ERG-Graph: Graph Signal Processing of the Electroretinogram for Classification of Neurodevelopmental Disorders

Objective biomarkers for neurodevelopmental disorders remain an unmet clinical need. The electroretinogram (ERG), a non-invasive recording of the retinal response to light, has shown promise as a physiological marker for autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), yet existing classification approaches based on time-domain and time-frequency features achieve limited accuracy in clinically relevant multi-group scenarios. This study introduces ERG-Graph, a novel graph signal processing (GSP) framework that transforms each ERG waveform into a weighted, undirected graph through amplitude quantization and temporal-adjacency connectivity. Nine topological and spectral features, including total load centrality, clique number, algebraic connectivity, and clustering coefficient, were extracted from each graph to characterize the structural dynamics of the signal. Using light-adapted ERG recordings from 278 participants (ASD = 77, ADHD = 43, ASD + ADHD = 21, Control = 137), we evaluated these features across binary, three-group, and four-group classification scenarios using seven machine learning classifiers with 10-fold subject-wise cross-validation. The proposed ERG-Graph features achieved balanced accuracies of 0.91 (ASD vs. control, males) and 0.88 (ADHD vs. control, females). Critically, fusing ERG-Graph with time-domain features yielded a balanced accuracy of 0.81 for three-group classification (ASD vs. ADHD vs. control), representing an 11-percentage-point improvement over the previous benchmark of 0.70. Statistical analysis confirmed significant topological differences between groups (Kruskal-Wallis, p < 0.001; Cliff's delta: large effect sizes), and SHAP analysis revealed that graph-theoretic features dominated the top-ranked predictors. These results demonstrate that graph-based topological features capture discriminative information in the ERG waveform that is inaccessible to conventional signal analysis methods, advancing the development of objective biomarkers for neurodevelopmental disorder screening.