Vince Calhoun

Yuxiang Wei, Anees Abrol, Vince Calhoun

Recent advances in deep learning structured state space models, especially the Mamba architecture, have demonstrated remarkable performance improvements while maintaining linear complexity. In this study, we introduce functional spatiotemporal Mamba (FST-Mamba), a Mamba-based model designed for discovering neurological biomarkers using functional magnetic resonance imaging (fMRI). We focus on dynamic functional network connectivity (dFNC) derived from fMRI and propose a hierarchical spatiotemporal Mamba-based network that processes spatial and temporal information separately using Mamba-based encoders. Leveraging the topological uniqueness of the FNC matrix, we introduce a component-wise varied-scale aggregation (CVA) mechanism to aggregate connectivity across individual components within brain networks, enabling the model to capture component-level and network-level information. Additionally, we propose symmetric rotary position encoding (SymRope) to encode the relative positions of each functional connection while considering the symmetric nature of the FNC matrix. Experimental results demonstrate significant improvements in the proposed FST-Mamba model on various brain-based classification and regression tasks. We further show brain connectivities and dynamics that are crucial for the prediction. Our work reveals the substantial potential of attention-free sequence modeling in brain discovery. The codes are publicly available here: https://github.com/yuxiangwei0808/FunctionalMamba/tree/main.

Eloy Geenjaar, Amrit Kashyap, Noah Lewis et al. · gatech

Functional magnetic resonance imaging (fMRI) data contain complex spatiotemporal dynamics, thus researchers have developed approaches that reduce the dimensionality of the signal while extracting relevant and interpretable dynamics. Models of fMRI data that can perform whole-brain discovery of dynamical latent factors are understudied. The benefits of approaches such as linear independent component analysis models have been widely appreciated, however, nonlinear extensions of these models present challenges in terms of identification. Deep learning methods provide a way forward, but new methods for efficient spatial weight-sharing are critical to deal with the high dimensionality of the data and the presence of noise. Our approach generalizes weight sharing to non-Euclidean neuroimaging data by first performing spectral clustering based on the structural and functional similarity between voxels. The spectral clusters and their assignments can then be used as patches in an adapted multi-layer perceptron (MLP)-mixer model to share parameters among input points. To encourage temporally independent latent factors, we use an additional total correlation term in the loss. Our approach is evaluated on data with multiple motor sub-tasks to assess whether the model captures disentangled latent factors that correspond to each sub-task. Then, to assess the latent factors we find further, we compare the spatial location of each latent factor to the motor homunculus. Finally, we show that our approach captures task effects better than the current gold standard of source signal separation, independent component analysis (ICA).

Yuda Bi, Anees Abrol, Zening Fu et al.

Deep learning algorithms for predicting neuroimaging data have shown considerable promise in various applications. Prior work has demonstrated that deep learning models that take advantage of the data's 3D structure can outperform standard machine learning on several learning tasks. However, most prior research in this area has focused on neuroimaging data from adults. Within the Adolescent Brain and Cognitive Development (ABCD) dataset, a large longitudinal development study, we examine structural MRI data to predict gender and identify gender-related changes in brain structure. Results demonstrate that gender prediction accuracy is exceptionally high (>97%) with training epochs >200 and that this accuracy increases with age. Brain regions identified as the most discriminative in the task under study include predominantly frontal areas and the temporal lobe. When evaluating gender predictive changes specific to a two-year increase in age, a broader set of visual, cingulate, and insular regions are revealed. Our findings show a robust gender-related structural brain change pattern, even over a small age range. This suggests that it might be possible to study how the brain changes during adolescence by looking at how these changes are related to different behavioral and environmental factors.

Riyasat Ohib, Bishal Thapaliya, Pratyush Gaggenapalli et al.

Federated learning (FL) enables the training of a model leveraging decentralized data in client sites while preserving privacy by not collecting data. However, one of the significant challenges of FL is limited computation and low communication bandwidth in resource limited edge client nodes. To address this, several solutions have been proposed in recent times including transmitting sparse models and learning dynamic masks iteratively, among others. However, many of these methods rely on transmitting the model weights throughout the entire training process as they are based on ad-hoc or random pruning criteria. In this work, we propose Salient Grads, which simplifies the process of sparse training by choosing a data aware subnetwork before training, based on the model-parameter's saliency scores, which is calculated from the local client data. Moreover only highly sparse gradients are transmitted between the server and client models during the training process unlike most methods that rely on sharing the entire dense model in each round. We also demonstrate the efficacy of our method in a real world federated learning application and report improvement in wall-clock communication time.

Guang Yang, Arvind Rao, Christine Fernandez-Maloigne et al.

Artificial intelligence has become pervasive across disciplines and fields, and biomedical image and signal processing is no exception. The growing and widespread interest on the topic has triggered a vast research activity that is reflected in an exponential research effort. Through study of massive and diverse biomedical data, machine and deep learning models have revolutionized various tasks such as modeling, segmentation, registration, classification and synthesis, outperforming traditional techniques. However, the difficulty in translating the results into biologically/clinically interpretable information is preventing their full exploitation in the field. Explainable AI (XAI) attempts to fill this translational gap by providing means to make the models interpretable and providing explanations. Different solutions have been proposed so far and are gaining increasing interest from the community. This paper aims at providing an overview on XAI in biomedical data processing and points to an upcoming Special Issue on Deep Learning in Biomedical Image and Signal Processing of the IEEE Signal Processing Magazine that is going to appear in March 2022.

