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Vince D. Calhoun

Vince D. Calhoun contributes to research discovery and scholarly infrastructure.

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Published work

14 published item(s)

preprint2026arXiv

Isolating Nonlinear Independent Sources in fMRI with $β$-TCVAE Models

Learning meaningful latent representations from nonlinear fMRI data remains a fundamental challenge in neuroimaging analysis. Traditional independent component analysis, widely used due to its ability to estimate interpretable functional brain networks, relies on a linear mixing assumption for latent sources, limiting its ability to capture the inherently nonlinear and complex organization of brain dynamics. More recently, deep representation learning methods have emerged as promising alternatives for modeling nonlinear latent structure. However, many of these approaches have been evaluated primarily on simulated datasets or natural image benchmarks, with comparatively limited validation on real-world neuroimaging data such as fMRI. In this work, we are motivated by the $β$-TCVAE (Total Correlation Variational Autoencoder), a refinement of the $β$-VAE framework for learning latent representations without introducing additional hyperparameters during training. We adapt and modify this model to fMRI data for nonlinear source disentanglement, aiming to separate mixed spatial and temporal brain signals into interpretable components. We show that the $β$-TCVAE framework can recover meaningful nonlinear spatial components with biological relevance, including well-established intrinsic connectivity networks such as the default mode network. Furthermore, we evaluate the learned representations using functional network connectivity, showing that the latent structure captures coherent and interpretable brain organization patterns. This study provides a pilot investigation that bridges nonlinear representation learning and fMRI analysis.

preprint2025arXiv

An interpretable generative multimodal neuroimaging-genomics framework for decoding Alzheimer's disease

\textbf{Objective:} Alzheimer's disease (AD) is the most prevalent form of dementia worldwide, encompassing a prodromal stage known as Mild Cognitive Impairment (MCI), where patients may either progress to AD or remain stable. The objective of the work was to capture structural and functional modulations of brain structure and function relying on multimodal MRI data and Single Nucleotide Polymorphisms, also in case of missing views, with the twofold goal of classifying AD patients versus healthy controls and detecting MCI converters. % in two distinct tasks, dealing with also missing data.\\ \textbf{Approach:} We propose a multimodal DL-based classification framework where a generative module employing Cycle Generative Adversarial Networks was introduced in the latent space for imputing missing data (a common issue of multimodal approaches). Explainable AI method was then used to extract input features' relevance allowing for post-hoc validation and enhancing the interpretability of the learned representations. \textbf{Main results:} Experimental results on two tasks, AD detection and MCI conversion, showed that our framework reached competitive performance in the state-of-the-art with an accuracy of $0.926\pm0.02$ and $0.711\pm0.01$ in the two tasks, respectively. The interpretability analysis revealed gray matter modulations in cortical and subcortical brain areas typically associated with AD. Moreover, impairments in sensory-motor and visual resting state networks along the disease continuum, as well as genetic mutations defining biological processes linked to endocytosis, amyloid-beta, and cholesterol, were identified. \textbf{Significance:} Our integrative and interpretable DL approach shows promising performance for AD detection and MCI prediction while shedding light on important biological insights.

preprint2025arXiv

Deep Deterministic Nonlinear ICA via Total Correlation Minimization with Matrix-Based Entropy Functional

Blind source separation, particularly through independent component analysis (ICA), is widely utilized across various signal processing domains for disentangling underlying components from observed mixed signals, owing to its fully data-driven nature that minimizes reliance on prior assumptions. However, conventional ICA methods rely on an assumption of linear mixing, limiting their ability to capture complex nonlinear relationships and to maintain robustness in noisy environments. In this work, we present deep deterministic nonlinear independent component analysis (DDICA), a novel deep neural network-based framework designed to address these limitations. DDICA leverages a matrix-based entropy function to directly optimize the independence criterion via stochastic gradient descent, bypassing the need for variational approximations or adversarial schemes. This results in a streamlined training process and improved resilience to noise. We validated the effectiveness and generalizability of DDICA across a range of applications, including simulated signal mixtures, hyperspectral image unmixing, modeling of primary visual receptive fields, and resting-state functional magnetic resonance imaging (fMRI) data analysis. Experimental results demonstrate that DDICA effectively separates independent components with high accuracy across a range of applications. These findings suggest that DDICA offers a robust and versatile solution for blind source separation in diverse signal processing tasks.

