The brain age is a key indicator of brain health. While electroencephalography (EEG) is a practical tool for this task, existing models struggle with the common challenge of imperfect medical data, such as learning a ``normal'' baseline from weakly supervised, healthy-only cohorts. This is a critical anomaly detection task for identifying disease, but standard models are often black boxes lacking an interpretable structure. We propose EVA-Net, a novel framework that recasts brain age as an interpretable anomaly detection problem. EVA-Net uses an efficient, sparsified-attention Transformer to model long EEG sequences. To handle noise and variability in imperfect data, it employs a Variational Information Bottleneck to learn a robust, compressed representation. For interpretability, this representation is aligned to a continuous prototype network that explicitly learns the normative healthy aging manifold. Trained on 1297 healthy subjects, EVA-Net achieves state-of-the-art accuracy. We validated its anomaly detection capabilities on an unseen cohort of 27 MCI and AD patients. This pathological group showed significantly higher brain-age gaps and a novel Prototype Alignment Error, confirming their deviation from the healthy manifold. EVA-Net provides an interpretable framework for healthcare intelligence using imperfect medical data.

Accurate estimation of biological brain age from three dimensional (3D) T$_1$-weighted magnetic resonance imaging (MRI) is a critical imaging biomarker for identifying accelerated aging associated with neurodegenerative diseases. Effective brain age prediction necessitates training 3D models to leverage comprehensive insights from volumetric MRI scans, thereby fully capturing spatial anatomical context. However, optimizing deep 3D models remains challenging due to problems such as vanishing gradients. Furthermore, brain structural patterns differ significantly between sexes, which impacts aging trajectories and vulnerability to neurodegenerative diseases, thereby making sex classification crucial for enhancing the accuracy and generalizability of predictive models. To address these challenges, we propose a Deeply Supervised Multitask Autoencoder (DSMT-AE) framework for brain age estimation. DSMT-AE employs deep supervision, which involves applying supervisory signals at intermediate layers during training, to stabilize model optimization, and multitask learning to enhance feature representation. Specifically, our framework simultaneously optimizes brain age prediction alongside auxiliary tasks of sex classification and image reconstruction, thus effectively capturing anatomical and demographic variability to improve prediction accuracy. We extensively evaluate DSMT-AE on the Open Brain Health Benchmark (OpenBHB) dataset, the largest multisite neuroimaging cohort combining ten publicly available datasets. The results demonstrate that DSMT-AE achieves state-of-the-art performance and robustness across age and sex subgroups. Additionally, our ablation study confirms that each proposed component substantially contributes to the improved predictive accuracy and robustness of the overall architecture.

Age prediction using brain imaging, such as MRIs, has achieved promising results, with several studies identifying the model's residual as a potential biomarker for chronic disease states. In this study, we developed a brain age predictive model using a dataset of 1,220 U.S. veterans (18--80 years) and convolutional neural networks (CNNs) trained on two-dimensional slices of axial T2-weighted fast spin-echo and T2-weighted fluid attenuated inversion recovery MRI images. The model, incorporating a degree-3 polynomial ensemble, achieved an $R^{2}$ of 0.816 on the testing set. Images were acquired at the level of the anterior commissure and the frontal horns of the lateral ventricles. Residual analysis was performed to assess its potential as a biomarker for five ICD-coded conditions: hypertension (HTN), diabetes mellitus (DM), mild traumatic brain injury (mTBI), illicit substance abuse/dependence (SAD), and alcohol abuse/dependence (AAD). Residuals grouped by the number of ICD-coded conditions demonstrated different trends that were statistically significant ($p = 0.002$), suggesting a relationship between disease states and predicted brain age. This association was particularly pronounced in patients over 49 years, where negative residuals (indicating advanced brain aging) correlated with the presence of multiple ICD codes. These findings support the potential of residuals as biomarkers for detecting latent health conditions.

The increasing global aging population necessitates improved methods to assess brain aging and its related neurodegenerative changes. Brain Age Gap Estimation (BrainAGE) offers a neuroimaging biomarker for understanding these changes by predicting brain age from MRI scans. Current approaches primarily use T1-weighted magnetic resonance imaging (T1w MRI) data, capturing only structural brain information. To address this limitation, AI-generated Cerebral Blood Volume (AICBV) data, synthesized from non-contrast MRI scans, offers functional insights by revealing subtle blood-tissue contrasts otherwise undetectable in standard imaging. We integrated AICBV with T1w MRI to predict brain age, combining both structural and functional metrics. We developed a deep learning model using a VGG-based architecture for both modalities and combined their predictions using linear regression. Our model achieved a mean absolute error (MAE) of 3.95 years and an $R^2$ of 0.943 on the test set ($n = 288$), outperforming existing models trained on similar data. We have further created gradient-based class activation maps (Grad-CAM) to visualize the regions of the brain that most influenced the model's predictions, providing interpretable insights into the structural and functional contributors to brain aging.

