Background <p>Autism Spectrum Disorder (ASD) is characterized by differences across multiple intertwined functional domains, including cognitive, sensory, and motor processes. There is a need to understand how concurrent demands in different domains can impact performances in one another, as the simultaneous processing and execution of tasks from different domains is how most normal daily tasks and activities are completed. Differences in integration are thought to underly many characteristics of ASD, and therefore understanding how the brain processes multi-modal demands in both typically and neurodivergently developing populations is vital, and revealing how neural activity adapts to meet multi-modal demands can serve as valuable markers for supporting diagnosis and treatment decisions.”</p> Methods <p>We used Mobile Brain-Body Imaging (MoBI) to simultaneously record 64 channel electroencephalography (EEG), motion-tracking, and response inhibition task performance in adolescents (ages 13–23, mean 16.96 years) who have ASD and typically developing (TD) counterparts. We designed experimental conditions that either did or did not include a motor demand (standing or treadmill walking), sensory demand (static field or optical flow), and cognitive demand (completing task or not) to investigate single, dual, and tri-modal impacts on ERPs, gait kinematics, and task accuracy and speed.</p> Results <p>The TD group was significantly more accurate when walking. The ASD group did not increase task accuracy despite making similar adjustments to response speed when going from standing to walking. Optic flow did not impact task accuracy or for either group but did impact response speed. Similarly, walking impacted N200 and P300 amplitudes and latencies, but the addition of visual flow did not further these impacts. The ASD group’s neural activity showed differences that were similar in direction but weaker in magnitude to the addition of more demands (walking and flow), compared to the TD group.</p> Conclusions <p>There is a complex interplay between motor, cognitive, and sensory functions and we provide evidence here that cross-domain integration of these in adolescents is different in ASD than those who are typically developing. These results suggest that coupled neural and gait responses during multi-modal demands may serve as a potential marker of altered cross-domain integration in adolescents with ASD. Future research should further investigate these relationships with multi-modal methods like MoBI.</p>