Functional connectome analysis examines brain-region interactions to understand and identify disorders such as autism spectrum disorder and Alzheimer's disease. Existing methods typically use GNNs and Transformers to model the full functional connectivity matrix. However, processing tens of thousands of connections introduces redundancy and noise, increases computational cost, and limits connection-level interpretability. This raises a central question: do we really need complex interaction modeling, or is identifying a small set of disease-relevant connectivity patterns sufficient? To answer this question, we propose BrainLinear, a lightweight geometry-aware framework for mining disease-discriminative connectome patterns. BrainLinear first maps each functional connectivity matrix to a shared tangent space centered at the Fréchet mean of the training set, capturing subject-specific deviations while respecting matrix geometry. It then scores each ROI-pair tangent direction by its classification contribution and disease--control difference, retaining Top-K directions as a compact representation. Finally, a shallow multilayer perceptron performs classification on the selected representation. Experiments on ABIDE and ADNI show that BrainLinear matches or exceeds strong GNN and Transformer baselines at a fraction of their cost: it improves AUC and ACC over the best baseline for each metric by up to 3.54 and 1.39 percentage points, while reducing runtime and peak GPU memory by 84.0% and 68.4% relative to the closest baseline in AUC. The selected directions are directionally consistent with between-group displacements and organized across major functional systems, supporting connection-level interpretation.
Figures & tables
Figure 1: Overview of BrainLinear. Functional connectomes are mapped to a shared AIRM tangent space, where disease-discriminative ROI-pair coordinates are selected by joint probe relevance and group displacement for lightweight classification.
Model
ABIDE
ADNI
AUC ↑
ACC ↑
SEN ↑
SPE ↑
AUC ↑
ACC ↑
SEN ↑
SPE ↑
GNN
BrainGNN
64.42 ± 3.57
63.09 ± 1.35
65.65 ± 2.88
60.67 ± 3.68
61.81 ± 1.58
58.72 ± 3.14
52.88 ± 9.70
62.70 ± 4.26
BrainGB
70.32 ± 3.66
65.12 ± 3.90
67.01 ± 10.00
60.07 ± 8.53
66.44 ± 3.33
63.70 ± 4.65
60.73 ± 8.25
64.67 ± 9.07
FBNetGen
74.50 ± 3.77
67.09 ± 3.37
64.71 ± 9.85
69.61 ± 9.30
67.05 ± 2.16
63.26 ± 1.38
66.79 ± 6.93
61.31 ± 9.65
GCN
59.59 ± 3.44
59.30 ± 3.38
56.67 ± 4.37
61.55 ± 5.29
62.45 ± 3.63
59.12 ± 4.53
54.55 ± 9.96
62.00 ± 8.55
GAT
60.43 ± 3.88
60.10 ± 4.13
59.26 ± 5.51
62.89 ± 8.03
62.00 ± 2.88
58.75 ± 2.86
53.20 ± 7.50
64.79 ± 7.65
Table 1: Classification performance comparison. Best results are in bold with shaded cells; second best are underlined .
Variant
ABIDE
ADNI
AUC ↑
ACC ↑
SEN ↑
SPE ↑
AUC ↑
ACC ↑
SEN ↑
SPE ↑
Raw FC + MLP
65.41 ± 3.15
60.80 ± 2.13
58.66 ± 5.63
62.00 ± 7.60
67.47 ± 13.88
58.33 ± 12.84
63.33 ± 35.17
56.38 ± 16.21
Full Tangent + MLP
77.30 ± 1.31
67.62 ± 2.49
82.45 ± 3.41
53.65 ± 7.43
70.61 ± 3.78
64.75 ± 3.16
62.42 ± 6.27
67.03 ± 11.05
Random- K Tangent + MLP
72.06 ± 1.83
63.66 ± 1.24
74.08 ± 7.99
53.85 ± 9.81
65.29 ± 4.64
60.50 ± 4.99
60.94 ± 10.75
60.01 ± 13.87
Coefficient-only Top- K
76.48 ± 1.13
67.92 ± 3.63
73.27 ± 10.29
62.88 ± 16.00
70.41 ± 3.75
64.36 ± 3.96
72.37 ± 8.66
56.80 ± 13.53
Displacement-only Top- K
77.68 ± 0.83
68.61 ± 1.74
79.80 ± 2.54
58.08 ± 5.29
70.68 ± 4.41
64.75 ± 2.70
69.71 ± 15.58
60.05 ± 14.69
Table 2: Ablation results on ABIDE and ADNI (%). Best results are in bold with shaded cells; second best are underlined .
Figure 2: Performance-efficiency comparison on ABIDE.
Figure 3: Sensitivity analysis under different sparsity budgets.
Figure 4: Discriminative relevance across tangent coordinates.
Figure 5: Validation of selected tangent directions on ABIDE.
Figure 6: Biological interpretation of tangent directions.
Figure 7: Brain-space distribution of tangent directions.
