Brain-Behavior Modeling from Multimodal MRI using Opportunistic Pretraining and Common-Cohort Adaptation

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.

Brain foundation models (BFMs) are self-supervised Transformers pretrained on fMRI data. We posit that these models should capture each subject's cognitive performance from their fMRI signal. Yet across three state-of-the-art BFMs and every readout we test, they predict cognition worse than a linear regression from the $\sim$80K parameters of the functional connectivity matrix (FC). The gap widens with scale: BrainLM's 650M model predicts cognition worse than its 111M. We attribute this to a variance allocation problem: BFM pretraining captures the variance components that dominate fMRI but not the higher-order structure that predicts cognition. Our per-cumulant analysis of the reconstructed signal shows that the second-order covariance is partially preserved, while the third-order co-skewness tensor is largely destroyed. To recover what BFMs lose, we design a linear pipeline that projects the fMRI signal into the subspace that best preserves its co-skewness and computes FC there. This exceeds raw FC and every pretrained BFM on every dataset and parcellation we test, outperforming prior state-of-the-art under controlled evaluation with no pretraining and no GPU. We recover the raw-FC ceiling on BrainLM's forward pass by finetuning with a loss targeted at this same subspace. This shows that the bottleneck is the pretraining objective, not the architecture or the model size.

Multi-modal fusion is of great significance in neuroscience which integrates information from different modalities and can achieve better performance than uni-modal methods in downstream tasks. Current multi-modal fusion methods in brain networks, which mainly focus on structural connectivity (SC) and functional connectivity (FC) modalities, are static in nature. They feed different samples into the same model with identical computation, ignoring inherent difference between input samples. This lack of sample adaptation hinders model's further performance. To this end, we innovatively propose a multi-stage dynamic fusion strategy (M3D-BFS) for sample-adaptive multi-modal brain network analysis. Unlike other static fusion methods, we design different mixture-of-experts (MoEs) for uni- and multi-modal representations where modules can adaptively change as input sample changes during inference. To alleviate issue of MoE where training of experts may be collapsed, we divide our method into 3 stages. We first train uni-modal encoders respectively, then pretrain single experts of MoEs before finally finetuning the whole model. A multi-modal disentanglement loss is designed to enhance the final representations. To the best of our knowledge, this is the first work for dynamic fusion for multi-modal brain network analysis. Extensive experiments on different real-world datasets demonstrates the superiority of M3D-BFS.