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 ...