Sepehr Salem Ghahfarokhi, M. Moein Esfahani, Raj Sunderraman et al.

Deep learning has significantly advanced automated brain tumor diagnosis, yet clinical adoption remains limited by interpretability and computational constraints. Conventional models often act as opaque ''black boxes'' and fail to quantify the complex, irregular tumor boundaries that characterize malignant growth. To address these challenges, we present XMorph, an explainable and computationally efficient framework for fine-grained classification of three prominent brain tumor types: glioma, meningioma, and pituitary tumors. We propose an Information-Weighted Boundary Normalization (IWBN) mechanism that emphasizes diagnostically relevant boundary regions alongside nonlinear chaotic and clinically validated features, enabling a richer morphological representation of tumor growth. A dual-channel explainable AI module combines GradCAM++ visual cues with LLM-generated textual rationales, translating model reasoning into clinically interpretable insights. The proposed framework achieves a classification accuracy of 96.0%, demonstrating that explainability and high performance can co-exist in AI-based medical imaging systems. The source code and materials for XMorph are all publicly available at: https://github.com/ALSER-Lab/XMorph.

Eloy Geenjaar, Noah Lewis, Amrit Kashyap et al. · gatech

Communication within or between complex systems is commonplace in the natural sciences and fields such as graph neural networks. The brain is a perfect example of such a complex system, where communication between brain regions is constantly being orchestrated. To analyze communication, the brain is often split up into anatomical regions that each perform certain computations. These regions must interact and communicate with each other to perform tasks and support higher-level cognition. On a macroscale, these regions communicate through signal propagation along the cortex and along white matter tracts over longer distances. When and what types of signals are communicated over time is an unsolved problem and is often studied using either functional or structural data. In this paper, we propose a non-linear generative approach to communication from functional data. We address three issues with common connectivity approaches by explicitly modeling the directionality of communication, finding communication at each timestep, and encouraging sparsity. To evaluate our model, we simulate temporal data that has sparse communication between nodes embedded in it and show that our model can uncover the expected communication dynamics. Subsequently, we apply our model to temporal neural data from multiple tasks and show that our approach models communication that is more specific to each task. The specificity of our method means it can have an impact on the understanding of psychiatric disorders, which are believed to be related to highly specific communication between brain regions compared to controls. In sum, we propose a general model for dynamic communication learning on graphs, and show its applicability to a subfield of the natural sciences, with potential widespread scientific impact.

Yuda Bi, Anees Abrol, Zening Fu et al.

Vision Transformer (ViT) is a pioneering deep learning framework that can address real-world computer vision issues, such as image classification and object recognition. Importantly, ViTs are proven to outperform traditional deep learning models, such as convolutional neural networks (CNNs). Relatively recently, a number of ViT mutations have been transplanted into the field of medical imaging, thereby resolving a variety of critical classification and segmentation challenges, especially in terms of brain imaging data. In this work, we provide a novel multimodal deep learning pipeline, MultiCrossViT, which is capable of analyzing both structural MRI (sMRI) and static functional network connectivity (sFNC) data for the prediction of schizophrenia disease. On a dataset with minimal training subjects, our novel model can achieve an AUC of 0.832. Finally, we visualize multiple brain regions and covariance patterns most relevant to schizophrenia based on the resulting ViT attention maps by extracting features from transformer encoders.

Yuda Bi, Anees Abrol, Jing Sui et al.

The cross-modal synthesis between structural magnetic resonance imaging (sMRI) and functional network connectivity (FNC) is a relatively unexplored area in medical imaging, especially with respect to schizophrenia. This study employs conditional Vision Transformer Generative Adversarial Networks (cViT-GANs) to generate FNC data based on sMRI inputs. After training on a comprehensive dataset that included both individuals with schizophrenia and healthy control subjects, our cViT-GAN model effectively synthesized the FNC matrix for each subject, and then formed a group difference FNC matrix, obtaining a Pearson correlation of 0.73 with the actual FNC matrix. In addition, our FNC visualization results demonstrate significant correlations in particular subcortical brain regions, highlighting the model's capability of capturing detailed structural-functional associations. This performance distinguishes our model from conditional CNN-based GAN alternatives such as Pix2Pix. Our research is one of the first attempts to link sMRI and FNC synthesis, setting it apart from other cross-modal studies that concentrate on T1- and T2-weighted MR images or the fusion of MRI and CT scans.

Bishal Thapaliya, Esra Akbas, Jiayu Chen et al.

Resting-state functional magnetic resonance imaging (rsfMRI) is a powerful tool for investigating the relationship between brain function and cognitive processes as it allows for the functional organization of the brain to be captured without relying on a specific task or stimuli. In this paper, we present a novel modeling architecture called BrainRGIN for predicting intelligence (fluid, crystallized, and total intelligence) using graph neural networks on rsfMRI derived static functional network connectivity matrices. Extending from the existing graph convolution networks, our approach incorporates a clustering-based embedding and graph isomorphism network in the graph convolutional layer to reflect the nature of the brain sub-network organization and efficient network expression, in combination with TopK pooling and attention-based readout functions. We evaluated our proposed architecture on a large dataset, specifically the Adolescent Brain Cognitive Development Dataset, and demonstrated its effectiveness in predicting individual differences in intelligence. Our model achieved lower mean squared errors and higher correlation scores than existing relevant graph architectures and other traditional machine learning models for all of the intelligence prediction tasks. The middle frontal gyrus exhibited a significant contribution to both fluid and crystallized intelligence, suggesting their pivotal role in these cognitive processes. Total composite scores identified a diverse set of brain regions to be relevant which underscores the complex nature of total intelligence.

