Mechanisms of change with early intervention in Tuberous Sclerosis Complex

结节性硬化症早期干预的变化机制

• 批准号: 9921443
• 负责人: Shafali Spurling Jeste
• 金额: $ 51.87万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9921443
• 关键词: Address; Affect; Aftercare; Age; Attenuated; Behavior; Behavior Therapy; Behavioral; Biological Markers; Boston; Brain; Caring; Child; Clinical; Clinical Trials; Cognition; Cognitive; Collaborations; Control Groups; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Early Intervention; Early identification; Electrophysiology (science); Enrollment; Event; Face; Face Processing; Genetic; Genetic Diseases; Goals; Growth; Infant; Intellectual functioning disability; Interdisciplinary Study; Intervention; Intervention Studies; Joints; Language; Lead; Life; Maintenance; Measures; Mediating; Methodology; Mission; Modification; National Institute of Child Health and Human Development; Neurodevelopmental Disability; Neurodevelopmental Disorder; Non-Malignant; Outcome; Outcome Measure; Parents; Pediatric Hospitals; Play; Prenatal Diagnosis; Process; Prospective Studies; Randomized; Regulation; Research; Rest; Site; Social Development; Symptoms; Syndrome; Time; Translational Research; Tuberous sclerosis protein complex; Waiting Lists; autism spectrum disorder; autistic children; behavior change; behavior measurement; behavioral outcome; body system; cognitive neuroscience; comparison group; design; group intervention; high risk; improved; intervention effect; joint attention; neuromechanism; prevent; recruit; relating to nervous system; response; skills; social communication; specific biomarkers; treatment effect; treatment response; visual processing

PROJECT SUMMARY/ABSTRACT Background: Children with Tuberous Sclerosis Complex (TSC) are at high risk for neurodevelopmental disorders, with rates of autism spectrum disorder (ASD) approaching 60%. Prospective studies have found that infants with TSC demonstrate delays in social communication skills in the first year of life. However, to date no studies have investigated whether early behavioral intervention can improve social communication skills in infants with TSC. Objectives: The overarching goal of the study is to determine if social communication function can be improved in infants with TSC with a targeted, short-term behavioral intervention called JASPER (Joint Attention, Symbolic Play, Engagement, Regulation), and to enrich traditional outcome measures by combining behavioral measures with electrophysiological (EEG) biomarkers of social communication. These biomarkers can capture subtle changes in brain development that may reflect responses to treatment prior to an overt behavioral change, particularly relevant for children with significantly delayed development, and they can inform the neural mechanisms underlying the behavioral changes found with intervention. Hypothesis: It is expected that, compared to a wait list control group, infants receiving the JASPER intervention will demonstrate greater gains in social communication skills, with changes captured both behaviorally and electrophysiologically. Methodology: A total of 60 infants with TSC ages 12-36 months will be recruited across two sites with an established collaboration in TSC research, UCLA and Boston Children's Hospital, with each infant randomized to treatment or wait list control group. The wait list control design allows all infants to receive intervention while still maintaining a non-treatment comparison group. Treatment will consist of 12 weeks of weekly intervention sessions. Assessments (clinical, behavioral and EEG) will be performed before treatment, after treatment, 3 months after completion, and then 12 months after completion. Controls will undergo assessments at the same time points, and then will start intervention at month 6. Assessments will include behavioral measures of social communication skills, cognition, language and adaptive function, and EEG measure of resting state brain activity, visual and face processing. Impact: Early intervention improves cognitive and behavioral outcomes in ASD, yet no studies have investigated the effects of targeted, early behavioral intervention in infants with TSC. Evidence of efficacy of early intervention will justify its value for all infants with TSC, improving developmental outcomes and attenuating symptoms that lead to the diagnosis of neurodevelopmental disabilities in TSC. Moreover, this study holds relevance for intervention research across neurodevelopmental disorders through its integration of EEG biomarkers with behavioral measures, as such methodology may more readily capture the effects of treatment in pre-verbal and developmentally delayed infants.

项目摘要/摘要 背景：结节性硬化症复合物（TSC）的儿童有神经发育的高风险 疾病，自闭症谱系障碍（ASD）的率接近60％。前瞻性研究发现 患有TSC的婴儿表明，在生命的第一年，社会沟通技巧的延迟。但是，迄今为止否 研究已经调查了早期行为干预是否可以提高社会沟通能力 患有TSC的婴儿。目标：研究的总体目标是确定社会交流是否 具有针对性的短期行为干预措施的TSC婴儿可以改善功能 jasper（共同关注，象征性游戏，参与，监管），并丰富传统结果 通过将行为度量与社会生物学（EEG）生物标志物结合起来的措施 沟通。这些生物标志物可以捕获大脑发育的细微变化，这可能反映 明显的行为改变之前对治疗的反应，尤其是与患有明显的儿童有关 延迟发展，他们可以告知所发现行为变化的神经机制 干预。假设：预计，与等待列表对照组相比，婴儿接受了 贾斯珀干预将证明社交沟通技巧的提高，并捕获了变化 行为和电生理学。方法论：总共有60名TSC年龄12-36个月的婴儿将 可以在TSC Research，UCLA和波士顿儿童的两个网站上招募两个网站 医院，每个婴儿随机进行治疗或等待列表对照组。等待列表控制设计允许 所有婴儿都接受干预措施，同时仍保持非治疗比较组。治疗将 包括12周的每周干预课程。评估（临床，行为和脑电图）将是 在治疗之前，完成后，完成3个月以及完成后12个月进行治疗。 控件将在同一时间点进行评估，然后在第6个月开始干预。 评估将包括社会沟通技巧，认知，语言和语言和 自适应功能以及静息状态大脑活动，视觉和面部处理的脑电图。影响：早期 干预措施改善了ASD的认知和行为结果，但是没有研究研究这些影响 TSC婴儿的靶向早期行为干预。早期干预功效的证据将 证明其对所有TSC婴儿的价值合理，改善了发育效果并减轻症状 导致TSC中神经发育障碍的诊断。而且，这项研究与 通过将脑电图生物标志物的整合与神经发育障碍的干预研究 行为措施，因为这种方法可能会更容易捕获治疗在言语中的影响 并发育延迟的婴儿。