CoFlu-Brain: An fMRI Connectivity Foundation Model with Cofluctuation-Based Pretraining
Authors: Ziteng Sui, Junfeng Xia, Wenhao Ye, Mo Wang, Quanying Liu
Organizations: Department of Biomedical Engineering, Southern University of Science and Technology, China · School of Biomedical Engineering, Shenzhen University, China · Department of Computer Science, University of Warwick, UK
Functional magnetic resonance imaging (fMRI) commonly characterizes large-scale brain organization through functional connectivity (FC). However, an observed FC matrix is not a fixed brain graph but a statistical estimate determined by the finite BOLD frames used to compute it. Conventional FC-based approaches typically represent each scan with a single Pearson-correlation matrix, leaving frame-resolved variations in regional interactions unexploited. To address this limitation, we introduce CoFlu-Brain, which organizes framewise cofluctuation observations into multiple retained and dropped views, each summarized as an FC matrix. The model learns connectivity structure reproducible across retained views and predicts the representations of the corresponding dropped views, while adopting SIGReg from LeJEPA to prevent representation collapse. We pretrained CoFlu-Brain on 13,444 subjects from eight dataset groups and evaluated its representations via frozen-encoder linear probing on seven classification and two age-prediction tasks across seven datasets. CoFlu-Brain showed strong transfer across demographic, developmental, and clinical prediction tasks, outperforming the evaluated released models on most tasks. Random frame partitioning improved aggregate transfer, while the complete objective achieved the strongest overall performance. Code is available.
Figures & tables
Figure 1: From a single FC estimate to cofluctuation based multi-view learning. Conventional FC aggregates all frames into a single connectivity estimate, whereas CoFlu-Brain uses different compositions of framewise cofluctuation observations to construct multiple FC views.
Figure 2: CoFlu-Brain pretraining and downstream evaluation. (a) Framewise cofluctuations from standardized regional BOLD signals. (b) Paired retained–dropped FC views train a shared encoder through consistency, latent prediction, and SIGReg. (c) Frozen-encoder linear probing and downstream inference.
Table 1: Linear probing of fMRI models for classification and age prediction. Values are mean ± sample SD across five participant-grouped folds. Classification tasks report accuracy and weighted F1 ( ↑ ); age-prediction tasks report nMAE ( ↓ ) and Pearson’s r ( ↑ ). Red boldface marks the best mean for each metric. CoFlu-Brain averages three pretrained checkpoints per fold; baselines use one released checkpoint. Overall rank test: cohort-blocked permutation p<0.001 .
Figure 3: Network-restricted probing on ADHD200. (a) Age nMAE ( ↓ ). (b) Diagnosis weighted F1 ( ↑ ). Cortical maps summarize mean performance across all 17 networks, and the corresponding point-range plots detail the five best-performing networks for each task. Points indicate individual pretraining seeds, diamonds indicate seed means, horizontal segments indicate seed ranges, and dashed vertical lines indicate whole-brain performance.
Figure 4: Random versus ordered frame partitioning. (a) Relative weighted-F1 gain for classification and relative nMAE reduction for age prediction; positive values favor random partitioning. (b) Mean weighted F1 across seven classification tasks. (c) Mean nMAE across two age-prediction tasks. Lines connect paired pretraining seeds; red diamonds denote seed means.
Dataset Objective
HCP / Sex
ADNI / AD
ADHD200 / Diagnosis
ADHD200 / Age
Weighted F1 ↑
Weighted F1 ↑
Weighted F1 ↑
nMAE ↓
Full
0.7874 ± 0.0115
0.7219 ± 0.0657
0.5872 ± 0.0215
0.6523 ± 0.0315
No prediction
0.6565 ± 0.0187
0.5023 ± 0.0850
0.5348 ± 0.0309
0.7416 ± 0.0567
No consistency
0.7789 ± 0.0110
0.6866 ± 0.1175
0.5725 ± 0.0384
0.6611 ± 0.0539
No SIGReg
0.6942 ± 0.0153
0.6065 ± 0.0667
0.5643 ± 0.0288
0.7132 ± 0.0482
Cohort-averaged rank: Full 1.50; No prediction 3.57; No consistency 1.79; No SIGReg 3.14
Table 2: Downstream performance under objective-component ablation. Each objective variant was pretrained independently with seed 42 under matched configurations and is reported as mean ± SD across five participant-grouped folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task. Overall rank test: cohort-blocked permutation p=0.0014 .
Table 3: Pretraining data coverage and downstream performance. Values are mean ± SD across probe folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Table 4: Downstream performance by temporal branch count. Values are mean ± SD across probe folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Table 5: Downstream performance under consistency-weight schedules. Values are mean ± SD across probe folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Appendix figures & tables9 assets
Supplementary material from the paper’s appendix.
Appendix
Dataset / task
Participants
Examples
Target
HCP sex
1,000
5,997
Binary sex
ABCD sex
500
999
Binary sex
PPMI group
474
1,896
Three diagnostic groups
ADNI AD
230
230
AD vs. control
ADNI MCI
292
292
MCI vs. control
ABIDE ASD
173
173
ASD vs. control
Appendix
Table 6: Downstream evaluation cohorts and prediction targets. Participants are grouped across all available segment-level examples when constructing cross-validation folds.