Xinhui Li, Alex Fedorov, Mrinal Mathur et al.

Deep learning has been widely applied in neuroimaging, including predicting brain-phenotype relationships from magnetic resonance imaging (MRI) volumes. MRI data usually requires extensive preprocessing prior to modeling, but variation introduced by different MRI preprocessing pipelines may lead to different scientific findings, even when using the identical data. Motivated by the data-centric perspective, we first evaluate how preprocessing pipeline selection can impact the downstream performance of a supervised learning model. We next propose two pipeline-invariant representation learning methodologies, MPSL and PXL, to improve robustness in classification performance and to capture similar neural network representations. Using 2000 human subjects from the UK Biobank dataset, we demonstrate that proposed models present unique and shared advantages, in particular that MPSL can be used to improve out-of-sample generalization to new pipelines, while PXL can be used to improve within-sample prediction performance. Both MPSL and PXL can learn more similar between-pipeline representations. These results suggest that our proposed models can be applied to mitigate pipeline-related biases, and to improve prediction robustness in brain-phenotype modeling.

Yanteng Zhang, Songheng Li, Zeyu Shen et al.

Large-scale brain imaging datasets provide unprecedented opportunities for developing domain foundation models through pretraining. However, unlike natural image datasets in computer vision, these neuroimaging data often exhibit high heterogeneity in quality, ranging from well-structured scans to severely distorted or incomplete brain volumes. This raises a fundamental question: can noise or low-quality scans contribute meaningfully to pretraining, or do they instead hinder model learning? In this study, we systematically explore the role of data quality level in pretraining and its impact on downstream tasks. Specifically, we perform pretraining on datasets with different quality levels and perform fine-tuning for brain age prediction on external cohorts. Our results show significant performance differences across quality levels, revealing both opportunities and limitations. We further discuss the gap between computer vision practices and clinical neuroimaging standards, emphasizing the necessity of domain-aware curation to ensure trusted and generalizable domain-specific foundation models.

M. Moein Esfahani, Sepehr Salem Ghahfarokhi, Mohammed Alser et al.

Recent advances in neuroimaging have deepened our understanding of the brain's complex functional and structural organization. Among these, functional Magnetic Resonance Imaging (fMRI) - particularly resting-state fMRI (rs-fMRI) - has emerged as a tool for identifying biomarkers of intrinsic brain connectivity and delineating large-scale neural networks. These networks are typically represented as volumetric spatial maps that capture functionally coherent brain regions and reflect individual differences in brain activity and structure. The spatial resolution of these maps plays an important role, as it determines the ability to localize functional units with precision, perform reliable brain parcellation, and detect subtle, spatially specific neurobiological alterations associated with development, aging, or disease. Therefore, improving the effective resolution of neuroimaging-derived maps holds significant promise for enabling more detailed insights into brain architecture and its relationship to behavior and pathology. To address this need, we propose NeuroGAN-3D, a novel 3D generative super-resolution model tailored to the computational demands of volumetric neuroimaging. Our model leverages a generative adversarial network architecture to enhance the spatial resolution of rs-fMRI spatial maps, significantly outperforming a conventional baseline.

Bishal Thapaliya, Robyn Miller, Jiayu Chen et al.

Resting-state functional magnetic resonance imaging (rs-fMRI) is a noninvasive technique pivotal for understanding human neural mechanisms of intricate cognitive processes. Most rs-fMRI studies compute a single static functional connectivity matrix across brain regions of interest, or dynamic functional connectivity matrices with a sliding window approach. These approaches are at risk of oversimplifying brain dynamics and lack proper consideration of the goal at hand. While deep learning has gained substantial popularity for modeling complex relational data, its application to uncovering the spatiotemporal dynamics of the brain is still limited. We propose a novel interpretable deep learning framework that learns goal-specific functional connectivity matrix directly from time series and employs a specialized graph neural network for the final classification. Our model, DSAM, leverages temporal causal convolutional networks to capture the temporal dynamics in both low- and high-level feature representations, a temporal attention unit to identify important time points, a self-attention unit to construct the goal-specific connectivity matrix, and a novel variant of graph neural network to capture the spatial dynamics for downstream classification. To validate our approach, we conducted experiments on the Human Connectome Project dataset with 1075 samples to build and interpret the model for the classification of sex group, and the Adolescent Brain Cognitive Development Dataset with 8520 samples for independent testing. Compared our proposed framework with other state-of-art models, results suggested this novel approach goes beyond the assumption of a fixed connectivity matrix and provides evidence of goal-specific brain connectivity patterns, which opens up the potential to gain deeper insights into how the human brain adapts its functional connectivity specific to the task at hand.

