mSPD-NN: A Geometrically Aware Neural Framework for Biomarker Discovery from Functional Connectomics Manifolds

Connectomics has emerged as a powerful tool in neuroimaging and has spurred recent advancements in statistical and machine learning methods for connectivity data. Despite connectomes inhabiting a matrix manifold, most analytical frameworks ignore the underlying data geometry. This is largely because simple operations, such as mean estimation, do not have easily computable closed-form solutions. We propose a geometrically aware neural framework for connectomes, i.e., the mSPD-NN, designed to estimate the geodesic mean of a collections of symmetric positive definite (SPD) matrices. The mSPD-NN is comprised of bilinear fully connected layers with tied weights and utilizes a novel loss function to optimize the matrix-normal equation arising from Fr\'echet mean estimation. Via experiments on synthetic data, we demonstrate the efficacy of our mSPD-NN against common alternatives for SPD mean estimation, providing competitive performance in terms of scalability and robustness to noise. We illustrate the real-world flexibility of the mSPD-NN in multiple experiments on rs-fMRI data and demonstrate that it uncovers stable biomarkers associated with subtle network differences among patients with ADHD-ASD comorbidities and healthy controls.

A Comparative Study of Data Augmentation Techniques for Deep Learning Based Emotion Recognition

Automated emotion recognition in speech is a long-standing problem. While early work on emotion recognition relied on hand-crafted features and simple classifiers, the field has now embraced end-to-end feature learning and classification using deep neural networks. In parallel to these models, researchers have proposed several data augmentation techniques to increase the size and variability of existing labeled datasets. Despite many seminal contributions in the field, we still have a poor understanding of the interplay between the network architecture and the choice of data augmentation. Moreover, only a handful of studies demonstrate the generalizability of a particular model across multiple datasets, which is a prerequisite for robust real-world performance. In this paper, we conduct a comprehensive evaluation of popular deep learning approaches for emotion recognition. To eliminate bias, we fix the model architectures and optimization hyperparameters using the VESUS dataset and then use repeated 5-fold cross validation to evaluate the performance on the IEMOCAP and CREMA-D datasets. Our results demonstrate that long-range dependencies in the speech signal are critical for emotion recognition and that speed/rate augmentation offers the most robust performance gain across models.

A Diffeomorphic Flow-based Variational Framework for Multi-speaker Emotion Conversion

This paper introduces a new framework for non-parallel emotion conversion in speech. Our framework is based on two key contributions. First, we propose a stochastic version of the popular CycleGAN model. Our modified loss function introduces a Kullback Leibler (KL) divergence term that aligns the source and target data distributions learned by the generators, thus overcoming the limitations of sample wise generation. By using a variational approximation to this stochastic loss function, we show that our KL divergence term can be implemented via a paired density discriminator. We term this new architecture a variational CycleGAN (VCGAN). Second, we model the prosodic features of target emotion as a smooth and learnable deformation of the source prosodic features. This approach provides implicit regularization that offers key advantages in terms of better range alignment to unseen and out of distribution speakers. We conduct rigorous experiments and comparative studies to demonstrate that our proposed framework is fairly robust with high performance against several state-of-the-art baselines.

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Prospective Learning: Back to the Future

Research on both natural intelligence (NI) and artificial intelligence (AI) generally assumes that the future resembles the past: intelligent agents or systems (what we call 'intelligence') observe and act on the world, then use this experience to act on future experiences of the same kind. We call this 'retrospective learning'. For example, an intelligence may see a set of pictures of objects, along with their names, and learn to name them. A retrospective learning intelligence would merely be able to name more pictures of the same objects. We argue that this is not what true intelligence is about. In many real world problems, both NIs and AIs will have to learn for an uncertain future. Both must update their internal models to be useful for future tasks, such as naming fundamentally new objects and using these objects effectively in a new context or to achieve previously unencountered goals. This ability to learn for the future we call 'prospective learning'. We articulate four relevant factors that jointly define prospective learning. Continual learning enables intelligences to remember those aspects of the past which it believes will be most useful in the future. Prospective constraints (including biases and priors) facilitate the intelligence finding general solutions that will be applicable to future problems. Curiosity motivates taking actions that inform future decision making, including in previously unmet situations. Causal estimation enables learning the structure of relations that guide choosing actions for specific outcomes, even when the specific action-outcome contingencies have never been observed before. We argue that a paradigm shift from retrospective to prospective learning will enable the communities that study intelligence to unite and overcome existing bottlenecks to more effectively explain, augment, and engineer intelligences.