Configuration
Value
Model configuration
Input representation
ROI atlas
Schaefer-400
Input segment length
200 frames
FC-row embedder
MLP dimensions
400→512→128→512
Appendix
Table 7: CoFlu-Brain model, pretraining, and linear-probe configurations.
Table 8: CoFlu-Brain linear probing across pretraining seeds. Values are mean ± sample SD across five participant-grouped folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). The final column averages scores across the three pretraining seeds within each fold before computing mean ± SD.
Network
ROIs
Age nMAE ↓
Diagnosis F1 ↑
DefaultA
34
0.6804 ± 0.0065
0.5965 ± 0.0165
ContC
12
0.6894 ± 0.0029
0.5619 ± 0.0132
LimbicA
13
0.6923 ± 0.0056
0.5442 ± 0.0047
DefaultC
13
0.7012 ± 0.0052
0.5288 ± 0.0125
SomMotA
39
0.7042 ± 0.0116
0.5435 ± 0.0226
LimbicB
11
0.7196 ± 0.0138
0.5372 ± 0.0092
Appendix
Table 9: Functional-network selection on ADHD200. Gray shading marks the top-five networks identified for each task by network-restricted probing. Values are mean ± SD across three independent pretraining runs. Age prediction reports nMAE ( ↓ ); diagnosis reports weighted F1 ( ↑ ). ROI counts indicate network size.
Table 10: Downstream performance under random and ordered frame partitioning. Each seed entry is mean ± sample SD across five participant-grouped folds. The final column averages scores across pretraining seeds within each fold before computing mean ± SD. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the better seed-averaged score for each task.
Table 11: Objective-component ablation across nine downstream tasks. Each objective variant was pretrained independently with seed 42 under matched configurations and is reported as mean ± SD across five participant-grouped folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Table 12: Pretraining data coverage and downstream performance across nine tasks. Values are mean ± SD across probe folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Table 13: Temporal branch-count comparison across nine downstream tasks. Values are mean ± SD across probe folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Table 14: Consistency-weight schedule comparison across nine downstream tasks. Values are mean ± SD across probe folds. Metrics are weighted F1 ( ↑ ) and age nMAE ( ↓ ). Red boldface marks the best mean for each task.
Self-supervised pretraining reshaped prediction in language and vision, and brain foundation models (BFMs) inherited its promise. Representations learned from large unlabelled corpora should capture individual functional dynamics and generalise across cohorts. However, kernel ridge regression (KRR) fitted on functional connectivity (FC) matrices still predicts individual phenotypes more accurately than any BFM we tested. In this paper, we show that KRR is weighted by the eigenvalues of the FC which are miscalibrated for phenotype prediction. We apply an efficient spectral filter to recalibrate the eigenvalues of each subject's FC matrix, enabling the model to exploit more inter-individual variance. Across the 5 datasets, 11 parcellations and 6 prediction targets we tested, we match or exceed the KRR baseline. Based on this finding, we then pretrain a small encoder model on about 4,000 hours of fMRI from 162 open datasets, whereby we align the pairwise similarities between the embeddings of recording snippets with those between the recalibrated connectomes. Our model performs on par with the best of the 6 published BFMs we tested while having an order of magnitude fewer parameters. Our encoder performs better than FC on short scans and in smaller cohorts, especially in fingerprinting. We release the pretrained model weights, the code and the pretraining data, preprocessed and parcellated.
Giovanni Marraffini, Victoria Shevchenko, Carlo Alberto Barbano +1
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 ∼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.
Giovanni Marraffini, Gabriel Mahuas, Trinidad Borrell +2
Inria Saclay Île-de-France, CEA, Université Paris-Saclay, Palaiseau, France · Sigma Nova · Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM +1
We study the problem of training self-supervised foundation models for functional MRI. Our main contributions are: (1) we introduce a new model family (CortexMAE) trained using the masked autoencoder framework on 2.1K hours of open fMRI data, and (2) we release the first open evaluation suite (Brainmarks) for fMRI foundation models. Our core innovation is simple: we adapt the Vision Transformer to fMRI by first converting each 3D fMRI volume to a 2D map using a cortical flat map projection. We directly compare flat maps to both parcellation and volume-based representations. While each has its advantages, flat maps generally perform best. We perform the first systematic scaling analysis for fMRI and observe strict power law scaling, albeit with limits. Finally, we use Brainmarks to do controlled benchmark comparisons. On subject-level trait prediction, we report a challenging null result: no single model achieves clear state-of-the-art performance. Moreover, all models struggle to outperform a simple functional connectivity baseline. On cognitive state decoding, we observe more robust performance, and in this setting our CortexMAE family outperforms prior models by a large margin. Code, models, and datasets are available at https://github.com/MedARC-AI/CortexMAE and https://github.com/MedARC-AI/Brainmarks.