MEG evaluation of motor and cognitive control impairments underlying driving performance in ASD

项目摘要 患有自闭症谱系障碍（ASD）的儿童，青少年和成人-一种高度可变的疾病-通常有 难以完成复杂的现实任务，影响日常生活。目前尚不清楚这些困难在多大程度上 源于基本的“低级别”神经妥协的运动系统相比，“高级别”认知 通过执行功能过程调节运动性能的控制系统。有神经 运动皮层功能和执行功能的特征，可以从 运动期间的脑磁图（MEG）记录：大脑皮层的β带振荡活动（15- 30 Hz） 运动系统和前额叶的θ波段（4-8Hz）活动（执行功能的神经基质） - 额内θ最近的研究表明， 患有ASD的青少年称为运动后β反弹（PMBR）， 简单的动作。然而，这些研究与大多数文献的共同点是， 运动系统通过一个实验方便，但概括性差的“按钮按下”的反应， 与现实生活中的行为相关。一个与青少年生活质量显著相关的现实生活行为是 汽车驾驶。ASD青少年在获得足够的驾驶技能方面面临的挑战（例如， 速度控制和车道维护）严重限制了他们从青少年过渡到 独立的成年这些“运动”障碍是源于“低级”运动皮层还是“高级” 然而，认知控制不能使用简单的视觉提示按钮按压任务容易地评估。我们 利用最近开发的MEG兼容驾驶模拟器技术，包括逼真的软件 和光纤硬件来评估青少年ASD患者的低水平和高水平功能特征 （N=20，15- 17.99岁）和年龄/性别匹配的典型发育（TD）对照。我们采用一个毕业的 实验设计，其中任务要求和背景被操纵，以增加生态效度， 范例-从简单的按钮按下提示“驾驶相关”交通灯信号，通过利用 模拟器硬件（踏板/方向盘），以评估现实的“移动”驾驶模拟。在每种情况下， 将使用相同的提示（在红灯处“停止”，在绿色箭头处“转向”等）获得响应。只有 情况的背景不同。我们预计ASD患者的PMBR会降低。在TD青少年中，我们预计 随着认知控制需求的增加，FMT升高（例如，在目标跟踪或 “受控”制动/转向），我们假设其在ASD中减少。我们预计那个人 PMBR、FMT和相位振幅耦合（FMT和运动伽马波段（PAC）之间）的差异， ASD患者将预测驾驶性能。这一R21将建立一个生态有效的探针， ASD的变异性，也可以提供一个框架，推广到其他复杂的视觉运动 过程和行为，不太适合直接神经研究。

PROJECT SUMMARY Children, adolescents and adults with autism spectrum disorder (ASD)—a highly variable disorder—often have difficulty with complex real-world tasks, impacting day to day life. It is unclear the extent to which these difficulties stem from fundamental “low-level” neural compromise to the motor system compared to “higher level” cognitive control systems that may mediate motor performance through processes of executive function. There are neural signatures of both motor cortex function and executive function that can be determined from magnetoencephalographic (MEG) recording during movements: beta-band oscillatory activity (15-30Hz) of the motor system and theta-band (4-8Hz) activity of the anterior frontal lobe (neural substrates of executive function) – frontal medial theta, FMT. Recent studies have demonstrated diminution and inter-individual variability in adolescents with ASD of a component termed post-movement beta rebound (PMBR), which occurs shortly following simple movement. However, these studies in common with the majority of the literature interrogate the motor system via an experimentally-convenient, but poorly generalizable “button press” response, of little relevance to real-life behavior. One real-life behavior of significant relevance to adolescent quality of life is automobile driving. The challenges faced by adolescents with ASD in acquiring adequate driving skills (e.g. speed regulation and lane maintenance) pose a severe limitation to their transition from adolescence to independent adulthood. Whether these “motor” impairments stem from “low-level” motor cortex or “high-level” cognitive control cannot, however, be readily assessed using simple visually-cued button-press tasks. We capitalize on recently-developed MEG-compatible driving simulator technology, including both realistic software and fiber-optic hardware to assess both low-level and high-level functional signatures in adolescents with ASD (N=20, 15-17.99yrs) and age/sex-matched typically developing (TD) controls. We adopt a graduated experimental design in which task-demands and context are manipulated to increase the ecological validity of the paradigms – from simple button-presses cued by “driving-relevant” traffic light signals, through utilization of simulator hardware (pedals/steering wheel) to assess realistic “moving” driving simulation. In each case, responses will be obtained using identical cues (“stop” at red traffic light, “turn” on green arrow, etc.) with only the context of the situation varying. We anticipate decreased PMBR in ASD. In TD adolescents we anticipate the emergence of elevated FMT with increasing demand for cognitive control (e.g. during target tracking or “controlled” braking/steering), which we hypothesize to be diminished in ASD. We anticipate that individual differences in PMBR, FMT and phase-amplitude coupling (between FMT and motor gamma-band (PAC)) in individuals with ASD will predict driving performance. This R21 will establish an ecologically valid probe of variability in ASD and may also provide a framework for generalization to other complex visuo-motor processes and behaviors, less amenable to direct neural study.