Inferring continuous cognitive traits from limited neuroimaging data using pairwise convolutional neural networks

Objective cognitive assessment from neural signals supports neurorehabilitation, but individual-level prediction from task-based fMRI (tfMRI) remains difficult because neural features coexist with substantial demographic and scanner-related variation. We present the Multi-task Activation and Contrast Network (MAC-Net), a covariate-aware deep learning framework for modeling individual cognitive function from regional tfMRI. By isolating tfMRI features into a dedicated neural pathway and restricting participant variables to a terminal late-fusion pathway, MAC-Net prevents dominant covariates from suppressing high-dimensional clinical representations during feature learning. Evaluating baseline data from 6,500 Adolescent Brain Cognitive Development Study participants under family-aware cross-validation, MAC-Net was benchmarked against linear models, random forests, and alternative deep architectures. The N-back plus Monetary Incentive Delay configuration achieved $R^{2}$ values of 0.174, 0.238, and 0.277 for fluid, crystallized, and total cognition, outperforming covariate-only baselines (0.178) and alternative deep models (0.217). N-back was the most informative paradigm, whereas incorporating the Stop Signal Task marginally degraded performance. Feature attributions via Integrated Gradients, DeepLIFT, and Input Gradient were highly concordant, localizing working-memory-related frontal, parietal, and cingulate regions. These findings demonstrate that covariate-aware multi-task modeling yields reproducible cognitive-function estimations, establishing a robust neural engineering framework for clinical translation.

Mapping resting-state brain organization to individual differences in cognitive ability remains a major challenge in population neuroinformatics. Although deep learning enables flexible modeling of brain connectivity, limited interpretability restricts its scientific and clinical utility. To address this objective, we developed an explainable deep learning framework based on sparse projected residual networks to predict fluid, crystallized, and total intelligence from resting-state functional magnetic resonance imaging in 5,285 participants from the Adolescent Brain Cognitive Development study. We incorporated three complementary explainability methods (Integrated Gradients, Gradient Shapley Additive Explanations, and Occlusion) to interpret model behavior. The framework outperformed existing approaches, achieving Pearson correlations of 0.44, 0.58, and 0.56 for fluid, crystallized, and total intelligence, respectively, corresponding to predictive improvements of 6 to 9 percent. All three explainability methods produced near-identical feature rankings (pairwise rank correlations greater than 0.99). Consensus maps revealed a dual-layered functional architecture where primary predictive hubs localized within canonical systems, while the strongest global predictive pathways frequently bypassed these hubs through distributed, long-range relay connections. These findings suggest that intelligence emerges from the interaction between localized computational hubs and distributed communication pathways. Ultimately, these normative network architectures provide clinical reference maps to detect individual deviations, supporting earlier diagnosis, cognitive subtype stratification, and treatment monitoring in atypical neurodevelopment.

Deep learning models for neuroimaging have largely been developed for individual tasks, limiting knowledge transfer across applications. Here we introduce GenFAR, a modular deep learning framework that learns general, clinically informed features from brain MRIs. We trained this modular architecture on 49,246 individuals across 11 cohorts, using 17 diverse classification and regression tasks spanning cognition, clinical, diagnosis, demographics, and biomarkers. This yields aggregated, focused feature sets that capture rich, clinically- and biologically-relevant brain representations. We developed a sequential learning approach where tasks progressively build on previously learned representations. Through an analysis of 5,000 task sequences, we identified an optimal sequence length of six tasks and introduced a Donor Score metric to quantify each task's contribution to downstream performance. This analysis revealed five consistently strong donor tasks (Age, AD/MCI, MMSE, Hypertension, Hyperlipidemia) that formed the base of our sequential model. We demonstrated the utility of our learned representation, in various tasks beyond those included in the training set, to serve as the foundation for specialized secondary predictors. We further showed that using the learned feature representation can substantially increase the sample efficiency of secondary deep learning training tasks and models, as well as improve their accuracy.