Brain Age Prediction

Latest papers 13

Sep 24, 2026cs.LG

Beyond Feature Reliability: Repeat-Informed Multifractal Curve Regression for Brain-Age Prediction

Brain-age prediction from resting-state fMRI provides a quantitative framework for characterizing age-related changes in spontaneous brain dynamics and for identifying functional signatures. Existing studies have linked fractal and multifractal scaling to age and examined the reliability of individual features. However, prediction repeatability depends on how features fluctuate jointly and how a predictor combines them, which feature-wise reliability assessments do not capture. To address this problem, we propose Repeat-informed Multifractal Curve Regression (RMCR), a structured framework for learning stable age-predictive patterns from multifractal curves. By jointly modeling curve structure and repeat-scan variability, RMCR learns predictive combinations of fluctuation orders that target both accuracy and within-subject consistency. Relative to a matched run-level ridge baseline, RMCR reduces single-run MAE by 6.1% on HCP-A and 7.9% on an external Cam-CAN cohort, and within-visit repeat absolute difference by 18.5% on HCP-A, using a single scan at inference.
Sep 11, 2026cs.CV

Brain-PACE: A Deep Siamese MRI Framework for Modelling Longitudinal Brain Acceleration

Brain age estimation has become a popular research proxy for assessing brain health and disease, yet longitudinal trajectories of brain ageing are still poorly defined, and clinical use is limited. Building on existing Siamese longitudinal frameworks, we develop Brain-Predicted Age Acceleration (Brain-PACE) to directly estimate the pace of structural brain ageing from paired T1-weighted MRI. Brain-PACE identified accelerated ageing in 42.642.6% of participants with mild cognitive impairment. Faster Brain-PACE was associated with greater functional and cognitive impairment (FAQ; r=0.35r=0.35, ADAS13; r=0.30r=0.30, CDR-SB; r=0.32r=0.32) and greater regional tau burden in the posterior cingulate (r=0.59r=0.59), precuneus (r=0.47r=0.47), and entorhinal cortex (r=0.37r=0.37). These associations were stronger than those observed when pace was calculated indirectly from repeated cross-sectional brain age estimates, suggesting that direct longitudinal modelling captures complementary information relevant to ongoing pathological change. Methodologically, Brain-PACE extends the LILAC framework by combining spatial attention with soft label distribution learning and a Cram'er distance objective, improving probabilistic performance and reducing prediction bias while providing measures of predictive uncertainty. Together, these findings support Brain-PACE as a complementary longitudinal imaging phenotype with sensitivity to relevant clinical and biological changes in early neurodegeneration.
Sep 9, 2026cs.LG

Learning with Covariance Matrices: Principal Component Analysis Meets Learning with Graphs

This feature article provides an overview of the theoretical foundations for coVariance neural networks (VNNs), i.e., graph neural networks (GNNs) operating on covariance matrices as graphs. Covariance matrices are ubiquitous across domains, and hence, the deployment of GNNs often leverages graphs of pairwise statistical dependencies. Existing theoretical contributions on GNNs consider abstract graph representations and cannot accommodate the data-driven nuances associated with covariance matrices. This tutorial brings into focus various novel theoretical insights via mathematical analyses of VNNs that have broad signal processing implications, including: (i) a conceptual equivalence between VNNs and principal component analysis (PCA)-based information processing; (ii) refined stability bounds on predictive outcomes in the presence of finite sample-induced covariance matrix perturbations; and (iii) refined characterization of transferability of VNNs across multiscale datasets. The theoretical insights discussed herein provide the underlying principles and justification towards adopting VNNs over workhorse PCA-based learning pipelines, in applications where covariance matrices are useful descriptors of data structure. We also convey how impact of these foundational advances permeates to \textit{principled} designs and applications of learning methods across broad domains where covariance matrices emerge. Notably, we elucidate the conceptual insights facilitated by VNNs to the specific task of characterizing brain age gap for neurodegenerative conditions using neuroimaging datasets, a timely problem in computational neuroscience. Broader impacts to other application domains are discussed as well.
Sep 8, 2026cs.LG

