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.

Graph neural networks (GNN) are an effective framework that exploit inter-relationships within graph-structured data for learning. Principal component analysis (PCA) involves the projection of data on the eigenspace of the covariance matrix and draws similarities with the graph convolutional filters in GNNs. Motivated by this observation, we study a GNN architecture, called coVariance neural network (VNN), that operates on sample covariance matrices as graphs. We theoretically establish the stability of VNNs to perturbations in the covariance matrix, thus, implying an advantage over standard PCA-based data analysis approaches that are prone to instability due to principal components associated with close eigenvalues. Our experiments on real-world datasets validate our theoretical results and show that VNN performance is indeed more stable than PCA-based statistical approaches. Moreover, our experiments on multi-resolution datasets also demonstrate that VNNs are amenable to transferability of performance over covariance matrices of different dimensions; a feature that is infeasible for PCA-based approaches.

CoVariance Neural Networks (VNNs) perform graph convolutions on the empirical covariance matrix of signals defined over finite-dimensional Hilbert spaces, motivated by robustness and transferability properties. Yet, little is known about how these arguments extend to infinite-dimensional Hilbert spaces. In this work, we take a first step by introducing a novel convolutional learning framework for signals defined over infinite-dimensional Hilbert spaces, centered on the (empirical) covariance operator. We constructively define Hilbert coVariance Filters (HVFs) and design Hilbert coVariance Networks (HVNs) as stacks of HVF filterbanks with nonlinear activations. We propose a principled discretization procedure, and we prove that empirical HVFs can recover the Functional PCA (FPCA) of the filtered signals. We then describe the versatility of our framework with examples ranging from multivariate real-valued functions to reproducing kernel Hilbert spaces. Finally, we validate HVNs on both synthetic and real-world time-series classification tasks, showing robust performance compared to MLP and FPCA-based classifiers.

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.

Graph neural networks (GNN) are an effective framework that exploit inter-relationships within graph-structured data for learning. Principal component analysis (PCA) involves the projection of data on the eigenspace of the covariance matrix and draws similarities with the graph convolutional filters in GNNs. Motivated by this observation, we study a GNN architecture, called coVariance neural network (VNN), that operates on sample covariance matrices as graphs. We theoretically establish the stability of VNNs to perturbations in the covariance matrix, thus, implying an advantage over standard PCA-based data analysis approaches that are prone to instability due to principal components associated with close eigenvalues. Our experiments on real-world datasets validate our theoretical results and show that VNN performance is indeed more stable than PCA-based statistical approaches.

Graph neural networks (GNN) are an effective framework that exploit inter-relationships within graph-structured data for learning. Principal component analysis (PCA) involves the projection of data on the eigenspace of the covariance matrix and draws similarities with the graph convolutional filters in GNNs. Motivated by this observation, we study a GNN architecture, called coVariance neural network (VNN), that operates on sample covariance matrices as graphs. We theoretically establish the stability of VNNs to perturbations in the covariance matrix, thus, implying an advantage over standard PCA-based data analysis approaches that are prone to instability due to principal components associated with close eigenvalues. Our experiments on real-world datasets validate our theoretical results and show that VNN performance is indeed more stable than PCA-based statistical approaches. Moreover, our experiments on multi-resolution datasets also demonstrate that VNNs are amenable to transferability of performance over covariance matrices of different dimensions; a feature that is infeasible for PCA-based approaches.