Pamela Ventola

Jiyao Wang, Peiyu Duan, Nicha C. Dvornek et al.

Functional magnetic resonance imaging (fMRI) is a powerful tool for investigating human brain function. However, the high cost of data acquisition and the inherent subjectivity of psychiatric rating scales often lead to datasets with small sample sizes and variable label quality, especially when targeting a specific neurological condition. Combined with the inherently high dimensionality of fMRI data, these limitations substantially increase the risk of model overfitting. Recent years have seen growing interest in developing fMRI foundation models by combining multiple datasets; however, the computational resources needed for pretraining and fine-tuning are often prohibitive. We show that a lightweight self-supervised framework yields representations that generalize across diverse downstream tasks, outperforming fully supervised baselines and approaching the performance of large-scale models. We introduce BrainSimSiam, a data-efficient self-supervised representation learning framework that leverages positive-only data pairs to learn robust and generalizable features. We demonstrate that the learned representations achieve strong performance across multiple downstream classification and regression tasks, highlighting the potential of BrainSimSiam for data-limited neuroimaging applications.

Beibin Li, Nicholas Nuechterlein, Erin Barney et al.

Identifying oculomotor behaviors relevant for eye-tracking applications is a critical but often challenging task. Aiming to automatically learn and extract knowledge from existing eye-tracking data, we develop a novel method that creates rich representations of oculomotor scanpaths to facilitate the learning of downstream tasks. The proposed stimulus-agnostic Oculomotor Behavior Framework (OBF) model learns human oculomotor behaviors from unsupervised and semi-supervised tasks, including reconstruction, predictive coding, fixation identification, and contrastive learning tasks. The resultant pre-trained OBF model can be used in a variety of applications. Our pre-trained model outperforms baseline approaches and traditional scanpath methods in autism spectrum disorder and viewed-stimulus classification tasks. Ablation experiments further show our proposed method could achieve even better results with larger model sizes and more diverse eye-tracking training datasets, supporting the model's potential for future eye-tracking applications. Open source code: http://github.com/BeibinLi/OBF.

Jiyao Wang, Nicha C. Dvornek, Peiyu Duan et al.

In recent years, graph neural networks (GNNs) have been widely applied in the analysis of brain fMRI, yet defining the connectivity between ROIs remains a challenge in noisy fMRI data. Among all approaches, Functional Connectome (FC) is the most popular method. Computed by the correlation coefficients between ROI time series, FC is a powerful and computationally efficient way to estimate ROI connectivity. However, it is well known for neglecting structural connections and causality in ROI interactions. Also, FC becomes much more noisy in the short spatio-temporal sliding-window subsequences of fMRI. Effective Connectome (EC) is proposed as a directional alternative, but is difficult to accurately estimate. Furthermore, for optimal GNN performance, usually only a small percentage of the strongest connections are selected as sparse edges, resulting in oversimplification of complex brain connections. To tackle these challenges, we propose the Spatio-Temporal Node Attention Graph Neural Network (STNAGNN) as a data-driven alternative that combines sparse predefined FC with dense data-driven spatio-temporal connections, allowing for flexible and spatio-temporal learning of ROI interaction patterns.

Nicha C. Dvornek, Pamela Ventola, James S. Duncan

We propose a method for estimating more reproducible functional networks that are more strongly associated with dynamic task activity by using recurrent neural networks with long short term memory (LSTMs). The LSTM model is trained in an unsupervised manner to learn to generate the functional magnetic resonance imaging (fMRI) time-series data in regions of interest. The learned functional networks can then be used for further analysis, e.g., correlation analysis to determine functional networks that are strongly associated with an fMRI task paradigm. We test our approach and compare to other methods for decomposing functional networks from fMRI activity on 2 related but separate datasets that employ a biological motion perception task. We demonstrate that the functional networks learned by the LSTM model are more strongly associated with the task activity and dynamics compared to other approaches. Furthermore, the patterns of network association are more closely replicated across subjects within the same dataset as well as across datasets. More reproducible functional networks are essential for better characterizing the neural correlates of a target task.

Nicha C. Dvornek, Xiaoxiao Li, Juntang Zhuang et al.

