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

基本信息

批准号：
10674497
负责人：
JULIA MARIE STEPHEN
金额：
$ 18.57万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
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/10674497
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 Friends Functional Magnetic Resonance Imaging Goals Grant Impairment Imprisonment Impulsive Behavior Individual Intervention Link Literature Location Long-Term Effects Maps Measurable Measures Mediating Modeling Motivation Mus Neurocognitive Neurocognitive Deficit Occupational Outcome Parietal Parietal Lobe Pattern Performance Play Population Predisposition Prefrontal Cortex Prevalence Quality of life Rattus Resolution Rest Risk Risk Factors School-Age Population Social Functioning Source Substance Use Disorder Techniques Transcranial magnetic stimulation addiction autism spectrum disorder behavior measurement cingulate cortex cognitive control cohort developmental disease examination questions executive function experience fetal frontal lobe heart rate variability high risk improved neural neuroimaging neurophysiology neuropsychiatric disorder outcome prediction pharmacologic response signal processing sustained attention temporal measurement therapy development transcranial direct current stimulation

项目摘要

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.

抽象的对胎儿酒精谱系障碍的微妙迹象的认识已将估计患病率提高到学龄儿童的 2-5%。虽然 FASD 的神经认知特征已得到表征，导致这些神经认知缺陷的潜在机制仍然知之甚少。抑制性差功能障碍是 FASD 儿童的执行功能障碍之一，可能与以下因素有关： FASD 患者经历的许多继发性缺陷包括成瘾率增加，监禁和对其他神经精神疾病的易感性。因此，了解底层导致小学早期儿童抑制功能受损的大脑机制对于指导干预方法的制定。在其他临床人群中功能网络发生改变通过功能磁共振成像评估的连接性与抑制功能较差有关。又一大批作品主要源自脑电图表明神经振荡在认知控制和调解中发挥着关键作用抑制反应。通过使用 MEG，我们将通过以下方式将这些先前的 EEG 结果扩展到 FASD 人群：识别皮质源位置和诱发活动的时间并检查静息网络连接在源级别。利用 MEG 的高时间分辨率，我们将捕获静息神经振荡，静息时的大脑连接以及任务引起的与成功和不成功相关的神经振荡在儿童友好的“进行/不进行”任务中进行抑制。该项目期间将检查 6-8 岁的幼儿年龄范围，并重点关注使用 MEG 的神经振荡和使用两者的功能网络连接脑磁图和功能磁共振成像。目标 1 将使用 MEG 检查事件相关反应，包括平均诱发反应以及执行/不执行任务期间任务诱发的神经振荡。这一目标将在一定程度上复制平均水平在当前项目期间在较年轻的独立队列中获得的诱发反应结果，并将延长之前的项目期间的目标是检查任务诱发的神经振荡，使我们能够捕获 theta 和 beta 与认知控制相关的振荡。目标 2 将检查静息神经振荡和静息功能使用 MEG 和 fMRI 进行网络连接。最近的结果表明，静息功能网络连接模式因临床疾病而异。目标 3 将通过链接结果直接检验该问题根据目标 1 和目标 2 以及这些儿童的抑制功能的行为测量来确定哪些功能性大脑测量可以预测 FASD 儿童和健康对照儿童的抑制功能。项目 5 与该中心的其他项目互补，涉及小鼠神经振荡以及项目 3 和 4 中检查的大鼠模型。此外，还将评估自主神经系统反应通过心率变异性来支持项目 2。这些项目结合起来将提供转化结果采取可衡量的步骤，为 FASD 儿童制定基于机制的干预措施。