS的儿童在服药后的大脑活动是否看起来更类似于年龄匹配的健康儿童，或者是否有证据表明替代网络的补偿激活。这项研究向解决发育障碍研究面临的一些困难迈出了第一步(例如，症状严重程度、药物使用和与年龄相关的变化)。对于患有TS的儿童，建议的多方面治疗方法应该同时告知我们对这种疾病的理解以及常见TS治疗对大脑的影响。这项神经影像和行为研究应该有助于理清TS本身的影响，以及TS药物治疗对大脑功能的影响。如果成功，这项拟议研究的经验教训将对理解其他儿科神经精神障碍及其治疗产生影响。 公共卫生相关性： 这项神经影像和行为研究应该有助于理清TS本身的影响，以及TS药物治疗对大脑功能的影响。如果成功，这项拟议研究的经验教训将对理解其他儿科神经精神障碍及其治疗产生影响。

DESCRIPTION (provided by applicant): Tourette Syndrome (TS) is a common genetic neurological disease that begins in childhood, and is manifest as the inability to keep from making repetitive, stereotyped sounds and movements (i.e., phonic and motor tics) over long periods of time. The objective of this research is to use behavior and neuroimaging tools to analyze functional brain networks in children with TS. The focus is on regional functional interactions in the brain, as well as the activity level within individual regions, and how they may be altered after treatment with standard TS medications, such as neuroleptics and centrally acting adrenergic agents. Despite knowledge of the pharmacologic properties of these therapeutic agents, we do not know how they affect brain functioning in TS. Our previous work (Church et al., 2009, Brain; Baym et al. 2008, Brain) has suggested that TS impairs task control networks of the brain, particularly affecting regions involved in adaptive control. This proposal examines whether TS medication improves the profile of activity in these adaptive control regions, as well as in the frontal and subcortical regions thought to play a role in TS. The proposed study will utilize a repeated measures design, collecting brain scans of children with TS prior to and during medication use, during rest, and during performance of a rule-switching task. Control groups of unaffected children and unmedicated children with TS will be scanned over the same time interval. Regional or network changes after medication use in the TS group may reveal where in the brain the medications are having the greatest functional influence. We can also gauge whether the brain activity in children with TS post- medication looks more similar to that of healthy age-matched children or whether there is evidence of compensatory activation of an alternative network. This study takes a first step towards addressing some of the difficulties facing studies of developmental disorders (e.g. symptom severity, medication use, and age-related changes). The proposed multifaceted approach in children with TS should inform both our understanding of the disorder and the influence of common TS treatments on the brain. This neuroimaging and behavioral study should help to disentangle the effects of TS, per se, versus the effects of pharmacotherapy for TS, on brain functioning. If successful, the lessons from the proposed study will have implications for understanding other pediatric neuropsychiatric disorders and their treatments. PUBLIC HEALTH RELEVANCE: This neuroimaging and behavioral study should help to disentangle the effects of TS, per se, versus the effects of pharmacotherapy for TS, on brain functioning. If successful, the lessons from the proposed study will have implications for understanding other pediatric neuropsychiatric disorders and their treatments.