Longitudinal Study of Brain Imaging and Cognitive Markers of Tourette Syndrome in Children

儿童抽动秽语综合征脑影像和认知标志物的纵向研究

• 批准号: 10220354
• 负责人: Deanna Jacquelyn Greene
• 金额: $ 55.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220354
• 关键词: 12 year old; 7 year old; Adolescence; Adult; Age; Brain; Brain imaging; Child; Chronic; Classification; Clinical; Clinical Data; Cognitive; Complex; Data; Data Set; Development; Diagnosis; Diagnostic; Future; Gilles de la Tourette syndrome; Impairment; Individual; Intervention; Investigation; Life; Literature; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Measures; Mediating; Methods; Modeling; Motor; Motor Tics; Movement; Neurobiology; Neurodevelopmental Disorder; Noise; Outcome; Patients; Pattern; Prognosis; Public Health; Quality of life; Research; Rest; Severities; Site; Structure; Symptoms; Testing; Thalamic structure; Tic disorder; Time; Treatment Protocols; United States National Institutes of Health; Universities; Validation; Vocal Tics; Washington; aggressive therapy; base; brain volume; caudate nucleus; cognitive ability; cognitive control; cognitive function; epidemiologic data; epidemiology study; experience; gray matter; improved; insight; longitudinal design; machine learning method; mind control; multidimensional data; multimodal data; multimodality; novel; predict clinical outcome; putamen; symptomatic improvement; white matter

PROJECT SUMMARY/ABSTRACT Chronic tic disorders (referred to here as Tourette syndrome: TS) are complex and often serious neurodevelopmental disorders characterized by motor and/or vocal tics. Tics are brief, repetitive, unwanted movements or noises, which can severely impinge upon quality of life. While TS was once thought to be relatively rare, recent epidemiological studies find that 1-6% of all children meet criteria for a chronic tic disorder, making it a significant public health problem. Typically in TS, tics begin around age 5-7 years old, peak in severity around age 10-12 years, and improve throughout adolescence into adulthood. However, not all patients show this improvement during adolescence, as ~30% continue to experience significant impairment into adulthood. Thus, the years during and immediately following peak symptom severity represent a critical time for TS, during which individuals may show considerable improvement or not. Surprisingly little research has targeted this critical developmental stage of TS. Moreover, longitudinal investigations of predictors of TS outcome have focused primarily on single variables (e.g., caudate nucleus volume or tic severity). Yet there is considerable evidence that the neurobiology of TS is quite complex, involving interactions within and between multiple brain networks. For example, our preliminary findings demonstrate stronger brain functional connectivity among cognitive control networks and motor networks, as well as altered white and gray matter volumes in prefrontal and subcortical regions in TS. Using this complex information may be more informative for understanding tic severity changes and predicting clinical outcome. We propose a longitudinal study in which we will capture the developmental stage of TS with the greatest likelihood of change in tic severity (beginning at age 10-12 years), and will follow these children to track the development of brain and cognitive features, and how they relate to symptom change, over time. To capture the complex neurobiology of TS, we will collect whole-brain resting state functional connectivity, structural MRI, cognitive, and clinical data from a group of children with TS. We will compare these children to tic-free controls (from the NIH's ABCD Study Washington University site subject pool), as comparison to typical development will be essential for interpreting longitudinal changes in TS. We will target diagnostic differences and developmental changes in specific functional brain networks, regional brain volumes, and cognitive abilities. We will also use multivariate machine learning methods to unify this rich dataset to classify and make predictions about individual children. This approach analyzes complex patterns of multidimensional data rather than single variables, providing the potential for clinical utility and to contribute converging evidence about mechanism. Identifying mechanisms underlying symptom change will provide insight into why many children with TS improve while some do not, potentially yielding new targets for treatment and predictive indicators of persistent tics. Markers of symptom improvement could be targeted to treat children who do not improve. Being able to make predictions about individual children could identify those children who need those interventions most. We have expertise with every step of the proposed study, but the application to longitudinal data over the first half of the second decade of life is novel.

项目总结/摘要 慢性抽动障碍（这里称为抽动秽语综合征：TS）是一种复杂的，往往是严重的神经发育障碍， 以运动和/或发声抽搐为特征的疾病。抽搐是短暂的，重复的，不必要的运动或噪音， 严重影响生活质量。虽然TS曾经被认为是相对罕见的，但最近的流行病学研究发现， 1-6%的儿童符合慢性抽动障碍的标准，使其成为一个重要的公共卫生问题。通常在 TS，抽搐开始于5-7岁左右，严重程度在10-12岁左右达到高峰，并在整个青春期得到改善 长大成人然而，并非所有患者在青春期都表现出这种改善，因为约30%的患者继续经历 成年后的严重损害。因此，在症状严重程度高峰期间和紧随其后的几年里， 代表TS的关键时刻，在此期间，个人可能会表现出相当大的改善或没有。少得惊人 研究已经瞄准了TS的这个关键发展阶段。此外，TS预测因子的纵向研究 结果主要集中在单个变量上（例如，尾状核体积或抽搐严重程度）。然而有 有相当多的证据表明，TS的神经生物学是相当复杂的，涉及多个神经元内和多个神经元之间的相互作用。 大脑网络例如，我们的初步研究结果表明， 认知控制网络和运动网络，以及改变白色和灰质体积在前额叶和 TS的皮质下区域。使用这些复杂的信息可能对了解抽搐的严重程度更有帮助 变化和预测临床结果。 我们提出了一项纵向研究，在这项研究中，我们将捕捉TS的发展阶段， 抽搐严重程度的变化（从10-12岁开始），并将跟踪这些儿童的大脑发育， 认知特征，以及它们与症状变化的关系。为了捕捉TS的复杂神经生物学，我们 将收集全脑静息状态功能连接，结构MRI，认知和临床数据，从一组 儿童TS我们将这些儿童与无抽搐的对照组进行比较（来自NIH的ABCD研究华盛顿 大学网站主题库），因为与典型发展的比较对于解释纵向变化至关重要 在TS。我们将针对特定功能脑网络的诊断差异和发育变化，区域 脑容量和认知能力。我们还将使用多变量机器学习方法来统一这个丰富的数据集， 对每个孩子进行分类和预测。这种方法分析了多维的复杂模式， 数据而不是单一变量，提供了临床实用性的潜力，并提供了关于以下方面的汇聚证据： 机制确定症状变化的潜在机制将有助于深入了解为什么许多患有TS的儿童 改善，而有些没有，可能产生新的治疗目标和持续性抽搐的预测指标。 症状改善的标志物可以有针对性地治疗没有改善的儿童。能够做出预测 可以确定哪些儿童最需要这些干预措施。我们拥有专业知识， 这是拟议研究的第一步，但对生命第二个十年前半期纵向数据的应用是新颖的。