Heterogeneous presentation of a neurological disorder suggests potential differences in the underlying pathophysiological changes that occur in the brain. We propose to model heterogeneous patterns of functional network differences using a demographic-guided attention (DGA) mechanism for recurrent neural network models for prediction from functional magnetic resonance imaging (fMRI) time-series data. The context computed from the DGA head is used to help focus on the appropriate functional networks based on individual demographic information. We demonstrate improved classification on 3 subsets of the ABIDE I dataset used in published studies that have previously produced state-of-the-art results, evaluating performance under a leave-one-site-out cross-validation framework for better generalizeability to new data. Finally, we provide examples of interpreting functional network differences based on individual demographic variables.

Juntang Zhuang, Nicha Dvornek, Sekhar Tatikonda et al.

Dynamic causal modeling (DCM) is a Bayesian framework to infer directed connections between compartments, and has been used to describe the interactions between underlying neural populations based on functional neuroimaging data. DCM is typically analyzed with the expectation-maximization (EM) algorithm. However, because the inversion of a large-scale continuous system is difficult when noisy observations are present, DCM by EM is typically limited to a small number of compartments ($<10$). Another drawback with the current method is its complexity; when the forward model changes, the posterior mean changes, and we need to re-derive the algorithm for optimization. In this project, we propose the Multiple-Shooting Adjoint (MSA) method to address these limitations. MSA uses the multiple-shooting method for parameter estimation in ordinary differential equations (ODEs) under noisy observations, and is suitable for large-scale systems such as whole-brain analysis in functional MRI (fMRI). Furthermore, MSA uses the adjoint method for accurate gradient estimation in the ODE; since the adjoint method is generic, MSA is a generic method for both linear and non-linear systems, and does not require re-derivation of the algorithm as in EM. We validate MSA in extensive experiments: 1) in toy examples with both linear and non-linear models, we show that MSA achieves better accuracy in parameter value estimation than EM; furthermore, MSA can be successfully applied to large systems with up to 100 compartments; and 2) using real fMRI data, we apply MSA to the estimation of the whole-brain effective connectome and show improved classification of autism spectrum disorder (ASD) vs. control compared to using the functional connectome. The package is provided \url{https://jzkay12.github.io/TorchDiffEqPack}

Xiaoxiao Li, Yuan Zhou, Nicha C. Dvornek et al.

Understanding how certain brain regions relate to a specific neurological disorder has been an important area of neuroimaging research. A promising approach to identify the salient regions is using Graph Neural Networks (GNNs), which can be used to analyze graph structured data, e.g. brain networks constructed by functional magnetic resonance imaging (fMRI). We propose an interpretable GNN framework with a novel salient region selection mechanism to determine neurological brain biomarkers associated with disorders. Specifically, we design novel regularized pooling layers that highlight salient regions of interests (ROIs) so that we can infer which ROIs are important to identify a certain disease based on the node pooling scores calculated by the pooling layers. Our proposed framework, Pooling Regularized-GNN (PR-GNN), encourages reasonable ROI-selection and provides flexibility to preserve either individual- or group-level patterns. We apply the PR-GNN framework on a Biopoint Autism Spectral Disorder (ASD) fMRI dataset. We investigate different choices of the hyperparameters and show that PR-GNN outperforms baseline methods in terms of classification accuracy. The salient ROI detection results show high correspondence with the previous neuroimaging-derived biomarkers for ASD.

Xiaoxiao Li, Yufeng Gu, Nicha Dvornek et al.

Deep learning models have shown their advantage in many different tasks, including neuroimage analysis. However, to effectively train a high-quality deep learning model, the aggregation of a significant amount of patient information is required. The time and cost for acquisition and annotation in assembling, for example, large fMRI datasets make it difficult to acquire large numbers at a single site. However, due to the need to protect the privacy of patient data, it is hard to assemble a central database from multiple institutions. Federated learning allows for population-level models to be trained without centralizing entities' data by transmitting the global model to local entities, training the model locally, and then averaging the gradients or weights in the global model. However, some studies suggest that private information can be recovered from the model gradients or weights. In this work, we address the problem of multi-site fMRI classification with a privacy-preserving strategy. To solve the problem, we propose a federated learning approach, where a decentralized iterative optimization algorithm is implemented and shared local model weights are altered by a randomization mechanism. Considering the systemic differences of fMRI distributions from different sites, we further propose two domain adaptation methods in this federated learning formulation. We investigate various practical aspects of federated model optimization and compare federated learning with alternative training strategies. Overall, our results demonstrate that it is promising to utilize multi-site data without data sharing to boost neuroimage analysis performance and find reliable disease-related biomarkers. Our proposed pipeline can be generalized to other privacy-sensitive medical data analysis problems.

