Stewart Mostofsky

Niharika Shimona D'Souza, Mary Beth Nebel, Deana Crocetti et al.

We propose a novel matrix autoencoder to map functional connectomes from resting state fMRI (rs-fMRI) to structural connectomes from Diffusion Tensor Imaging (DTI), as guided by subject-level phenotypic measures. Our specialized autoencoder infers a low dimensional manifold embedding for the rs-fMRI correlation matrices that mimics a canonical outer-product decomposition. The embedding is simultaneously used to reconstruct DTI tractography matrices via a second manifold alignment decoder and to predict inter-subject phenotypic variability via an artificial neural network. We validate our framework on a dataset of 275 healthy individuals from the Human Connectome Project database and on a second clinical dataset consisting of 57 subjects with Autism Spectrum Disorder. We demonstrate that the model reliably recovers structural connectivity patterns across individuals, while robustly extracting predictive and interpretable brain biomarkers in a cross-validated setting. Finally, our framework outperforms several baselines at predicting behavioral phenotypes in both real-world datasets.

Niharika Shimona D'Souza, Mary Beth Nebel, Deana Crocetti et al.

We propose an integrated deep-generative framework, that jointly models complementary information from resting-state functional MRI (rs-fMRI) connectivity and diffusion tensor imaging (DTI) tractography to extract predictive biomarkers of a disease. The generative part of our framework is a structurally-regularized Dynamic Dictionary Learning (sr-DDL) model that decomposes the dynamic rs-fMRI correlation matrices into a collection of shared basis networks and time varying patient-specific loadings. This matrix factorization is guided by the DTI tractography matrices to learn anatomically informed connectivity profiles. The deep part of our framework is an LSTM-ANN block, which models the temporal evolution of the patient sr-DDL loadings to predict multidimensional clinical severity. Our coupled optimization procedure collectively estimates the basis networks, the patient-specific dynamic loadings, and the neural network weights. We validate our framework on a multi-score prediction task in 57 patients diagnosed with Autism Spectrum Disorder (ASD). Our hybrid model outperforms state-of-the-art baselines in a five-fold cross validated setting and extracts interpretable multimodal neural signatures of brain dysfunction in ASD.

Niharika Shimona D'Souza, Mary Beth Nebel, Nicholas Wymbs et al.

We propose a unified optimization framework that combines neural networks with dictionary learning to model complex interactions between resting state functional MRI and behavioral data. The dictionary learning objective decomposes patient correlation matrices into a collection of shared basis networks and subject-specific loadings. These subject-specific features are simultaneously input into a neural network that predicts multidimensional clinical information. Our novel optimization framework combines the gradient information from the neural network with that of a conventional matrix factorization objective. This procedure collectively estimates the basis networks, subject loadings, and neural network weights most informative of clinical severity. We evaluate our combined model on a multi-score prediction task using 52 patients diagnosed with Autism Spectrum Disorder (ASD). Our integrated framework outperforms state-of-the-art methods in a ten-fold cross validated setting to predict three different measures of clinical severity.

Niharika Shimona D'Souza, Mary Beth Nebel, Nicholas Wymbs et al.

The problem of linking functional connectomics to behavior is extremely challenging due to the complex interactions between the two distinct, but related, data domains. We propose a coupled manifold optimization framework which projects fMRI data onto a low dimensional matrix manifold common to the cohort. The patient specific loadings simultaneously map onto a behavioral measure of interest via a second, non-linear, manifold. By leveraging the kernel trick, we can optimize over a potentially infinite dimensional space without explicitly computing the embeddings. As opposed to conventional manifold learning, which assumes a fixed input representation, our framework directly optimizes for embedding directions that predict behavior. Our optimization algorithm combines proximal gradient descent with the trust region method, which has good convergence guarantees. We validate our framework on resting state fMRI from fifty-eight patients with Autism Spectrum Disorder using three distinct measures of clinical severity. Our method outperforms traditional representation learning techniques in a cross validated setting, thus demonstrating the predictive power of our coupled objective.