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.

项目概要/摘要 背景：患有结节性硬化症 (TSC) 的儿童神经发育障碍的风险很高 其中，自闭症谱系障碍 (ASD) 的发病率接近 60%。前瞻性研究发现 患有 TSC 的婴儿在生命的第一年表现出社交沟通技能的延迟。然而，迄今为止还没有 研究调查了早期行为干预是否可以提高社交沟通技巧 患有 TSC 的婴儿。目标：该研究的总体目标是确定社交沟通是否 通过有针对性的短期行为干预，可以改善患有 TSC 的婴儿的功能 JASPER（共同注意力、象征性游戏、参与、调节），并丰富传统成果 通过将行为测量与社会的电生理（EEG）生物标志物相结合来进行测量 沟通。这些生物标志物可以捕捉大脑发育的微妙变化，这些变化可能反映 在明显的行为改变之前对治疗的反应，特别是对于患有明显行为改变的儿童 延迟发育，并且它们可以告知所发现的行为变化背后的神经机制 与干预。假设：预计与等待名单对照组相比，接受治疗的婴儿 JASPER 干预将在社交沟通技巧方面展现出更大的进步，同时捕捉到变化 行为学和电生理学。方法：总共 60 名 12-36 个月患有 TSC 的婴儿将接受 通过与 TSC 研究、加州大学洛杉矶分校和波士顿儿童医院建立合作关系，在两个地点进行招募 医院将每个婴儿随机分为治疗组或候补名单对照组。等候名单控制设计允许 所有婴儿接受干预，同时仍保留非治疗对照组。治疗将 包括为期 12 周的每周干预课程。评估（临床、行为和脑电图）将 治疗前、治疗后、完成后3个月、完成后12个月进行。 对照组将在同一时间点接受评估，然后在第 6 个月开始干预。 评估将包括社会沟通技能、认知、语言和能力的行为测量 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测量。影响：早期 干预可改善自闭症谱系障碍 (ASD) 的认知和行为结果，但尚无研究调查其效果 对患有 TSC 的婴儿进行有针对性的早期行为干预。早期干预效果的证据将 证明其对所有患有 TSC 的婴儿的价值，改善发育结果并减轻症状 导致 TSC 神经发育障碍的诊断。此外，这项研究具有相关性 通过脑电图生物标志物与神经发育障碍的整合进行干预研究 行为测量，因为这种方法可以更容易地捕捉语言前治疗的效果 以及发育迟缓的婴儿。