Eloy Geenjaar, Vince Calhoun

Mental and cognitive representations are believed to reside on low-dimensional, non-linear manifolds embedded within high-dimensional brain activity. Uncovering these manifolds is key to understanding individual differences in brain function, yet most existing machine learning methods either rely on population-level spatial alignment or assume data that is temporally structured, either because data is aligned among subjects or because event timings are known. We introduce a manifold learning framework that can capture subject-specific spatial variations across both structured and temporally unstructured neuroimaging data. On simulated data and two naturalistic fMRI datasets (Sherlock and Forrest Gump), our framework outperforms group-based baselines by recovering more accurate and individualized representations. We further show that the framework scales efficiently to large datasets and generalizes well to new subjects. To test this, we apply the framework to temporally unstructured resting-state fMRI data from individuals with schizophrenia and healthy controls. We further apply our method to a large resting-state fMRI dataset comprising individuals with schizophrenia and controls. In this setting, we demonstrate that the framework scales efficiently to large populations and generalizes robustly to unseen subjects. The learned subject-specific spatial maps our model finds reveal clinically relevant patterns, including increased activation in the basal ganglia, visual, auditory, and somatosensory regions, and decreased activation in the insula, inferior frontal gyrus, and angular gyrus. These findings suggest that our framework can uncover clinically relevant subject-specific brain activity patterns. Our approach thus provides a scalable and individualized framework for modeling brain activity, with applications in computational neuroscience and clinical research.

Keqi Han, Yao Su, Lifang He et al.

Functional brain connectome is crucial for deciphering the neural mechanisms underlying cognitive functions and neurological disorders. Graph deep learning models have recently gained tremendous popularity in this field. However, their actual effectiveness in modeling the brain connectome remains unclear. In this study, we re-examine graph deep learning models based on four large-scale neuroimaging studies encompassing diverse cognitive and clinical outcomes. Surprisingly, we find that the message aggregation mechanism, a hallmark of graph deep learning models, does not help with predictive performance as typically assumed, but rather consistently degrades it. To address this issue, we propose a hybrid model combining a linear model with a graph attention network through dual pathways, achieving robust predictions and enhanced interpretability by revealing both localized and global neural connectivity patterns. Our findings urge caution in adopting complex deep learning models for functional brain connectome analysis, emphasizing the need for rigorous experimental designs to establish tangible performance gains and perhaps more importantly, to pursue improvements in model interpretability.

Bishal Thapaliya, Esra Akbas, Ram Sapkota et al.

Resting-state functional magnetic resonance imaging (rs-fMRI) offers valuable insights into the human brain's functional organization and is a powerful tool for investigating the relationship between brain function and cognitive processes, as it allows for the functional organization of the brain to be captured without relying on a specific task or stimuli. In this study, we introduce a novel attention mechanism for graphs with subnetworks, named Self-Clustering Graph Transformer (SCGT), designed to handle the issue of uniform node updates in graph transformers. By using static functional connectivity (FC) correlation features as input to the transformer model, SCGT effectively captures the sub-network structure of the brain by performing cluster-specific updates to the nodes, unlike uniform node updates in vanilla graph transformers, further allowing us to learn and interpret the subclusters. We validate our approach on the Adolescent Brain Cognitive Development (ABCD) dataset, comprising 7,957 participants, for the prediction of total cognitive score and gender classification. Our results demonstrate that SCGT outperforms the vanilla graph transformer method and other recent models, offering a promising tool for modeling brain functional connectivity and interpreting the underlying subnetwork structures.

Riyasat Ohib, Bishal Thapaliya, Gintare Karolina Dziugaite et al.

In this work, we propose Salient Sparse Federated Learning (SSFL), a streamlined approach for sparse federated learning with efficient communication. SSFL identifies a sparse subnetwork prior to training, leveraging parameter saliency scores computed separately on local client data in non-IID scenarios, and then aggregated, to determine a global mask. Only the sparse model weights are communicated each round between the clients and the server. We validate SSFL's effectiveness using standard non-IID benchmarks, noting marked improvements in the sparsity--accuracy trade-offs. Finally, we deploy our method in a real-world federated learning framework and report improvement in communication time.

Sepehr Salem, M. Moein Esfahani, Jingyu Liu et al.

Data scarcity hinders deep learning for medical imaging. We propose a framework for breast cancer classification in thermograms that addresses this using a Diffusion Probabilistic Model (DPM) for data augmentation. Our DPM-based augmentation is shown to be superior to both traditional methods and a ProGAN baseline. The framework fuses deep features from a pre-trained ResNet-50 with handcrafted nonlinear features (e.g., Fractal Dimension) derived from U-Net segmented tumors. An XGBoost classifier trained on these fused features achieves 98.0\% accuracy and 98.1\% sensitivity. Ablation studies and statistical tests confirm that both the DPM augmentation and the nonlinear feature fusion are critical, statistically significant components of this success. This work validates the synergy between advanced generative models and interpretable features for creating highly accurate medical diagnostic tools.

Mohammadsajad Abavisani, Kseniya Solovyeva, David Danks et al.

