An adaptive technical and behavioral approach for biomarker acquisition in autism with intellectual disability

Autistic individuals with intellectual disability (ASD+ID) and profound autism are rarely studied in neuroscience research due to barriers including communication challenges, sensory sensitivities, anxiety, and elevated behavioral support needs. Consequently, biomarker development in autism fails to include the portion of the autistic population with highest support needs and greatest potential to benefit from treatments derived from imminent advances in personalized medicine. Here we present a multimodal, participant-centered protocol for simultaneous electroencephalography (EEG) and eye-tracking (ET) acquisition to advance clinical trial readiness research in this underserved population. The protocol combines individualized behavioral supports and an adaptive EEG-ET acquisition platform. Pre-visit caregiver interviews informed participant-specific research plans, including customized visual supports, reinforcement strategies, and EEG net desensitization procedures. A gaze-contingent stimulus presentation system used participant-preferred videos to support attention to experimental stimuli and behavior consistent with data acquisition (e.g., refraining from movement) while dynamically adapting stimulus delivery based on visual engagement with the assay and real-time assessment of data quality. By quantifying attended trials in real time and prioritizing unattended stimulus classes, the paradigm maximizes acquisition efficiency to minimize participant burden. This approach was utilized to deploy candidate biomarkers with demonstrated replicability in the Autism Biomarkers Consortium for Clinical Trials (ABC-CT): the N170 event-related potential to faces, resting-state EEG, and visual attention to human faces (measured with ET). Feasibility was evaluated in 76 children with ASD+ID (M age = 8.76 years; IQ = 32.4) and a small comparison sample of 8 children with intellectual disability without autism (M age = 8.91 years; IQ = 45.9). Usable EEG data (>7 minutes) were acquired in 61% (ASD+ID) and 88% (ID) of participants, respectively. Sufficient ET data were obtained from 67% (ASD+ID) and 63% (ID) of participants, respectively. Findings demonstrate the feasibility of inclusive biomarker acquisition and provide a framework for expanding participation of individuals with ASD+ID and profound autism in neuroscience research. Ongoing research seeks to evaluate this approach in larger samples and to demonstrate feasibility in multisite research studies.