In the field of neuroimaging, accurate brain age prediction is pivotal for uncovering the complexities of brain aging and pinpointing early indicators of neurodegenerative conditions. Recent advancements in self-supervised learning, particularly in contrastive learning, have demonstrated greater robustness when dealing with complex datasets. However, current approaches often fall short in generalizing across non-uniformly distributed data, prevalent in medical imaging scenarios. To bridge this gap, we introduce a novel contrastive loss that adapts dynamically during the training process, focusing on the localized neighborhoods of samples. Moreover, we expand beyond traditional structural features by incorporating brain stiffness--a mechanical property previously underexplored yet promising due to its sensitivity to age-related changes. This work presents the first application of self-supervised learning to brain mechanical properties, using compiled stiffness maps from various clinical studies to predict brain age. Our approach, featuring dynamic localized loss, consistently outperforms existing state-of-the-art methods, demonstrating superior performance and laying the way for new directions in brain aging research.

The integration of diverse clinical modalities such as medical imaging and the tabular data obtained by the patients' Electronic Health Records (EHRs) is a crucial aspect of modern healthcare. The integrative analysis of multiple sources can provide a comprehensive understanding of a patient's condition and can enhance diagnoses and treatment decisions. Deep Neural Networks (DNNs) consistently showcase outstanding performance in a wide range of multimodal tasks in the medical domain. However, the complex endeavor of effectively merging medical imaging with clinical, demographic and genetic information represented as numerical tabular data remains a highly active and ongoing research pursuit. We present a novel framework based on hypernetworks to fuse clinical imaging and tabular data by conditioning the image processing on the EHR's values and measurements. This approach aims to leverage the complementary information present in these modalities to enhance the accuracy of various medical applications. We demonstrate the strength and the generality of our method on two different brain Magnetic Resonance Imaging (MRI) analysis tasks, namely, brain age prediction conditioned by subject's sex, and multiclass Alzheimer's Disease (AD) classification conditioned by tabular data. We show that our framework outperforms both single-modality models and state-of-the-art MRI-tabular data fusion methods. The code, enclosed to this manuscript will be made publicly available.

Brain age is the estimate of biological age derived from neuroimaging datasets using machine learning algorithms. Increasing brain age with respect to chronological age can reflect increased vulnerability to neurodegeneration and cognitive decline. In this paper, we study NeuroVNN, based on coVariance neural networks, as a paradigm for foundation model for the brain age prediction application. NeuroVNN is pre-trained as a regression model on healthy population to predict chronological age using cortical thickness features and fine-tuned to estimate brain age in different neurological contexts. Importantly, NeuroVNN adds anatomical interpretability to brain age and has a `scale-free' characteristic that allows its transference to datasets curated according to any arbitrary brain atlas. Our results demonstrate that NeuroVNN can extract biologically plausible brain age estimates in different populations, as well as transfer successfully to datasets of dimensionalities distinct from that for the dataset used to train NeuroVNN.

In computational neuroscience, there has been an increased interest in developing machine learning algorithms that leverage brain imaging data to provide estimates of "brain age" for an individual. Importantly, the discordance between brain age and chronological age (referred to as "brain age gap") can capture accelerated aging due to adverse health conditions and therefore, can reflect increased vulnerability towards neurological disease or cognitive impairments. However, widespread adoption of brain age for clinical decision support has been hindered due to lack of transparency and methodological justifications in most existing brain age prediction algorithms. In this paper, we leverage coVariance neural networks (VNN) to propose an explanation-driven and anatomically interpretable framework for brain age prediction using cortical thickness features. Specifically, our brain age prediction framework extends beyond the coarse metric of brain age gap in Alzheimer's disease (AD) and we make two important observations: (i) VNNs can assign anatomical interpretability to elevated brain age gap in AD by identifying contributing brain regions, (ii) the interpretability offered by VNNs is contingent on their ability to exploit specific eigenvectors of the anatomical covariance matrix. Together, these observations facilitate an explainable and anatomically interpretable perspective to the task of brain age prediction.