Learning graphical causal structures from time series data presents significant challenges, especially when the measurement frequency does not match the causal timescale of the system. This often leads to a set of equally possible underlying causal graphs due to information loss from sub-sampling (i.e., not observing all possible states of the system throughout time). Our research addresses this challenge by incorporating the effects of sub-sampling in the derivation of causal graphs, resulting in more accurate and intuitive outcomes. We use a constraint optimization approach, specifically answer set programming (ASP), to find the optimal set of answers. ASP not only identifies the most probable underlying graph, but also provides an equivalence class of possible graphs for expert selection. In addition, using ASP allows us to leverage graph theory to further prune the set of possible solutions, yielding a smaller, more accurate answer set significantly faster than traditional approaches. We validate our approach on both simulated data and empirical structural brain connectivity, and demonstrate its superiority over established methods in these experiments. We further show how our method can be used as a meta-approach on top of established methods to obtain, on average, 12% improvement in F1 score. In addition, we achieved state of the art results in terms of precision and recall of reconstructing causal graph from sub-sampled time series data. Finally, our method shows robustness to varying degrees of sub-sampling on realistic simulations, whereas other methods perform worse for higher rates of sub-sampling.

Oktay Agcaoglu, Rogers F. Silva, Deniz Alacam et al. · gatech

Different brain imaging modalities offer unique insights into brain function and structure. Combining them enhances our understanding of neural mechanisms. Prior multimodal studies fusing functional MRI (fMRI) and structural MRI (sMRI) have shown the benefits of this approach. Since sMRI lacks temporal data, existing fusion methods often compress fMRI temporal information into summary measures, sacrificing rich temporal dynamics. Motivated by the observation that covarying networks are identified in both sMRI and resting-state fMRI, we developed a novel fusion method, by combining deep learning frameworks, copulas and independent component analysis (ICA), named copula linked parallel ICA (CLiP-ICA). This method estimates independent sources for each modality and links the spatial sources of fMRI and sMRI using a copula-based model for more flexible integration of temporal and spatial data. We tested CLiP-ICA using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our results showed that CLiP-ICA effectively captures both strongly and weakly linked sMRI and fMRI networks, including the cerebellum, sensorimotor, visual, cognitive control, and default mode networks. It revealed more meaningful components and fewer artifacts, addressing the long-standing issue of optimal model order in ICA. CLiP-ICA also detected complex functional connectivity patterns across stages of cognitive decline, with cognitively normal subjects generally showing higher connectivity in sensorimotor and visual networks compared to patients with Alzheimer, along with patterns suggesting potential compensatory mechanisms.

Nagur Shareef Shaik, Teja Krishna Cherukuri, Vince Calhoun et al.

Schizophrenia is a debilitating, chronic mental disorder that significantly impacts an individual's cognitive abilities, behavior, and social interactions. It is characterized by subtle morphological changes in the brain, particularly in the gray matter. These changes are often imperceptible through manual observation, demanding an automated approach to diagnosis. This study introduces a deep learning methodology for the classification of individuals with Schizophrenia. We achieve this by implementing a diversified attention mechanism known as Spatial Sequence Attention (SSA) which is designed to extract and emphasize significant feature representations from structural MRI (sMRI). Initially, we employ the transfer learning paradigm by leveraging pre-trained DenseNet to extract initial feature maps from the final convolutional block which contains morphological alterations associated with Schizophrenia. These features are further processed by the proposed SSA to capture and emphasize intricate spatial interactions and relationships across volumes within the brain. Our experimental studies conducted on a clinical dataset have revealed that the proposed attention mechanism outperforms the existing Squeeze & Excitation Network for Schizophrenia classification.

Eloy Geenjaar, Donghyun Kim, Riyasat Ohib et al.

The neural dynamics underlying brain activity are critical to understanding cognitive processes and mental disorders. However, current voxel-based whole-brain dimensionality reduction techniques fall short of capturing these dynamics, producing latent timeseries that inadequately relate to behavioral tasks. To address this issue, we introduce a novel approach to learning low-dimensional approximations of neural dynamics by using a sequential variational autoencoder (SVAE) that represents the latent dynamical system via a neural ordinary differential equation (NODE). Importantly, our method finds smooth dynamics that can predict cognitive processes with accuracy higher than classical methods. Our method also shows improved spatial localization to task-relevant brain regions and identifies well-known structures such as the motor homunculus from fMRI motor task recordings. We also find that non-linear projections to the latent space enhance performance for specific tasks, offering a promising direction for future research. We evaluate our approach on various task-fMRI datasets, including motor, working memory, and relational processing tasks, and demonstrate that it outperforms widely used dimensionality reduction techniques in how well the latent timeseries relates to behavioral sub-tasks, such as left-hand or right-hand tapping. Additionally, we replace the NODE with a recurrent neural network (RNN) and compare the two approaches to understand the importance of explicitly learning a dynamical system. Lastly, we analyze the robustness of the learned dynamical systems themselves and find that their fixed points are robust across seeds, highlighting our method's potential for the analysis of cognitive processes as dynamical systems.

Usman Mahmood, Zening Fu, Vince Calhoun et al.