preprint2022arXiv

An AO-ADMM approach to constraining PARAFAC2 on all modes

Analyzing multi-way measurements with variations across one mode of the dataset is a challenge in various fields including data mining, neuroscience and chemometrics. For example, measurements may evolve over time or have unaligned time profiles. The PARAFAC2 model has been successfully used to analyze such data by allowing the underlying factor matrices in one mode (i.e., the evolving mode) to change across slices. The traditional approach to fit a PARAFAC2 model is to use an alternating least squares-based algorithm, which handles the constant cross-product constraint of the PARAFAC2 model by implicitly estimating the evolving factor matrices. This approach makes imposing regularization on these factor matrices challenging. There is currently no algorithm to flexibly impose such regularization with general penalty functions and hard constraints. In order to address this challenge and to avoid the implicit estimation, in this paper, we propose an algorithm for fitting PARAFAC2 based on alternating optimization with the alternating direction method of multipliers (AO-ADMM). With numerical experiments on simulated data, we show that the proposed PARAFAC2 AO-ADMM approach allows for flexible constraints, recovers the underlying patterns accurately, and is computationally efficient compared to the state-of-the-art. We also apply our model to two real-world datasets from neuroscience and chemometrics, and show that constraining the evolving mode improves the interpretability of the extracted patterns.

preprint2022arXiv

On self-supervised multi-modal representation learning: An application to Alzheimer's disease

Introspection of deep supervised predictive models trained on functional and structural brain imaging may uncover novel markers of Alzheimer's disease (AD). However, supervised training is prone to learning from spurious features (shortcut learning) impairing its value in the discovery process. Deep unsupervised and, recently, contrastive self-supervised approaches, not biased to classification, are better candidates for the task. Their multimodal options specifically offer additional regularization via modality interactions. In this paper, we introduce a way to exhaustively consider multimodal architectures for contrastive self-supervised fusion of fMRI and MRI of AD patients and controls. We show that this multimodal fusion results in representations that improve the results of the downstream classification for both modalities. We investigate the fused self-supervised features projected into the brain space and introduce a numerically stable way to do so.

preprint2022arXiv

Peering Beyond the Gradient Veil with Distributed Auto Differentiation

Although distributed machine learning has opened up many new and exciting research frontiers, fragmentation of models and data across different machines, nodes, and sites still results in considerable communication overhead, impeding reliable training in real-world contexts. The focus on gradients as the primary shared statistic during training has spawned a number of intuitive algorithms for distributed deep learning; however, gradient-centric training of large deep neural networks (DNNs) tends to be communication-heavy, often requiring additional adaptations such as sparsity constraints, compression, quantization, and more, to curtail bandwidth. We introduce an innovative, communication-friendly approach for training distributed DNNs, which capitalizes on the outer-product structure of the gradient as revealed by the mechanics of auto-differentiation. The exposed structure of the gradient evokes a new class of distributed learning algorithm, which is naturally more communication-efficient than full gradient sharing. Our approach, called distributed auto-differentiation (dAD), builds off a marriage of rank-based compression and the innate structure of the gradient as an outer-product. We demonstrate that dAD trains more efficiently than other state of the art distributed methods on modern architectures, such as transformers, when applied to large-scale text and imaging datasets. The future of distributed learning, we determine, need not be dominated by gradient-centric algorithms.

preprint2022arXiv

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.

preprint2022arXiv

Tasting the cake: evaluating self-supervised generalization on out-of-distribution multimodal MRI data

Self-supervised learning has enabled significant improvements on natural image benchmarks. However, there is less work in the medical imaging domain in this area. The optimal models have not yet been determined among the various options. Moreover, little work has evaluated the current applicability limits of novel self-supervised methods. In this paper, we evaluate a range of current contrastive self-supervised methods on out-of-distribution generalization in order to evaluate their applicability to medical imaging. We show that self-supervised models are not as robust as expected based on their results in natural imaging benchmarks and can be outperformed by supervised learning with dropout. We also show that this behavior can be countered with extensive augmentation. Our results highlight the need for out-of-distribution generalization standards and benchmarks to adopt the self-supervised methods in the medical imaging community.

