Understanding neurophysiological deficits in response inhibition in children with FASD

摘要 对胎儿酒精谱系障碍的细微迹象的识别将估计患病率增加到 2-5%的学龄儿童。虽然FASD的神经认知特征已经被描述，但 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儿童发现的执行功能障碍之一，可能与 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障碍的易感性。因此，理解潜在的 导致小学早期儿童抑制功能受损的大脑机制对 指导干预方法的发展。在其他临床人群中，功能网络改变 用功能磁共振成像评估的连接性与抑制功能较差有关。另一大堆工作 主要来源于脑电的研究表明，神经振荡在认知控制和调节中起着关键作用 抑制反应。通过使用脑磁图，我们将通过以下方式将这些先前的脑电结果扩展到FASD人群 识别诱发活动的皮层来源位置和定时，并检查休眠网络连通性 在源代码级别。利用脑磁图的高时间分辨率，我们将捕捉到静止的神经振荡， 静息的大脑连接和任务诱发的神经振荡与成功和不成功有关 对儿童友好的Go/No Go任务期间的抑制。这个项目期间将检查6-8岁的年幼儿童 年龄范围和使用脑磁图的神经振荡和使用两者的功能网络连接性的重点 脑磁图和功能磁共振成像。目标1将使用脑磁图检查事件相关反应，包括平均诱发反应 以及在进行/不进行任务时的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 在当前项目期内在较年轻的独立队列中获得的诱发反应结果，并将扩大 前一个项目阶段的目标是检查任务诱发的神经振荡，允许我们捕获theta和beta 与认知控制有关的振荡。目标2将检查静息神经振荡和静息功能 同时使用脑磁图和功能磁共振成像进行网络连接。最近的研究结果表明，静息功能网络 连接模式因临床疾病而异。目标3将通过链接结果来直接研究这个问题 从目标1和目标2以及这些儿童抑制功能的行为测量来确定 什么大脑功能指标可以预测FASD儿童和健康对照组的抑制功能。 项目5与中心的其他项目相辅相成，资助小鼠的神经振荡 以及在项目3和4中检查的大鼠模型。此外，将评估自主神经系统反应 通过心率变异性支持项目2。这些项目结合在一起，将提供翻译结果 采取可衡量的步骤，为FASD儿童制定基于机械的干预措施。

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.