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

药物引起的抽动秽语综合征儿童脑功能变化

• 批准号: 8063600
• 负责人: Jessica Alice Church-Lang
• 金额: $ 5.3万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063600
• 关键词: Address; Adolescent; Adrenergic Agents; Affect; Aftercare; Age; Antipsychotic Agents; Basal Ganglia; Behavior; Behavioral; Biological Markers; Brain; Brain region; Brain scan; Child; Childhood; Chronic; Clinical; Control Groups; Corpus striatum structure; Development; Disease; Early Diagnosis; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Genetic; Gilles de la Tourette syndrome; Goals; Hydrocortisone; Individual; Individual Differences; Knowledge; Measures; Mentors; Motor Tics; Movement; Participant; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Physicians; Play; Process; Property; Psychometrics; Reaction Time; Recording of previous events; Regulation; Research; Rest; Role; Scanning; Severities; Stereotyping; Stressful Event; Structure; Symptoms; System; Techniques; Testing; Therapeutic Agents; Time; Vocal Tics; Work; age related; cognitive function; design; developmental disease; effective therapy; executive function; experience; frontal lobe; improved; nervous system disorder; neuroimaging; neuropsychiatry; public health relevance; sound; time interval; tool

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.

描述（由申请人提供）： 图雷特综合征（TS）是一种常见的遗传性神经疾病，始于儿童时期，表现为无法避免发出重复的、刻板的声音和动作（即，语音和运动抽搐）。本研究的目的是使用行为和神经影像学工具来分析TS儿童的脑功能网络。重点是在大脑中的区域功能的相互作用，以及在个别区域内的活动水平，以及如何与标准的TS药物，如抗精神病药和中枢作用肾上腺素能药物治疗后，他们可能会改变。尽管这些治疗药物的药理学特性的知识，我们不知道他们如何影响脑功能的TS。我们以前的工作（Church等人，2009年，《大脑》; Baym等人，2008年，Brain）已经表明TS损害大脑的任务控制网络，特别是影响涉及适应性控制的区域。该建议检查TS药物是否改善了这些自适应控制区域以及被认为在TS中发挥作用的额叶和皮质下区域的活动概况。 拟议的研究将采用重复测量设计，收集TS儿童在用药前和用药期间、休息期间和执行规则转换任务期间的脑部扫描。对照组未受影响的儿童和未用药的TS儿童将在相同的时间间隔内进行扫描。TS组中药物使用后的区域或网络变化可能揭示药物在大脑中具有最大的功能影响。我们还可以评估TS儿童的大脑活动是否与健康年龄匹配的儿童更相似，或者是否有替代网络代偿激活的证据。这项研究迈出了解决发育障碍研究面临的一些困难的第一步（例如症状严重程度，药物使用和年龄相关的变化）。在TS儿童中提出的多方面方法应该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。 这项神经影像学和行为学研究应该有助于理清TS本身对大脑功能的影响，以及药物治疗对TS的影响。如果成功的话，从拟议的研究中获得的经验教训将对理解其他儿科神经精神疾病及其治疗产生影响。 公共卫生相关性： 这项神经影像学和行为学研究应该有助于理清TS本身对大脑功能的影响，以及药物治疗对TS的影响。如果成功的话，从拟议的研究中获得的经验教训将对理解其他儿科神经精神疾病及其治疗产生影响。