Recently, methods that represent data as a graph, such as graph neural networks (GNNs) have been successfully used to learn data representations and structures to solve classification and link prediction problems. The applications of such methods are vast and diverse, but most of the current work relies on the assumption of a static graph. This assumption does not hold for many highly dynamic systems, where the underlying connectivity structure is non-stationary and is mostly unobserved. Using a static model in these situations may result in sub-optimal performance. In contrast, modeling changes in graph structure with time can provide information about the system whose applications go beyond classification. Most work of this type does not learn effective connectivity and focuses on cross-correlation between nodes to generate undirected graphs. An undirected graph is unable to capture direction of an interaction which is vital in many fields, including neuroscience. To bridge this gap, we developed dynamic effective connectivity estimation via neural network training (DECENNT), a novel model to learn an interpretable directed and dynamic graph induced by the downstream classification/prediction task. DECENNT outperforms state-of-the-art (SOTA) methods on five different tasks and infers interpretable task-specific dynamic graphs. The dynamic graphs inferred from functional neuroimaging data align well with the existing literature and provide additional information. Additionally, the temporal attention module of DECENNT identifies time-intervals crucial for predictive downstream task from multivariate time series data.

Usman Mahmood, Zening Fu, Vince Calhoun et al.

Functional connectivity (FC) studies have demonstrated the overarching value of studying the brain and its disorders through the undirected weighted graph of fMRI correlation matrix. Most of the work with the FC, however, depends on the way the connectivity is computed, and further depends on the manual post-hoc analysis of the FC matrices. In this work we propose a deep learning architecture BrainGNN that learns the connectivity structure as part of learning to classify subjects. It simultaneously applies a graphical neural network to this learned graph and learns to select a sparse subset of brain regions important to the prediction task. We demonstrate the model's state-of-the-art classification performance on a schizophrenia fMRI dataset and demonstrate how introspection leads to disorder relevant findings. The graphs learned by the model exhibit strong class discrimination and the sparse subset of relevant regions are consistent with the schizophrenia literature.

Usman Mahmood, Zening Fu, Vince Calhoun et al.

Discovering distinct features and their relations from data can help us uncover valuable knowledge crucial for various tasks, e.g., classification. In neuroimaging, these features could help to understand, classify, and possibly prevent brain disorders. Model introspection of highly performant overparameterized deep learning (DL) models could help find these features and relations. However, to achieve high-performance level DL models require numerous labeled training samples ($n$) rarely available in many fields. This paper presents a pre-training method involving graph convolutional/neural networks (GCNs/GNNs), based on maximizing mutual information between two high-level embeddings of an input sample. Many of the recently proposed pre-training methods pre-train one of many possible networks of an architecture. Since almost every DL model is an ensemble of multiple networks, we take our high-level embeddings from two different networks of a model --a convolutional and a graph network--. The learned high-level graph latent representations help increase performance for downstream graph classification tasks and bypass the need for a high number of labeled data samples. We apply our method to a neuroimaging dataset for classifying subjects into healthy control (HC) and schizophrenia (SZ) groups. Our experiments show that the pre-trained model significantly outperforms the non-pre-trained model and requires $50\%$ less data for similar performance.

Usman Mahmood, Zening Fu, Vince Calhoun et al.

Multivariate dynamical processes can often be intuitively described by a weighted connectivity graph between components representing each individual time-series. Even a simple representation of this graph as a Pearson correlation matrix may be informative and predictive as demonstrated in the brain imaging literature. However, there is a consensus expectation that powerful graph neural networks (GNNs) should perform better in similar settings. In this work, we present a model that is considerably shallow than deep GNNs, yet outperforms them in predictive accuracy in a brain imaging application. Our model learns the autoregressive structure of individual time series and estimates directed connectivity graphs between the learned representations via a self-attention mechanism in an end-to-end fashion. The supervised training of the model as a classifier between patients and controls results in a model that generates directed connectivity graphs and highlights the components of the time-series that are predictive for each subject. We demonstrate our results on a functional neuroimaging dataset classifying schizophrenia patients and controls.

Eloy Geenjaar, Tonya White, Vince Calhoun

We propose to apply non-linear representation learning to voxelwise rs-fMRI data. Learning the non-linear representations is done using a variational autoencoder (VAE). The VAE is trained on voxelwise rs-fMRI data and performs non-linear dimensionality reduction that retains meaningful information. The retention of information in the model's representations is evaluated using downstream age regression and sex classification tasks. The results on these tasks are highly encouraging and a linear regressor trained with the representations of our unsupervised model performs almost as well as a supervised neural network, trained specifically for age regression on the same dataset. The model is also evaluated with a schizophrenia diagnosis prediction task, to assess its feasibility as a dimensionality reduction method for neuropsychiatric datasets. These results highlight the potential for pre-training on a larger set of individuals who do not have mental illness, to improve the downstream neuropsychiatric task results. The pre-trained model is fine-tuned for a variable number of epochs on a schizophrenia dataset and we find that fine-tuning for 1 epoch yields the best results. This work therefore not only opens up non-linear dimensionality reduction for voxelwise rs-fMRI data but also shows that pre-training a deep learning model on voxelwise rs-fMRI datasets greatly increases performance even on smaller datasets. It also opens up the ability to look at the distribution of rs-fMRI time series in the latent space of the VAE for heterogeneous neuropsychiatric disorders like schizophrenia in future work. This can be complemented with the generative aspect of the model that allows us to reconstruct points from the model's latent space back into brain space and obtain an improved understanding of the relation that the VAE learns between subjects, timepoints, and a subject's characteristics.

Eloy Geenjaar, Noah Lewis, Zening Fu et al.