Appendix figures & tables3 assets
Supplementary material from the paper’s appendix.
Appendix
Feature
Classifier
ABIDE
ADNI
AUC ↑
ACC ↑
SEN ↑
SPE ↑
AUC ↑
ACC ↑
SEN ↑
SPE ↑
Raw FC
Logistic
65.41
60.80
58.66
62.00
66.14
60.83
51.56
66.76
SVM
68.57
62.34
52.35
71.90
62.38
57.50
59.56
55.62
MLP
69.17 ± 4.11
63.93 ± 2.31
54.37 ± 10.22
73.06 ± 7.90
67.97 ± 6.49
59.17 ± 8.25
63.33 ± 19.85
55.90 ± 23.15
Full Tangent
Logistic
73.34
66.20
56.38
75.58
67.47
58.33
63.33
56.38
SVM
73.21
66.60
58.41
74.41
68.28
59.17
43.11
70.29
Appendix
Table 3: Effect of classifier choice on different feature representations. Best results are highlighted in bold with shaded cells.
Rank
ROI Pair
Network Pair
Δe
αe
Importance
Direction
1
Precentral_L–Occipital_Mid_L
Somatomotor–Unassigned
0.0405
0.3167
0.0128
Positive
2
Hippocampus_R–Frontal_Sup_L
Frontoparietal–DefaultMode
-0.0343
-0.3740
0.0128
Negative
3
Caudate_L–Caudate_R
Somatomotor–Limbic
-0.0514
-0.2431
0.0125
Negative
4
Frontal_Mid_L–Temporal_Mid_L
Frontoparietal–Visual
-0.0431
-0.2761
0.0119
Negative
5
Cerebelum_Crus1_R–Lingual_L
Unassigned–Limbic
0.0355
0.3331
0.0118
Positive
6
Frontal_Med_Orb_L–Precuneus_L
Somatomotor–Visual
-0.0376
-0.3073
0.0115
Negative
Appendix
Table 4: Top-ranked discriminative tangent directions identified by BrainLinear. The importance score is defined as se=∣αeΔe∣ .
Pattern
Directions
Importance
Δ>0,α>0
4089
7.2430
Δ<0,α<0
3905
6.9698
Δ>0,α<0
4
0.0024
Δ<0,α>0
2
0.0013
Appendix
Table 5: Sign consistency analysis of selected discriminative tangent directions.
We present Supervised Deep Multimodal Matrix Factorization (SD3MF), an interpretable framework for integrative brain network analysis that generalizes Symmetric Nonnegative Matrix Tri-Factorization (SNMTF) from unsupervised single-graph clustering to supervised prediction over populations of multimodal graphs. SD3MF learns deep hierarchical factorizations for each modality together with a shared latent representation that aligns subjects across views. An encoder-decoder formulation jointly optimizes graph reconstruction and supervised prediction, while adaptive weights enable data-driven multimodal fusion. By representing each subject through community-level interaction matrices, the model yields interpretable and discriminative features. Experiments on multimodal connectome datasets show that SD3MF consistently outperforms strong deep learning baselines such as CNNs and GNNs, while enabling biologically interpretable insights. Code for reproducibility is available at: https://github.com/amjadseyedi/SD3MF.
Amjad Seyedi, Lifang He, Songlin Zhao +2
Dept. of Mathematics & Operational Research University of Mons, Mons, Belgium · Dept. of Computer Science & Engineering Lehigh University, Bethlehem, PA, USA · Dept. of Industrial & Systems Engineering Lehigh University, Bethlehem, PA, USA
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.
Ziteng Sui, Junfeng Xia, Wenhao Ye +2
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
Modeling the complex interactions among functional subnetworks is crucial for the diagnosis of mental disorders and the identification of functional pathways. However, learning the interactions of the underlying subnetworks remains a significant challenge for existing Transformer-based methods due to the limited number of training samples. To address these challenges, we propose KD-Brain, a Prior-Informed Graph Learning framework for explicitly encoding prior knowledge to guide the learning process. Specifically, we design a Semantic-Conditioned Interaction mechanism that injects semantic priors into the attention query, explicitly navigating the subnetwork interactions based on their functional identities. Furthermore, we introduce a Pathology-Consistent Constraint, which regularizes the model optimization by aligning the learned interaction distributions with clinical priors. Additionally, KD-Brain leads to state-of-the-art performance on a wide range of disorder diagnosis tasks and identifies interpretable biomarkers consistent with psychiatric pathophysiology. Our code is available at https://anonymous.4open.science/r/KDBrain.
Siyu Liu, Guangqi Wen, Peng Cao +4
Computer Science and Engineering, Northeastern University, Shenyang, China · Key Laboratory of Intelligent Computing in Medical Image of Ministry of Education, Northeastern University, Shenyang, China · School of Computer Science and Artificial Intelligence, Shandong Normal University, Jinan, China +5