preprint2020arXiv

A Bayesian incorporated linear non-Gaussian acyclic model for multiple directed graph estimation to study brain emotion circuit development in adolescence

Emotion perception is essential to affective and cognitive development which involves distributed brain circuits. The ability of emotion identification begins in infancy and continues to develop throughout childhood and adolescence. Understanding the development of brain's emotion circuitry may help us explain the emotional changes observed during adolescence. Our previous study delineated the trajectory of brain functional connectivity (FC) from late childhood to early adulthood during emotion identification tasks. In this work, we endeavour to deepen our understanding from association to causation. We proposed a Bayesian incorporated linear non-Gaussian acyclic model (BiLiNGAM), which incorporated our previous association model into the prior estimation pipeline. In particular, it can jointly estimate multiple directed acyclic graphs (DAGs) for multiple age groups at different developmental stages. Simulation results indicated more stable and accurate performance over various settings, especially when the sample size was small (high-dimensional cases). We then applied to the analysis of real data from the Philadelphia Neurodevelopmental Cohort (PNC). This included 855 individuals aged 8-22 years who were divided into five different adolescent stages. Our network analysis revealed the development of emotion-related intra- and inter- modular connectivity and pinpointed several emotion-related hubs. We further categorized the hubs into two types: in-hubs and out-hubs, as the center of receiving and distributing information. Several unique developmental hub structures and group-specific patterns were also discovered. Our findings help provide a causal understanding of emotion development in the human brain.

preprint2020arXiv

Causal inference of brain connectivity from fMRI with $ψ$-Learning Incorporated Linear non-Gaussian Acyclic Model ($ψ$-LiNGAM)

Functional connectivity (FC) has become a primary means of understanding brain functions by identifying brain network interactions and, ultimately, how those interactions produce cognitions. A popular definition of FC is by statistical associations between measured brain regions. However, this could be problematic since the associations can only provide spatial connections but not causal interactions among regions of interests. Hence, it is necessary to study their causal relationship. Directed acyclic graph (DAG) models have been applied in recent FC studies but often encountered problems such as limited sample sizes and large number of variables (namely high-dimensional problems), which lead to both computational difficulty and convergence issues. As a result, the use of DAG models is problematic, where the identification of DAG models in general is nondeterministic polynomial time hard (NP-hard). To this end, we propose a $ψ$-learning incorporated linear non-Gaussian acyclic model ($ψ$-LiNGAM). We use the association model ($ψ$-learning) to facilitate causal inferences and the model works well especially for high-dimensional cases. Our simulation results demonstrate that the proposed method is more robust and accurate than several existing ones in detecting graph structure and direction. We then applied it to the resting state fMRI (rsfMRI) data obtained from the publicly available Philadelphia Neurodevelopmental Cohort (PNC) to study the cognitive variance, which includes 855 individuals aged 8-22 years. Therein, we have identified three types of hub structure: the in-hub, out-hub and sum-hub, which correspond to the centers of receiving, sending and relaying information, respectively. We also detected 16 most important pairs of causal flows. Several of the results have been verified to be biologically significant.

preprint2020arXiv

Causality based Feature Fusion for Brain Neuro-Developmental Analysis

Human brain development is a complex and dynamic process that is affected by several factors such as genetics, sex hormones, and environmental changes. A number of recent studies on brain development have examined functional connectivity (FC) defined by the temporal correlation between time series of different brain regions. We propose to add the directional flow of information during brain maturation. To do so, we extract effective connectivity (EC) through Granger causality (GC) for two different groups of subjects, i.e., children and young adults. The motivation is that the inclusion of causal interaction may further discriminate brain connections between two age groups and help to discover new connections between brain regions. The contributions of this study are threefold. First, there has been a lack of attention to EC-based feature extraction in the context of brain development. To this end, we propose a new kernel-based GC (KGC) method to learn nonlinearity of complex brain network, where a reduced Sine hyperbolic polynomial (RSP) neural network was used as our proposed learner. Second, we used causality values as the weight for the directional connectivity between brain regions. Our findings indicated that the strength of connections was significantly higher in young adults relative to children. In addition, our new EC-based feature outperformed FC-based analysis from Philadelphia neurocohort (PNC) study with better discrimination of the different age groups. Moreover, the fusion of these two sets of features (FC + EC) improved brain age prediction accuracy by more than 4%, indicating that they should be used together for brain development studies.