Neuroimaging studies often involve the collection of multiple data modalities. These modalities contain both shared and mutually exclusive information about the brain. This work aims at finding a scalable and interpretable method to fuse the information of multiple neuroimaging modalities using a variational autoencoder (VAE). To provide an initial assessment, this work evaluates the representations that are learned using a schizophrenia classification task. A support vector machine trained on the representations achieves an area under the curve for the classifier's receiver operating characteristic (ROC-AUC) of 0.8610.

Hafiz Imtiaz, Jafar Mohammadi, Rogers Silva et al.

Blind source separation algorithms such as independent component analysis (ICA) are widely used in the analysis of neuroimaging data. In order to leverage larger sample sizes, different data holders/sites may wish to collaboratively learn feature representations. However, such datasets are often privacy-sensitive, precluding centralized analyses that pool the data at a single site. In this work, we propose a differentially private algorithm for performing ICA in a decentralized data setting. Conventional approaches to decentralized differentially private algorithms may introduce too much noise due to the typically small sample sizes at each site. We propose a novel protocol that uses correlated noise to remedy this problem. We show that our algorithm outperforms existing approaches on synthetic and real neuroimaging datasets and demonstrate that it can sometimes reach the same level of utility as the corresponding non-private algorithm. This indicates that it is possible to have meaningful utility while preserving privacy.

Marie Roald, Suchita Bhinge, Chunying Jia et al.

Characterizing time-evolving networks is a challenging task, but it is crucial for understanding the dynamic behavior of complex systems such as the brain. For instance, how spatial networks of functional connectivity in the brain evolve during a task is not well-understood. A traditional approach in neuroimaging data analysis is to make simplifications through the assumption of static spatial networks. In this paper, without assuming static networks in time and/or space, we arrange the temporal data as a higher-order tensor and use a tensor factorization model called PARAFAC2 to capture underlying patterns (spatial networks) in time-evolving data and their evolution. Numerical experiments on simulated data demonstrate that PARAFAC2 can successfully reveal the underlying networks and their dynamics. We also show the promising performance of the model in terms of tracing the evolution of task-related functional connectivity in the brain through the analysis of functional magnetic resonance imaging data.

Alvaro Ulloa, Sergey Plis, Vince Calhoun

The wide variety of brain imaging technologies allows us to exploit information inherent to different data modalities. The richness of multimodal datasets may increase predictive power and reveal latent variables that otherwise would have not been found. However, the analysis of multimodal data is often conducted by assuming linear interactions which impact the accuracy of the results. We propose the use of a multimodal multi-layer perceptron model to enhance the predictive power of structural and functional magnetic resonance imaging (sMRI and fMRI) combined. We also use a synthetic data generator to pre-train each modality input layers, alleviating the effects of the small sample size that is often the case for brain imaging modalities. The proposed model improved the average and uncertainty of the area under the ROC curve to 0.850+-0.051 compared to the best results on individual modalities (0.741+-0.075 for sMRI, and 0.833+-0.050 for fMRI).

Alex Fedorov, Eswar Damaraju, Vince Calhoun et al.

Large scale studies of group differences in healthy controls and patients and screenings for early stage disease prevention programs require processing and analysis of extensive multisubject datasets. Complexity of the task increases even further when segmenting structural MRI of the brain into an atlas with more than 50 regions. Current automatic approaches are time-consuming and hardly scalable; they often involve many error prone intermediate steps and don't utilize other available modalities. To alleviate these problems, we propose a feedforward fully convolutional neural network trained on the output produced by the state of the art models. Incredible speed due to available powerful GPUs neural network makes this analysis much easier and faster (from $>10$ hours to a minute). The proposed model is more than two orders of magnitudes faster than the state of the art and yet as accurate. We have evaluated the network's performance by comparing it with the state of the art in the task of differentiating region volumes of healthy controls and patients with schizophrenia on a dataset with 311 subjects. This comparison provides a strong evidence that speed did not harm the accuracy. The overall quality may also be increased by utilizing multi-modal datasets (not an easy task for other models) by simple adding more modalities as an input. Our model will be useful in large-scale studies as well as in clinical care solutions, where it can significantly reduce delay between the patient screening and the result.

Md. Ashad Alam, Hui-Yi Lin, Vince Calhoun et al.

In this study, we tested the interaction effect of multimodal datasets using a novel method called the kernel method for detecting higher order interactions among biologically relevant mulit-view data. Using a semiparametric method on a reproducing kernel Hilbert space (RKHS), we used a standard mixed-effects linear model and derived a score-based variance component statistic that tests for higher order interactions between multi-view data. The proposed method offers an intangible framework for the identification of higher order interaction effects (e.g., three way interaction) between genetics, brain imaging, and epigenetic data. Extensive numerical simulation studies were first conducted to evaluate the performance of this method. Finally, this method was evaluated using data from the Mind Clinical Imaging Consortium (MCIC) including single nucleotide polymorphism (SNP) data, functional magnetic resonance imaging (fMRI) scans, and deoxyribonucleic acid (DNA) methylation data, respectfully, in schizophrenia patients and healthy controls. We treated each gene-derived SNPs, region of interest (ROI) and gene-derived DNA methylation as a single testing unit, which are combined into triplets for evaluation. In addition, cardiovascular disease risk factors such as age, gender, and body mass index were assessed as covariates on hippocampal volume and compared between triplets. Our method identified $13$-triplets ($p$-values $\leq 0.001$) that included $6$ gene-derived SNPs, $10$ ROIs, and $6$ gene-derived DNA methylations that correlated with changes in hippocampal volume, suggesting that these triplets may be important in explaining schizophrenia-related neurodegeneration. With strong evidence ($p$-values $\leq 0.000001$), the triplet ({\bf MAGI2, CRBLCrus1.L, FBXO28}) has the potential to distinguish schizophrenia patients from the healthy control variations.

