Understanding neurophysiological deficits in response inhibition in children with FASD

了解 FASD 儿童反应抑制的神经生理学缺陷

• 批准号: 10207337
• 负责人: JULIA MARIE STEPHEN
• 金额: $ 20.68万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207337
• 关键词: Accounting; Achievement; Adult; Age; Age-Years; Anterior; Attention; Autonomic nervous system; Behavioral; Brain; Brain region; Child; Clinical; Diagnosis; Disease; Early Intervention; Early identification; Early treatment; Electroencephalography; Ethanol; Event; Face; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Functional Magnetic Resonance Imaging; Goals; Grant; Impairment; Imprisonment; Impulsive Behavior; Individual; Intervention; Lead; Link; Literature; Location; Long-Term Effects; Maps; Measurable; Measures; Mediating; Modeling; Motivation; Mus; Neurocognitive; Neurocognitive Deficit; Occupational; Outcome; Parietal; Parietal Lobe; Pattern; Performance; Pharmacology; Play; Population; Predisposition; Prefrontal Cortex; Prevalence; Quality of life; Rattus; Resolution; Rest; Risk; Risk Factors; School-Age Population; Social Functioning; Source; Structure; Substance Use Disorder; Techniques; Transcranial magnetic stimulation; addiction; autism spectrum disorder; base; behavior measurement; cingulate cortex; cognitive control; cohort; developmental disease; executive function; experience; fetal; frontal lobe; heart rate variability; high risk; improved; neuroimaging; neurophysiology; neuropsychiatric disorder; outcome prediction; relating to nervous system; response; signal processing; sustained attention; temporal measurement; therapy development

Abstract Recognition of subtle signs of fetal alcohol spectrum disorder has increased the estimated prevalence rate to between 2-5% of school-aged children. While the neurocognitive profile of FASD has been characterized, the underlying mechanisms that lead to these neurocognitive deficits are still poorly understood. Poor inhibitory functioning is one of the executive function impairments identified in children with FASD and likely is related to many of the secondary deficits experienced by individuals with FASD including increased rates of addictions, incarceration and susceptibility to other neuropsychiatric disorders. Therefore, understanding the underlying brain mechanisms that lead to impaired inhibitory functioning in early elementary age children is important to guide development of intervention approaches. In other clinical populations altered functional network connectivity assessed with fMRI is associated with poor inhibitory functioning. Another large body of work originating largely from EEG indicates that neural oscillations play a key role in cognitive control and mediating inhibitory responses. By using MEG we will extend these prior EEG results to the FASD population through identifying the cortical source location and timing of evoked activity and examining resting network connectivity at the source level. Using the high temporal resolution of MEG, we will capture both resting neural oscillations, resting brain connectivity, and task evoked neural oscillations related to both successful and unsuccessful inhibition during a child-friendly Go/No-Go task. This project period will examine younger children in the 6-8 year age range and focus on neural oscillations using MEG and functional network connectivity using both MEG and fMRI. Aim 1 will use MEG to examine event-related responses, including averaged evoked response and task-evoked neural oscillations during the Go/No-Go task. This aim will, in part, replicate the averaged evoked response results obtained in the current project period in a younger independent cohort and will extend the prior project period aim by examining task-evoked neural oscillations allowing us to capture theta and beta oscillations related to cognitive control. Aim 2 will examine resting neural oscillations and resting functional network connectivity using both MEG and fMRI. Recent results indicate that resting functional network connectivity patterns differ by clinical disorders. Aim 3 will examine this question directly by linking the results from Aim 1 and Aim 2 as well as behavioral measures of inhibitory functioning in these children to determine what functional brain measures predict inhibitory functioning in children with FASD and healthy controls. Project 5 is complementary to each of the other projects in this center grant with neural oscillations in mouse and rat models examined in Projects 3&4. Furthermore, autonomic nervous system response will be assessed through heart rate variability in support of project 2. Combined, these projects will provide translational results to take measurable steps toward developing mechanistic-based interventions for children with FASD.

抽象的 认识到胎儿酒精谱系障碍的微妙迹象已将估计患病率提高到 介于2-5％的学龄儿童。虽然FASD的神经认知概况已被表征，但 导致这些神经认知缺陷的基本机制仍然很少了解。抑制性差 功能是FASD儿童发现的执行功能障碍之一，可能与 FASD个人遇到的许多次要缺陷，包括成瘾率提高， 对其他神经精神疾病的监禁和易感性。因此，了解基础 导致初级儿童抑制性功能受损的大脑机制对于 指导干预方法的发展。在其他临床人群中，功能网络改变了 通过fMRI评估的连通性与抑制功能差有关。另一个大型工作 源自脑电图的主要源自脑电图，表明神经振荡在认知控制和介导中起关键作用 抑制反应。通过使用MEG，我们将通过 确定诱发活动的皮质源位置和时间安排并检查静止网络连接 在源级别。使用MEG的高时间分辨率，我们将捕获两个静止的神经振荡， 静止的大脑连通性以及任务引起与成功和失败有关的神经振荡 在儿童友好的执行/禁止任务中的抑制。这个项目时期将检查6-8岁的小孩 使用MEG和功能网络连接的年龄范围，并专注于神经振荡 梅格和fMRI。 AIM 1将使用MEG检查与事件相关的响应，包括平均唤起响应 以及任务诱发的神经振荡在GO/NO-GO任务中。这个目标将部分复制平均 在当前项目期间在年轻的独立队列中获得的诱发响应结果，并将扩展 以前的项目时期通过检查任务引起的神经振荡，使我们能够捕获Theta和Beta 与认知控制有关的振荡。 AIM 2将检查静止的神经振荡和静止功能 使用MEG和fMRI的网络连接。最近的结果表明静止功能网络 连通性模式因临床疾病而有所不同。 AIM 3将通过链接结果直接检查这个问题 来自AIM 1和AIM 2以及这些儿童抑制功能的行为度量，以确定 哪些功能性大脑测量可以预测FASD和健康对照儿童的抑制作用。 项目5与该中心拨款中的其他项目相辅相成，并具有鼠标中的神经振荡 和项目3和4中检查的老鼠模型。此外，将评估自主神经系统的反应 通过支持项目2的心率变异性。结合在一起，这些项目将提供翻译结果 采取可衡量的步骤，为FASD儿童开发基于机械的干预措施。