preprint2020arXiv

Functional connectome fingerprinting: Identifying individuals and predicting cognitive function via deep learning

The dynamic characteristics of functional network connectivity have been widely acknowledged and studied. Both shared and unique information has been shown to be present in the connectomes. However, very little has been known about whether and how this common pattern can predict the individual variability of the brain, i.e. "brain fingerprinting", which attempts to reliably identify a particular individual from a pool of subjects. In this paper, we propose to enhance the individual uniqueness based on an autoencoder network. More specifically, we rely on the hypothesis that the common neural activities shared across individuals may lessen individual discrimination. By reducing contributions from shared activities, inter-subject variability can be enhanced. Results show that that refined connectomes utilizing an autoencoder with sparse dictionary learning can successfully distinguish one individual from the remaining participants with reasonably high accuracy (up to 99:5% for the rest-rest pair). Furthermore, high-level cognitive behavior (e.g., fluid intelligence, executive function, and language comprehension) can also be better predicted using refined functional connectivity profiles. As expected, the high-order association cortices contributed more to both individual discrimination and behavior prediction. The proposed approach provides a promising way to enhance and leverage the individualized characteristics of brain networks.

preprint2020arXiv

Interpretable multimodal fusion networks reveal mechanisms of brain cognition

Multimodal fusion benefits disease diagnosis by providing a more comprehensive perspective. Developing algorithms is challenging due to data heterogeneity and the complex within- and between-modality associations. Deep-network-based data-fusion models have been developed to capture the complex associations and the performance in diagnosis has been improved accordingly. Moving beyond diagnosis prediction, evaluation of disease mechanisms is critically important for biomedical research. Deep-network-based data-fusion models, however, are difficult to interpret, bringing about difficulties for studying biological mechanisms. In this work, we develop an interpretable multimodal fusion model, namely gCAM-CCL, which can perform automated diagnosis and result interpretation simultaneously. The gCAM-CCL model can generate interpretable activation maps, which quantify pixel-level contributions of the input features. This is achieved by combining intermediate feature maps using gradient-based weights. Moreover, the estimated activation maps are class-specific, and the captured cross-data associations are interest/label related, which further facilitates class-specific analysis and biological mechanism analysis. We validate the gCAM-CCL model on a brain imaging-genetic study, and show gCAM-CCL's performed well for both classification and mechanism analysis. Mechanism analysis suggests that during task-fMRI scans, several object recognition related regions of interests (ROIs) are first activated and then several downstream encoding ROIs get involved. Results also suggest that the higher cognition performing group may have stronger neurotransmission signaling while the lower cognition performing group may have problem in brain/neuron development, resulting from genetic variations.

preprint2020arXiv

Meta-modal Information Flow: A Method for Capturing Multimodal Modular Disconnectivity in Schizophrenia

Objective: Multimodal measurements of the same phenomena provide complementary information and highlight different perspectives, albeit each with their own limitations. A focus on a single modality may lead to incorrect inferences, which is especially important when a studied phenomenon is a disease. In this paper, we introduce a method that takes advantage of multimodal data in addressing the hypotheses of disconnectivity and dysfunction within schizophrenia (SZ). Methods: We start with estimating and visualizing links within and among extracted multimodal data features using a Gaussian graphical model (GGM). We then propose a modularity-based method that can be applied to the GGM to identify links that are associated with mental illness across a multimodal data set. Through simulation and real data, we show our approach reveals important information about disease-related network disruptions that are missed with a focus on a single modality. We use functional MRI (fMRI), diffusion MRI (dMRI), and structural MRI (sMRI) to compute the fractional amplitude of low frequency fluctuations (fALFF), fractional anisotropy (FA), and gray matter (GM) concentration maps. These three modalities are analyzed using our modularity method. Results: Our results show missing links that are only captured by the cross-modal information that may play an important role in disconnectivity between the components. Conclusion: We identified multimodal (fALFF, FA and GM) disconnectivity in the default mode network area in patients with SZ, which would not have been detectable in a single modality. Significance: The proposed approach provides an important new tool for capturing information that is distributed among multiple imaging modalities.