Assessing Cerebral Visual Impairment Through Non-Verbal Responses: Protocol Development and Feasibility of EchoCue

Technical Summary: Assessing Cerebral Visual Impairment Through Non-Verbal Responses: Protocol Development and Feasibility of EchoCue™

Problem Statement
Cerebral Visual Impairment (CVI) is a leading cause of childhood disability in high-income countries, yet current screening tools are largely inaccessible to the most severely affected children. Existing protocols typically require active participation and verbal instruction, which excludes children with significant neurodevelopmental delays. Furthermore, the symptomatic overlap between CVI and Autism Spectrum Disorder (ASD)—including atypical eye contact and sensory responses—often leads to misdiagnosis or delayed identification of visual deficits. There is an urgent need for an objective, non-verbal assessment methodology that can evaluate foundational sensory processes without relying on a child's active cooperation or cognitive performance.

Methodology
This paper outlines the Stage 1 protocol for a feasibility study of EchoCue™, a novel, non-invasive screening paradigm designed for children aged 2 to 6. The study is structured as a Registered Report with an exploratory, estimation-focused design.

• Study Design & Participants: The study plans to recruit 45 participants divided into three age- and sex-matched groups (n=15 per group): children with a clinical diagnosis of CVI, a clinical control group with ASD (no visual impairment), and a typically developing (TD) control group. No exclusion criteria are applied based on cognitive or intellectual levels to ensure the tool's applicability across the full spectrum of CVI severity. Adaptive functioning will be controlled for using the Vineland-3 parent-report scale.
• The EchoCue™ Paradigm: The protocol utilizes a multimodal approach combining calibrated auditory and visual stimuli with the recording of involuntary reflex responses.
  • Hardware: The system uses an iPad Pro (2021 or later) with the TrueDepth infrared camera for eye-tracking and a millimeter-wave (mmWave) radar sensor for motion detection.
  • Stimuli: Auditory stimuli include pure tones (500 Hz and 2000 Hz) presented at 70 dB SPL. Visual stimuli consist of unilateral LED flashes (40 ms duration).
  • Protocol Structure: The session (12–15 minutes) includes three core blocks:
    1. Auditory-only: Lateralized sounds to evoke orienting and startle reflexes.
    2. Visual-only: Unilateral flashes to assess primary visual pathways.
    3. Congruent Audiovisual: Synchronized sound and flash in the same hemifield to measure multisensory integration.
• Key Metrics:
  • Saccadic Reaction Time (SRT): Calculated from eye-tracking data (60 Hz frame rate) as the time between visual target onset and saccade onset (defined by a velocity threshold of 30°/s).
  • Startle Amplitude: Measured via mmWave radar as peak motion energy within 40–200 ms of auditory onset, normalized against a pre-stimulus baseline.
• Analysis Plan: The study prioritizes estimation over null-hypothesis testing. Linear Mixed-Effects Models (LMM) will be used to estimate group differences in SRT and audiovisual enhancement effects, reporting effect sizes with 95% Confidence Intervals (CIs). A preliminary feasibility check (n=5 per group) will precede full recruitment to optimize calibration.

Key Contributions

• Non-Verbal Assessment Framework: EchoCue™ offers a method to assess neurovisual function without requiring verbal instruction or active task compliance, specifically targeting populations traditionally difficult to assess.
• Multimodal Reflex Integration: The protocol uniquely combines auditory probes (ranging from subcortical low frequencies to cortical high frequencies) with visual stimuli to measure how the brain integrates sensory inputs, providing an indirect index of visual processing via the modulation of non-visual reflexes.
• Accessible Technology: The system leverages consumer-grade hardware (iPad TrueDepth camera and mmWave radar) to create a portable, low-cost screening tool, aiming to democratize access to objective CVI assessment.
• Feasibility Metrics: The study establishes rigorous criteria for feasibility, including completion rates, behavioral tolerance (distress coding), and parent acceptability, alongside data quality thresholds (e.g., 60% valid trials per participant).

Results
As this is a Stage 1 Registered Report (Protocol Development), the paper does not present empirical results or data analysis outcomes. The document serves as the pre-registered plan for the study. It outlines the theoretical rationale, experimental design, and statistical analysis strategy intended to generate robust estimates of effect sizes and feasibility indicators for a future large-scale confirmatory trial.

Significance and Claims
The authors position this study as a critical first step toward addressing a major gap in pediatric neurology. The significance of the work lies in its potential to:

1. Enable Early Detection: Provide an objective tool for identifying CVI in children who cannot participate in standard behavioral tests, potentially reducing delays in care.
2. Improve Differential Diagnosis: Offer distinct physiological markers to help differentiate CVI from ASD, addressing the current challenge of symptomatic overlap.
3. Validate Novel Methodologies: Demonstrate the feasibility of using consumer-grade eye-tracking and mmWave radar for capturing subtle, non-contact neurological reflexes in a clinical pediatric setting.

The paper maintains a modest tone, acknowledging that the current sample size is small and the study is exploratory. It explicitly states that the primary goal is to generate effect size estimates and confidence intervals to inform the design of future, larger-scale validation trials, rather than to establish definitive diagnostic norms at this stage. The authors also note limitations regarding the use of prior clinical diagnoses (potential misclassification) and the uncontrolled nature of variables like IQ and visual acuity, which will be addressed in future research.