Beibin Li, Nicholas Nuechterlein, Erin Barney et al.

In genomic analysis, biomarker discovery, image recognition, and other systems involving machine learning, input variables can often be organized into different groups by their source or semantic category. Eliminating some groups of variables can expedite the process of data acquisition and avoid over-fitting. Researchers have used the group lasso to ensure group sparsity in linear models and have extended it to create compact neural networks in meta-learning. Different from previous studies, we use multi-layer non-linear neural networks to find sparse groups for input variables. We propose a new loss function to regularize parameters for grouped input variables, design a new optimization algorithm for this loss function, and test these methods in three real-world settings. We achieve group sparsity for three datasets, maintaining satisfying results while excluding one nucleotide position from an RNA splicing experiment, excluding 89.9% of stimuli from an eye-tracking experiment, and excluding 60% of image rows from an experiment on the MNIST dataset.

Xiaoxiao Li, Nicha C. Dvornek, Juntang Zhuang et al.

Significant progress has been made using fMRI to characterize the brain changes that occur in ASD, a complex neuro-developmental disorder. However, due to the high dimensionality and low signal-to-noise ratio of fMRI, embedding informative and robust brain regional fMRI representations for both graph-level classification and region-level functional difference detection tasks between ASD and healthy control (HC) groups is difficult. Here, we model the whole brain fMRI as a graph, which preserves geometrical and temporal information and use a Graph Neural Network (GNN) to learn from the graph-structured fMRI data. We investigate the potential of including mutual information (MI) loss (Infomax), which is an unsupervised term encouraging large MI of each nodal representation and its corresponding graph-level summarized representation to learn a better graph embedding. Specifically, this work developed a pipeline including a GNN encoder, a classifier and a discriminator, which forces the encoded nodal representations to both benefit classification and reveal the common nodal patterns in a graph. We simultaneously optimize graph-level classification loss and Infomax. We demonstrated that Infomax graph embedding improves classification performance as a regularization term. Furthermore, we found separable nodal representations of ASD and HC groups in prefrontal cortex, cingulate cortex, visual regions, and other social, emotional and execution related brain regions. In contrast with GNN with classification loss only, the proposed pipeline can facilitate training more robust ASD classification models. Moreover, the separable nodal representations can detect the functional differences between the two groups and contribute to revealing new ASD biomarkers.

Juntang Zhuang, Nicha C. Dvornek, Xiaoxiao Li et al.

Determining biomarkers for autism spectrum disorder (ASD) is crucial to understanding its mechanisms. Recently deep learning methods have achieved success in the classification task of ASD using fMRI data. However, due to the black-box nature of most deep learning models, it's hard to perform biomarker selection and interpret model decisions. The recently proposed invertible networks can accurately reconstruct the input from its output, and have the potential to unravel the black-box representation. Therefore, we propose a novel method to classify ASD and identify biomarkers for ASD using the connectivity matrix calculated from fMRI as the input. Specifically, with invertible networks, we explicitly determine the decision boundary and the projection of data points onto the boundary. Like linear classifiers, the difference between a point and its projection onto the decision boundary can be viewed as the explanation. We then define the importance as the explanation weighted by the gradient of prediction $w.r.t$ the input, and identify biomarkers based on this importance measure. We perform a regression task to further validate our biomarker selection: compared to using all edges in the connectivity matrix, using the top 10\% important edges we generate a lower regression error on 6 different severity scores. Our experiments show that the invertible network is both effective at ASD classification and interpretable, allowing for discovery of reliable biomarkers.

Xiaoxiao Li, Nicha C. Dvornek, Yuan Zhou et al.

Finding the biomarkers associated with ASD is helpful for understanding the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatment. A promising approach to identify biomarkers is using Graph Neural Networks (GNNs), which can be used to analyze graph structured data, i.e. brain networks constructed by fMRI. One way to interpret important features is through looking at how the classification probability changes if the features are occluded or replaced. The major limitation of this approach is that replacing values may change the distribution of the data and lead to serious errors. Therefore, we develop a 2-stage pipeline to eliminate the need to replace features for reliable biomarker interpretation. Specifically, we propose an inductive GNN to embed the graphs containing different properties of task-fMRI for identifying ASD and then discover the brain regions/sub-graphs used as evidence for the GNN classifier. We first show GNN can achieve high accuracy in identifying ASD. Next, we calculate the feature importance scores using GNN and compare the interpretation ability with Random Forest. Finally, we run with different atlases and parameters, proving the robustness of the proposed method. The detected biomarkers reveal their association with social behaviors. We also show the potential of discovering new informative biomarkers. Our pipeline can be generalized to other graph feature importance interpretation problems.