XAI-Refine: An Automated Explanation-Knowledge Loop for Brain-Age Prediction

Brain-age prediction models are commonly evaluated by predictive accuracy, yet accurate predictions alone do not establish that a model relies on reproducible or neurobiologically supported mechanisms. Post-hoc explanation methods can expose these mechanisms, but existing workflows typically stop at diagnosis or require correction targets to be specified before model analysis. We propose XAI-Refine, an automated explanation-knowledge loop for brain-age prediction from resting-state functional connectivity. At each iteration, XAI-Refine consolidates complementary post-hoc analyses across repeated training runs into reliable, structured model explanations. It converts each reliable explanation into a neutral neurobiological question, retrieves and verifies relevant literature, and compiles the verified evidence into an admissible set in the same typed explanation space. The target for refinement is defined as the minimal projection of the current model explanation onto the admissible set induced by applicable verified knowledge. This revised explanation is then translated into a differentiable constraint while preserving the originating model variable, measurement operator, and applicable scope. Candidate updates are promoted only when multi-seed validation confirms target-directed explanatory movement, predictive performance remains within a prespecified guardrail, and non-target explanatory drift remains bounded. Experiments on functional-connectivity-based brain-age prediction evaluate predictive performance, explanation reliability, literature alignment, and target-specific model revision, illustrating a structured route from post-hoc analysis to evidence-guided model refinement.
Sep 7, 2026cs.LG

Attributing Cohen's d: Training Data Attribution for Disease-Related Effects in Normative Age Biomarkers

Normative age models are trained to predict chronological age in a nominally healthy cohort. Applied to patients, they deviate, and the gap between predicted and chronological age is read as disease risk. Here, we attribute the disease-related effect size of the age gap directly to individual training samples, rather than using a prediction-level loss as the attribution target. For Cohen's dd, the resulting closed-form influence functional, validated against leave-one-out retraining, ranks training samples by their effect on held-out case-control separation. Across four diseases and two biomarker modalities in UK Biobank, removing the 10% most influential training samples raises held-out disease-related effect size in every seed. It more than doubles the metabolomic-age effect for type-2 diabetes and raises the brain-age effect for multiple sclerosis by roughly a third. Random removal leaves effect size flat even at 50% removal, confirming the gain comes from which samples are removed, not how many. Flagged subjects carry subclinical cardiometabolic burden that diagnosis-based exclusion misses, on markers the model never sees. For type-2 diabetes, where the method gains most, the marker recovered is HbA1c, the standard measure of blood sugar control. We release pyinfluence, our influence-function package, for reproducibility and reuse.
Aug 31, 2026eess.SP

Benchmarking External Generalization of SPD Matrix Learning for Resting-State fMRI Connectome Prediction

Resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity (FC) matrices are widely used for individual-level prediction, but strong performance within one cohort may not generalize to a new cohort. We ask whether within-dataset performance remains when the test data come from an entirely held-out rs-fMRI dataset. Each scan is represented as a regularized symmetric positive definite (SPD) correlation connectome, which allows methods to use the geometry of the SPD manifold. We introduce a reproducible age-prediction benchmark across six rs-fMRI datasets: COBRE, ADNIDOD, Cam-CAN, ABIDE, OASIS-3, and ADNI. The benchmark compares a vectorized correlation baseline, Tangent-Space Ridge, SPDNet, and split-wise Riemannian harmonization under within-dataset GroupKFold, pooled GroupKFold, and leave-one-dataset-out (LODO) evaluation. Within-dataset and pooled GroupKFold results are substantially more favorable than LODO results. When an entire dataset is held out, prediction error increases, differences among methods narrow, and performance is strongly affected by age-range mismatch and cohort heterogeneity. The benchmark provides common inputs, model settings, data splits, and analysis scripts so that future SPD matrix learning methods can be evaluated under the same external-validation protocol.
Jul 12, 2026cs.CV

Contrastive Joint-Embedding Prediction for Representation Learning in Structural MRI

Self-supervised learning offers a compelling approach for medical imaging, where labeled data are scarce and acquisition costs are high. We present COJEPA, a self-supervised framework for volumetric brain MRI that combines a joint-embedding predictive architecture (JEPA) with a contrastive loss (CO), targeting two complementary properties: local predictivity and global discriminability. The model is trained without labels on T1-weighted structural MRI from two cohorts (HCP-YA and AABC, N=2286N{=}2286, ages 22 to 90), extending I-JEPA to 3D with foreground-aware block masking, a hierarchical convolutional patch embedding, and world-space sinusoidal positional encodings. We evaluate all three objectives across zero-shot twin retrieval, brain tumor segmentation (BraTS 2024), and age regression (OpenBHB). COJEPA achieves the best monozygotic twin recall at rank@1 (0.84), the best finetuning age MAE (2.55 years on OpenBHB 3.0T), and matches CO on BraTS whole-tumor Dice, demonstrating that the combined objective yields representations that are simultaneously discriminative and locally structured.
Jul 7, 2026cs.LG

