Multiscale Neuroimaging Features for the Identification of Medication Class and Non-Responders in Mood Disorder Treatment

In the clinical treatment of mood disorders, the complex behavioral symptoms presented by patients and variability of patient response to particular medication classes can create difficulties in providing fast and reliable treatment when standard diagnostic and prescription methods are used. Increasingly, the incorporation of physiological information such as neuroimaging scans and derivatives into the clinical process promises to alleviate some of the uncertainty surrounding this process. Particularly, if neural features can help to identify patients who may not respond to standard courses of anti-depressants or mood stabilizers, clinicians may elect to avoid lengthy and side-effect-laden treatments and seek out a different, more effective course that might otherwise not have been under consideration. Previously, approaches for the derivation of relevant neuroimaging features work at only one scale in the data, potentially limiting the depth of information available for clinical decision support. In this work, we show that the utilization of multi spatial scale neuroimaging features - particularly resting state functional networks and functional network connectivity measures - provide a rich and robust basis for the identification of relevant medication class and non-responders in the treatment of mood disorders. We demonstrate that the generated features, along with a novel approach for fast and automated feature selection, can support high accuracy rates in the identification of medication class and non-responders as well as the identification of novel, multi-scale biomarkers.

Low-Rank Learning by Design: the Role of Network Architecture and Activation Linearity in Gradient Rank Collapse

Our understanding of learning dynamics of deep neural networks (DNNs) remains incomplete. Recent research has begun to uncover the mathematical principles underlying these networks, including the phenomenon of "Neural Collapse", where linear classifiers within DNNs converge to specific geometrical structures during late-stage training. However, the role of geometric constraints in learning extends beyond this terminal phase. For instance, gradients in fully-connected layers naturally develop a low-rank structure due to the accumulation of rank-one outer products over a training batch. Despite the attention given to methods that exploit this structure for memory saving or regularization, the emergence of low-rank learning as an inherent aspect of certain DNN architectures has been under-explored. In this paper, we conduct a comprehensive study of gradient rank in DNNs, examining how architectural choices and structure of the data effect gradient rank bounds. Our theoretical analysis provides these bounds for training fully-connected, recurrent, and convolutional neural networks. We also demonstrate, both theoretically and empirically, how design choices like activation function linearity, bottleneck layer introduction, convolutional stride, and sequence truncation influence these bounds. Our findings not only contribute to the understanding of learning dynamics in DNNs, but also provide practical guidance for deep learning engineers to make informed design decisions.

Improving age prediction: Utilizing LSTM-based dynamic forecasting for data augmentation in multivariate time series analysis

The high dimensionality and complexity of neuroimaging data necessitate large datasets to develop robust and high-performing deep learning models. However, the neuroimaging field is notably hampered by the scarcity of such datasets. In this work, we proposed a data augmentation and validation framework that utilizes dynamic forecasting with Long Short-Term Memory (LSTM) networks to enrich datasets. We extended multivariate time series data by predicting the time courses of independent component networks (ICNs) in both one-step and recursive configurations. The effectiveness of these augmented datasets was then compared with the original data using various deep learning models designed for chronological age prediction tasks. The results suggest that our approach improves model performance, providing a robust solution to overcome the challenges presented by the limited size of neuroimaging datasets.

Constrained Independent Vector Analysis with Reference for Multi-Subject fMRI Analysis

Independent component analysis (ICA) is now a widely used solution for the analysis of multi-subject functional magnetic resonance imaging (fMRI) data. Independent vector analysis (IVA) generalizes ICA to multiple datasets, i.e., to multi-subject data, and in addition to higher-order statistical information in ICA, it leverages the statistical dependence across the datasets as an additional type of statistical diversity. As such, it preserves variability in the estimation of single-subject maps but its performance might suffer when the number of datasets increases. Constrained IVA is an effective way to bypass computational issues and improve the quality of separation by incorporating available prior information. Existing constrained IVA approaches often rely on user-defined threshold values to define the constraints. However, an improperly selected threshold can have a negative impact on the final results. This paper proposes two novel methods for constrained IVA: one using an adaptive-reverse scheme to select variable thresholds for the constraints and a second one based on a threshold-free formulation by leveraging the unique structure of IVA. We demonstrate that our solutions provide an attractive solution to multi-subject fMRI analysis both by simulations and through analysis of resting state fMRI data collected from 98 subjects -- the highest number of subjects ever used by IVA algorithms. Our results show that both proposed approaches obtain significantly better separation quality and model match while providing computationally efficient and highly reproducible solutions.

Predictive Sparse Manifold Transform

We present Predictive Sparse Manifold Transform (PSMT), a minimalistic, interpretable and biologically plausible framework for learning and predicting natural dynamics. PSMT incorporates two layers where the first sparse coding layer represents the input sequence as sparse coefficients over an overcomplete dictionary and the second manifold learning layer learns a geometric embedding space that captures topological similarity and dynamic temporal linearity in sparse coefficients. We apply PSMT on a natural video dataset and evaluate the reconstruction performance with respect to contextual variability, the number of sparse coding basis functions and training samples. We then interpret the dynamic topological organization in the embedding space. We next utilize PSMT to predict future frames compared with two baseline methods with a static embedding space. We demonstrate that PSMT with a dynamic embedding space can achieve better prediction performance compared to static baselines. Our work establishes that PSMT is an efficient unsupervised generative framework for prediction of future visual stimuli.