Beibin Li, Sachin Mehta, Deepali Aneja et al.

In this paper, we introduce an end-to-end machine learning-based system for classifying autism spectrum disorder (ASD) using facial attributes such as expressions, action units, arousal, and valence. Our system classifies ASD using representations of different facial attributes from convolutional neural networks, which are trained on images in the wild. Our experimental results show that different facial attributes used in our system are statistically significant and improve sensitivity, specificity, and F1 score of ASD classification by a large margin. In particular, the addition of different facial attributes improves the performance of ASD classification by about 7% which achieves a F1 score of 76%.

Xiaoxiao Li, Nicha C. Dvornek, Yuan Zhou et al.

Discovering imaging biomarkers for autism spectrum disorder (ASD) is critical to help explain ASD and predict or monitor treatment outcomes. Toward this end, deep learning classifiers have recently been used for identifying ASD from functional magnetic resonance imaging (fMRI) with higher accuracy than traditional learning strategies. However, a key challenge with deep learning models is understanding just what image features the network is using, which can in turn be used to define the biomarkers. Current methods extract biomarkers, i.e., important features, by looking at how the prediction changes if "ignoring" one feature at a time. In this work, we go beyond looking at only individual features by using Shapley value explanation (SVE) from cooperative game theory. Cooperative game theory is advantageous here because it directly considers the interaction between features and can be applied to any machine learning method, making it a novel, more accurate way of determining instance-wise biomarker importance from deep learning models. A barrier to using SVE is its computational complexity: $2^N$ given $N$ features. We explicitly reduce the complexity of SVE computation by two approaches based on the underlying graph structure of the input data: 1) only consider the centralized coalition of each feature; 2) a hierarchical pipeline which first clusters features into small communities, then applies SVE in each community. Monte Carlo approximation can be used for large permutation sets. We first validate our methods on the MNIST dataset and compare to human perception. Next, to insure plausibility of our biomarker results, we train a Random Forest (RF) to classify ASD/control subjects from fMRI and compare SVE results to standard RF-based feature importance. Finally, we show initial results on ranked fMRI biomarkers using SVE on a deep learning classifier for the ASD/control dataset.

Xiaoxiao Li, Nicha C. Dvornek, Juntang Zhuang et al.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Finding the biomarkers associated with ASD is extremely helpful to understand the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatment. Although Deep Neural Networks (DNNs) have been applied in functional magnetic resonance imaging (fMRI) to identify ASD, understanding the data-driven computational decision making procedure has not been previously explored. Therefore, in this work, we address the problem of interpreting reliable biomarkers associated with identifying ASD; specifically, we propose a 2-stage method that classifies ASD and control subjects using fMRI images and interprets the saliency features activated by the classifier. First, we trained an accurate DNN classifier. Then, for detecting the biomarkers, different from the DNN visualization works in computer vision, we take advantage of the anatomical structure of brain fMRI and develop a frequency-normalized sampling method to corrupt images. Furthermore, in the ASD vs. control subjects classification scenario, we provide a new approach to detect and characterize important brain features into three categories. The biomarkers we found by the proposed method are robust and consistent with previous findings in the literature. We also validate the detected biomarkers by neurological function decoding and comparing with the DNN activation maps.

Nicha C. Dvornek, Daniel Yang, Archana Venkataraman et al.

Treating children with autism spectrum disorders (ASD) with behavioral interventions, such as Pivotal Response Treatment (PRT), has shown promise in recent studies. However, deciding which therapy is best for a given patient is largely by trial and error, and choosing an ineffective intervention results in loss of valuable treatment time. We propose predicting patient response to PRT from baseline task-based fMRI by the novel application of a random forest and tree bagging strategy. Our proposed learning pipeline uses random forest regression to determine candidate brain voxels that may be informative in predicting treatment response. The candidate voxels are then tested stepwise for inclusion in a bagged tree ensemble. After the predictive model is constructed, bias correction is performed to further increase prediction accuracy. Using data from 19 ASD children who underwent a 16 week trial of PRT and a leave-one-out cross-validation framework, the presented learning pipeline was tested against several standard methods and variations of the pipeline and resulted in the highest prediction accuracy.