STST-JEPA: Shallow-Target Spatio-Temporal Joint Embedding Prediction Architecture For EEG Self-Supervised Learning

Brain age - the age inferred from a physiological recording - is an emerging biomarker whose deviation from chronological age tracks neurological and psychiatric burden, and EEG is an attractive substrate for it because it is cheap, portable, and temporally rich. Yet EEG brain-age models must contend with cross-site montage heterogeneity, small labelled cohorts, and dominant subject-level non-stationarity, and few EEG foundation models have been shown to deliver competitive age regression across the full pediatric to older adult range in which such a biomarker would actually be deployed. We introduce STST-JEPA, a self-supervised transformer for resting-state and task EEG, pretrained on 47,703 sessions spanning ages 5-81 from the brain.space and Healthy Brain Network (HBN) corpora. The model combines a latent-prediction objective - predicting masked-token representations against an EMA-of-tokenizer target - with an auxiliary signal-reconstruction term, applied to 30-second multi-channel windows under spatiotemporal block masks. A lightweight attentive probe trained on frozen pretrained embeddings achieves a best held-out-validation mean absolute error of 3.06 years (r = 0.924) for age regression on 3,367 sessions, against a predict-the-mean baseline of approximately 10 years MAE. With light task-specific finetuning of the model's final layers, the same pretrained encoder achieves rank-1 placements - with the model's native 30-second windows - on the public NeuralBench x brain.space EEG leaderboard for sex classification (balanced accuracy 0.911), age prediction (r = 0.749), and psychopathology composite regression (r = 0.215). We further show that the model's age-prediction residual is negatively correlated with cognitive efficiency over several tasks we examined.
Jun 25, 2026cs.CV

Modeling Local, Global, and Cross-Modal Context in Multimodal 3D MRI

Brain MRI poses a fundamental challenge for machine learning: models must learn from high-dimensional 3D data spanning multiple co-registered modalities, despite the limited sample sizes typical of neuroimaging studies relative to the diversity in anatomy, pathology, and acquisition conditions. While multimodal imaging provides complementary information critical for clinical interpretation, effectively integrating these signals remains difficult. We propose Multimodal Intra- and Cross-Context Vision Transformer (MICViT), a 3D vision transformer that explicitly models both modality-specific representations and cross-modal interactions across local and global contexts. Concretely, MICViT combines four attention mechanisms: modality-specific local and global attention for intra-modal feature learning, and cross-modal local and global attention to capture interactions between modalities. We evaluate MICViT on brain age prediction across three heterogeneous datasets (UK Biobank, n=41,404; SOOP, n=1,062; Cam-CAN, n=613) using multiple MRI modalities (e.g. T1, FLAIR, DWI, SWI). MICViT consistently outperforms state-of-the-art CNN and transformer baselines in 3D settings. Notably, it benefits more strongly from multimodal inputs, yielding larger performance gains as additional modalities are incorporated. These results demonstrate that explicitly modeling intra- and cross-modal interactions is key to unlocking the full potential of multimodal brain MRI, highlighting a promising direction for representation learning in neuroimaging.
May 16, 2026cs.AI

Brain Vascular Age Prediction Using Cerebral Blood Flow Velocity and Machine Learning Algorithms

Defining vascular age in terms of physiological function has become one focal point of the extensive studies to categorize and track chronological age. Transcranial Doppler (TCD) is a method by which cerebral blood flow velocity is measured along the major arteries feeding the human brain. This study aims to use features extracted from TCD to estimate chronological age and assess accelerated aging in subjects with various brain diseases. We predict subjects with various brain diseases to present with accelerated cerebrovascular aging when tested on various regression models trained by healthy subjects. 168 healthy subjects and 277 diseased subjects with bilateral TCD recordings of the middle cerebral artery were analyzed using the Morphological Analysis and Clustering of Intracranial Pressure (MOCAIP) algorithm. MOCAIP-generated features and heart rate variability features were used as input features for regression models to predict the brain vascular age. 66 subjects with acute stroke, 27 subjects with post stroke, 26 subjects with Alzheimer's disease, 23 subjects with mild cognitive impairment, and 135 established subjects were tested against the machine learning model to assess for accelerated cerebrovascular age. The trained model, on average, predicted healthy subjects' cerebrovascular age to be 3.69 years above their chronological age. Subjects with different disease conditions exhibited varying levels of age acceleration. The differences in healthy and diseased subjects' performances suggest that features generated using TCD may be relevant when evaluating accelerated cerebrovascular aging. Moreover, imbalanced datasets have been observed to affect the performance of machine-learning-based brain age prediction models.
Apr 17, 2026eess.IV