A Deep-Bayesian Framework for Adaptive Speech Duration Modification

We propose the first method to adaptively modify the duration of a given speech signal. Our approach uses a Bayesian framework to define a latent attention map that links frames of the input and target utterances. We train a masked convolutional encoder-decoder network to produce this attention map via a stochastic version of the mean absolute error loss function; our model also predicts the length of the target speech signal using the encoder embeddings. The predicted length determines the number of steps for the decoder operation. During inference, we generate the attention map as a proxy for the similarity matrix between the given input speech and an unknown target speech signal. Using this similarity matrix, we compute a warping path of alignment between the two signals. Our experiments demonstrate that this adaptive framework produces similar results to dynamic time warping, which relies on a known target signal, on both voice conversion and emotion conversion tasks. We also show that our technique results in a high quality of generated speech that is on par with state-of-the-art vocoders.

A Matrix Autoencoder Framework to Align the Functional and Structural Connectivity Manifolds as Guided by Behavioral Phenotypes

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.

G-MIND: An End-to-End Multimodal Imaging-Genetics Framework for Biomarker Identification and Disease Classification

We propose a novel deep neural network architecture to integrate imaging and genetics data, as guided by diagnosis, that provides interpretable biomarkers. Our model consists of an encoder, a decoder and a classifier. The encoder learns a non-linear subspace shared between the input data modalities. The classifier and the decoder act as regularizers to ensure that the low-dimensional encoding captures predictive differences between patients and controls. We use a learnable dropout layer to extract interpretable biomarkers from the data, and our unique training strategy can easily accommodate missing data modalities across subjects. We have evaluated our model on a population study of schizophrenia that includes two functional MRI (fMRI) paradigms and Single Nucleotide Polymorphism (SNP) data. Using 10-fold cross validation, we demonstrate that our model achieves better classification accuracy than baseline methods, and that this performance generalizes to a second dataset collected at a different site. In an exploratory analysis we further show that the biomarkers identified by our model are closely associated with the well-documented deficits in schizophrenia.

A Multi-Task Deep Learning Framework to Localize the Eloquent Cortex in Brain Tumor Patients Using Dynamic Functional Connectivity

We present a novel deep learning framework that uses dynamic functional connectivity to simultaneously localize the language and motor areas of the eloquent cortex in brain tumor patients. Our method leverages convolutional layers to extract graph-based features from the dynamic connectivity matrices and a long-short term memory (LSTM) attention network to weight the relevant time points during classification. The final stage of our model employs multi-task learning to identify different eloquent subsystems. Our unique training strategy finds a shared representation between the cognitive networks of interest, which enables us to handle missing patient data. We evaluate our method on resting-state fMRI data from 56 brain tumor patients while using task fMRI activations as surrogate ground-truth labels for training and testing. Our model achieves higher localization accuracies than conventional deep learning approaches and can identify bilateral language areas even when trained on left-hemisphere lateralized cases. Hence, our method may ultimately be useful for preoperative mapping in tumor patients.

Deep sr-DDL: Deep Structurally Regularized Dynamic Dictionary Learning to Integrate Multimodal and Dynamic Functional Connectomics data for Multidimensional Clinical Characterizations

We propose a novel integrated framework that jointly models complementary information from resting-state functional MRI (rs-fMRI) connectivity and diffusion tensor imaging (DTI) tractography to extract biomarkers of brain connectivity predictive of behavior. Our framework couples a generative model of the connectomics data with a deep network that predicts behavioral scores. The generative component 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 subject-specific loadings. We use the DTI tractography to regularize this matrix factorization and learn anatomically informed functional connectivity profiles. The deep component of our framework is an LSTM-ANN block, which uses the temporal evolution of the subject-specific sr-DDL loadings to predict multidimensional clinical characterizations. Our joint optimization strategy collectively estimates the basis networks, the subject-specific time-varying loadings, and the neural network weights. We validate our framework on a dataset of neurotypical individuals from the Human Connectome Project (HCP) database to map to cognition and on a separate multi-score prediction task on individuals diagnosed with Autism Spectrum Disorder (ASD) in a five-fold cross validation setting. Our hybrid model outperforms several state-of-the-art approaches at clinical outcome prediction and learns interpretable multimodal neural signatures of brain organization.