Benchmarking Synolitic Graphs for Autism Classification from Multisite Resting-State fMRI

Background/Objectives: Synolitic graphs (SGs) were developed for task-based fMRI, where edge weights encode the discriminative power of pairwise regional features; whether similar information can be recovered from resting-state data was untested. We benchmarked SGs for autism spectrum disorder (ASD) classification using the multisite ABIDE-I dataset (871 subjects: 403 subjects with ASD, 468 typical controls; 17 sites; CC200 atlas). Methods: Using 5-fold cross-validation with 10 repeats and balanced accuracy as the primary metric, we compared SGs with eight baselines including correlation matrices, tangent space connectivity, elastic net logistic regression, SVM, and XGBoost. Results: The vectorised correlation matrix achieved 67.9% balanced accuracy (AUC = 0.743), the combined model 68.0% (AUC = 0.744), and SGs 57.0% (AUC = 0.598). SGs performed above chance (permutation p = 0.001), but their performance was not significantly different from that of direct logistic regression (Nadeau–Bengio p = 0.82). After covariate residualisation, correlation-based methods retained 66.9–67.1% balanced accuracy, while SGs achieved 55.6%. Leave-one-site-out validation yielded 66.0–66.2% for correlation-based models and 55.0% for SGs, with similar declines of approximately 2 percentage points from standard cross-validation. SG-derived ROI rankings were unstable, and ADOS severity prediction among 193 ASD participants was underpowered and inconclusive. Conclusions: Conventional connectivity representations substantially outperformed SGs for resting-state ASD classification, contrasting with previously reported task-fMRI advantages. No evaluated method achieved performance suitable for stand-alone clinical screening or diagnosis; this study should therefore be interpreted as a methodological benchmark rather than a validation of a clinically deployable tool.