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

项目总结 患有自闭症谱系障碍(ASD)的儿童、青少年和成年人--一种高度可变的障碍--通常 难以完成复杂的现实任务，影响日常生活。目前还不清楚这些困难的程度 源于基本的“低水平”神经对运动系统的妥协，而不是“高水平”的认知 可以通过执行功能的过程来调节电机性能的控制系统。有神经性的 运动皮质功能和执行功能的特征可以从 脑磁图(MEG)记录运动时的β-频段振荡活动(15-30赫兹) 运动系统和前额叶的theta频段(4-8赫兹)活动(执行功能的神经底物) -额叶内侧丘脑，FMT。最近的研究表明，人与人之间的差异 青少年ASD的一种称为运动后β反弹(PMBR)的成分，不久就会发生 跟随着简单的动作。然而，这些研究与大多数文献一样，询问了 马达系统通过实验上方便，但很难推广的“按钮按下”响应，几乎 与现实生活中的行为相关。一个与青少年生活质量密切相关的现实生活行为是 汽车驾驶。自闭症青少年在获得适当的驾驶技能方面面临的挑战(例如 速度控制和车道维护)对他们从青春期到 独立的成年期。这些“运动”损伤是源于“低水平”运动皮质还是“高水平”运动皮质 然而，使用简单的视觉提示按钮按下任务并不容易评估认知控制。我们 充分利用最近开发的与MEG兼容的驾驶模拟器技术，包括逼真的软件 和光纤硬件来评估ASD青少年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期(TD)对照。我们收养了一个毕业的 实验设计，其中任务要求和背景被操纵，以增加生态有效性 这些范例--从简单的按下按钮--由“驾驶相关”的交通信号灯提示，到利用 模拟器硬件(踏板/方向盘)用于评估逼真的“移动”驾驶模拟。在每一种情况下， 响应将使用相同的提示(红绿灯时的“停止”、绿色箭头的“转弯”等)。仅在 情况的背景各不相同。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(例如，在目标跟踪期间或 “受控”刹车/转向)，我们假设在ASD中会减少这一点。我们预计那个人 在PMBR、FMT和相幅耦合(FMT和马达伽马频段(PAC)之间)的差异 患有自闭症的人会预测驾驶性能。这架R21将建立一个生态有效的探测 ASD的可变性，也可能为推广到其他复杂的视觉运动提供一个框架 过程和行为，不太容易直接进行神经研究。

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.