Looking deeper into interpretable deep learning in neuroimaging: a comprehensive survey

Deep learning (DL) models have been popular due to their ability to learn directly from the raw data in an end-to-end paradigm, alleviating the concern of a separate error-prone feature extraction phase. Recent DL-based neuroimaging studies have also witnessed a noticeable performance advancement over traditional machine learning algorithms. But the challenges of deep learning models still exist because of the lack of transparency in these models for their successful deployment in real-world applications. In recent years, Explainable AI (XAI) has undergone a surge of developments mainly to get intuitions of how the models reached the decisions, which is essential for safety-critical domains such as healthcare, finance, and law enforcement agencies. While the interpretability domain is advancing noticeably, researchers are still unclear about what aspect of model learning a post hoc method reveals and how to validate its reliability. This paper comprehensively reviews interpretable deep learning models in the neuroimaging domain. Firstly, we summarize the current status of interpretability resources in general, focusing on the progression of methods, associated challenges, and opinions. Secondly, we discuss how multiple recent neuroimaging studies leveraged model interpretability to capture anatomical and functional brain alterations most relevant to model predictions. Finally, we discuss the limitations of the current practices and offer some valuable insights and guidance on how we can steer our future research directions to make deep learning models substantially interpretable and thus advance scientific understanding of brain disorders.

New Interpretable Patterns and Discriminative Features from Brain Functional Network Connectivity Using Dictionary Learning

Independent component analysis (ICA) of multi-subject functional magnetic resonance imaging (fMRI) data has proven useful in providing a fully multivariate summary that can be used for multiple purposes. ICA can identify patterns that can discriminate between healthy controls (HC) and patients with various mental disorders such as schizophrenia (Sz). Temporal functional network connectivity (tFNC) obtained from ICA can effectively explain the interactions between brain networks. On the other hand, dictionary learning (DL) enables the discovery of hidden information in data using learnable basis signals through the use of sparsity. In this paper, we present a new method that leverages ICA and DL for the identification of directly interpretable patterns to discriminate between the HC and Sz groups. We use multi-subject resting-state fMRI data from $358$ subjects and form subject-specific tFNC feature vectors from ICA results. Then, we learn sparse representations of the tFNCs and introduce a new set of sparse features as well as new interpretable patterns from the learned atoms. Our experimental results show that the new representation not only leads to effective classification between HC and Sz groups using sparse features, but can also identify new interpretable patterns from the learned atoms that can help understand the complexities of mental diseases such as schizophrenia.

Self-supervised multimodal neuroimaging yields predictive representations for a spectrum of Alzheimer's phenotypes

Recent neuroimaging studies that focus on predicting brain disorders via modern machine learning approaches commonly include a single modality and rely on supervised over-parameterized models.However, a single modality provides only a limited view of the highly complex brain. Critically, supervised models in clinical settings lack accurate diagnostic labels for training. Coarse labels do not capture the long-tailed spectrum of brain disorder phenotypes, which leads to a loss of generalizability of the model that makes them less useful in diagnostic settings. This work presents a novel multi-scale coordinated framework for learning multiple representations from multimodal neuroimaging data. We propose a general taxonomy of informative inductive biases to capture unique and joint information in multimodal self-supervised fusion. The taxonomy forms a family of decoder-free models with reduced computational complexity and a propensity to capture multi-scale relationships between local and global representations of the multimodal inputs. We conduct a comprehensive evaluation of the taxonomy using functional and structural magnetic resonance imaging (MRI) data across a spectrum of Alzheimer's disease phenotypes and show that self-supervised models reveal disorder-relevant brain regions and multimodal links without access to the labels during pre-training. The proposed multimodal self-supervised learning yields representations with improved classification performance for both modalities. The concomitant rich and flexible unsupervised deep learning framework captures complex multimodal relationships and provides predictive performance that meets or exceeds that of a more narrow supervised classification analysis. We present elaborate quantitative evidence of how this framework can significantly advance our search for missing links in complex brain disorders.

Dynamic Topological Data Analysis for Brain Networks via Wasserstein Graph Clustering

We present the novel Wasserstein graph clustering for dynamically changing graphs. The Wasserstein clustering penalizes the topological discrepancy between graphs. The Wasserstein clustering is shown to outperform the widely used k-means clustering. The method applied in more accurate determination of the state spaces of dynamically changing functional brain networks.

Dynamic Persistent Homology for Brain Networks via Wasserstein Graph Clustering

We present the novel Wasserstein graph clustering for dynamically changing graphs. The Wasserstein clustering penalizes the topological discrepancy between graphs. The Wasserstein clustering is shown to outperform the widely used k-means clustering. The method applied in more accurate determination of the state spaces of dynamically changing functional brain networks.