Alexej Gossmann, Pascal Zille, Vince Calhoun et al.

Reducing the number of false discoveries is presently one of the most pressing issues in the life sciences. It is of especially great importance for many applications in neuroimaging and genomics, where datasets are typically high-dimensional, which means that the number of explanatory variables exceeds the sample size. The false discovery rate (FDR) is a criterion that can be employed to address that issue. Thus it has gained great popularity as a tool for testing multiple hypotheses. Canonical correlation analysis (CCA) is a statistical technique that is used to make sense of the cross-correlation of two sets of measurements collected on the same set of samples (e.g., brain imaging and genomic data for the same mental illness patients), and sparse CCA extends the classical method to high-dimensional settings. Here we propose a way of applying the FDR concept to sparse CCA, and a method to control the FDR. The proposed FDR correction directly influences the sparsity of the solution, adapting it to the unknown true sparsity level. Theoretical derivation as well as simulation studies show that our procedure indeed keeps the FDR of the canonical vectors below a user-specified target level. We apply the proposed method to an imaging genomics dataset from the Philadelphia Neurodevelopmental Cohort. Our results link the brain connectivity profiles derived from brain activity during an emotion identification task, as measured by functional magnetic resonance imaging (fMRI), to the corresponding subjects' genomic data.

Alex Fedorov, Jeremy Johnson, Eswar Damaraju et al.

Segmenting a structural magnetic resonance imaging (MRI) scan is an important pre-processing step for analytic procedures and subsequent inferences about longitudinal tissue changes. Manual segmentation defines the current gold standard in quality but is prohibitively expensive. Automatic approaches are computationally intensive, incredibly slow at scale, and error prone due to usually involving many potentially faulty intermediate steps. In order to streamline the segmentation, we introduce a deep learning model that is based on volumetric dilated convolutions, subsequently reducing both processing time and errors. Compared to its competitors, the model has a reduced set of parameters and thus is easier to train and much faster to execute. The contrast in performance between the dilated network and its competitors becomes obvious when both are tested on a large dataset of unprocessed human brain volumes. The dilated network consistently outperforms not only another state-of-the-art deep learning approach, the up convolutional network, but also the ground truth on which it was trained. Not only can the incredible speed of our model make large scale analyses much easier but we also believe it has great potential in a clinical setting where, with little to no substantial delay, a patient and provider can go over test results.

R Devon Hjelm, Eswar Damaraju, Kyunghyun Cho et al.

We introduce a novel recurrent neural network (RNN) approach to account for temporal dynamics and dependencies in brain networks observed via functional magnetic resonance imaging (fMRI). Our approach directly parameterizes temporal dynamics through recurrent connections, which can be used to formulate blind source separation with a conditional (rather than marginal) independence assumption, which we call RNN-ICA. This formulation enables us to visualize the temporal dynamics of both first order (activity) and second order (directed connectivity) information in brain networks that are widely studied in a static sense, but not well-characterized dynamically. RNN-ICA predicts dynamics directly from the recurrent states of the RNN in both task and resting state fMRI. Our results show both task-related and group-differentiating directed connectivity.

Owen Richfield, Md. Ashad Alam, Vince Calhoun et al.

Kernel and Multiple Kernel Canonical Correlation Analysis (CCA) are employed to classify schizophrenic and healthy patients based on their SNPs, DNA Methylation and fMRI data. Kernel and Multiple Kernel CCA are popular methods for finding nonlinear correlations between high-dimensional datasets. Data was gathered from 183 patients, 79 with schizophrenia and 104 healthy controls. Kernel and Multiple Kernel CCA represent new avenues for studying schizophrenia, because, to our knowledge, these methods have not been used on these data before. Classification is performed via k-means clustering on the kernel matrix outputs of the Kernel and Multiple Kernel CCA algorithm. Accuracies of the Kernel and Multiple Kernel CCA classification are compared to that of the regularized linear CCA algorithm classification, and are found to be significantly more accurate. Both algorithms demonstrate maximal accuracies when the combination of DNA methylation and fMRI data are used, and experience lower accuracies when the SNP data are incorporated.

R Devon Hjelm, Kyunghyun Cho, Junyoung Chung et al.

Variational methods that rely on a recognition network to approximate the posterior of directed graphical models offer better inference and learning than previous methods. Recent advances that exploit the capacity and flexibility in this approach have expanded what kinds of models can be trained. However, as a proposal for the posterior, the capacity of the recognition network is limited, which can constrain the representational power of the generative model and increase the variance of Monte Carlo estimates. To address these issues, we introduce an iterative refinement procedure for improving the approximate posterior of the recognition network and show that training with the refined posterior is competitive with state-of-the-art methods. The advantages of refinement are further evident in an increased effective sample size, which implies a lower variance of gradient estimates.