A Two-Stage Multi-Modal MRI Framework for Lifespan Brain Age Prediction

The accurate quantification of brain age from MRI has emerged as an important biomarker of brain health. However, existing approaches are often restricted to narrow age ranges and single-modality MRI data, limiting their capacity to capture the coordinated macro- and microstructural changes that unfold across the human lifespan. To address these limitations, we develop a multi-modal brain age framework to characterize the integrated evolution of brain morphology and white matter organization. Our model adopts a two-stage architecture, where modalities are processed independently and integrated via late fusion in both stages: first to estimate a probability distribution over six developmental stages, and then to predict age via probability-weighted stage-specialized experts. Experiments on nine datasets spanning fetal to elderly stages demonstrate competitive in-domain performance and out-of-domain generalization, with our method reducing MAE by 13% and 78% over existing baselines and multi-modal integration yielding 12-13% gains. Analysis of ADNI clinical groups further suggests the potential of the predicted brain age gap to characterize Alzheimer's-related brain aging.
Jun 18, 2025cs.LG

Federated Learning for MRI-based BrainAGE: a multicenter study on post-stroke functional outcome prediction

Objective:\textbf{Objective:} Brain-predicted age difference (BrainAGE) is a neuroimaging biomarker reflecting brain health. However, training robust BrainAGE models requires large datasets, often restricted by privacy concerns. This study evaluates the performance of federated learning (FL) for BrainAGE estimation in ischemic stroke patients treated with mechanical thrombectomy, and investigates its association with clinical phenotypes and functional outcomes. Methods:\textbf{Methods:} We used FLAIR brain images from 1674 stroke patients across 16 hospital centers. We implemented standard machine learning and deep learning models for BrainAGE estimates under three data management strategies: centralized learning (pooled data), FL (local training at each site), and single-site learning. We reported prediction errors and examined associations between BrainAGE and vascular risk factors (e.g., diabetes mellitus, hypertension, smoking), as well as functional outcomes at three months post-stroke. Logistic regression evaluated BrainAGE's predictive value for these outcomes, adjusting for age, sex, vascular risk factors, stroke severity, time between MRI and arterial puncture, prior intravenous thrombolysis, and recanalisation outcome. Results:\textbf{Results:} While centralized learning yielded the most accurate predictions, FL consistently outperformed single-site models. BrainAGE was significantly higher in patients with diabetes mellitus across all models. Comparisons between patients with good and poor functional outcomes, and multivariate predictions of these outcomes showed the significance of the association between BrainAGE and post-stroke recovery. Conclusion:\textbf{Conclusion:} FL enables accurate age predictions without data centralization. The strong association between BrainAGE, vascular risk factors, and post-stroke recovery highlights its potential for prognostic modeling in stroke care.
Dec 1, 2024eess.IV

Enhancing brain age estimation with structural MRI and synthesized cerebral blood volume maps

BrainAGE is a promising imaging-derived biomarker of neurobiological ageing and disease risk, yet current approaches rely predominantly on T1-weighted structural MRI, overlooking functional vascular changes that may precede tissue damage and cognitive decline. DeepCBV maps, synthesized from non-contrast MRI, offer a scalable alternative to contrast-enhanced perfusion imaging by capturing vascular information relevant to early neurodegeneration. We developed a multimodal BrainAGE framework that combines predictions from two separate three-dimensional convolutional neural networks: one trained only on structural MRI scans and another trained only on DeepCBV maps. Each model was trained and validated on 2851 scans from 13 open-source datasets and was evaluated for concordance with MCI and AD. The combined model achieved the most accurate brain age gap for CN controls, with a mean absolute error of 3.95 years, outperforming models trained on MRI or DeepCBV alone. Saliency maps revealed complementary modality contributions: MRI emphasized white matter and cortical atrophy, while DeepCBV highlighted vascular-rich and periventricular regions implicated in hypoperfusion and early cerebrovascular dysfunction, consistent with known patterns of normal ageing. Next, we observed that BrainAGE increased stepwise across diagnostic strata (CN < MCI < AD) and correlated with cognitive impairment. DeepCBV-based BrainAGE showed a particularly strong separation between stable versus progressive MCI, suggesting sensitivity to prodromal vascular changes that precede overt atrophy. Integrating structural MRI with deep learning-derived vascular measures substantially enhances BrainAGE estimation and improves sensitivity to MCI and AD progression, supporting its potential role in risk stratification, early detection and monitoring of therapeutic response.