arXiv subjects

Mary Beth Nebel

Publications and source records attributed to Mary Beth Nebel.

18 recordsLinked to original sources

arXiv2026

Bayesian brain mapping: a population-informed framework for personalized functional network topography and connectivity

The spatial topography of functional brain organization is increasingly recognized to play an important role in cognition and disease. Accounting for individual differences in functional topography is also crucial for accurately distinguishing spatial and temporal aspects of functional brain connectivity. Yet, accurate estimation of personalized functional brain networks from functional magnetic resonance imaging (fMRI) without extensive scanning remains challenging due to high noise levels. Here, we describe Bayesian Brain Mapping (BBM), a technique for personalized functional topography and connectivity informed by population information. BBM relies on population-derived priors on both spatial topography of networks and between-network functional connectivity to guide subject-level estimation and combat noise. These priors are based on existing spatial templates, such as parcellations or continuous network maps, providing correspondence to those templates. Yet BBM is highly flexible, avoiding strong spatial or temporal constraints and allowing for overlap between networks and heterogeneous patterns of engagement. BBM is designed for single-subject analysis, making it computationally efficient and translatable to clinical settings. Here, we describe the BBM model and illustrate the use of the BayesBrainMap R package to construct population-derived priors, fit the model, and perform inference to identify engagements. A demo is provided in an accompanying Github repo. We also share priors derived from the Human Connectome Project and provide code to support the construction of priors from different data sources, lowering the barrier to adoption of BBM for studies of individual brain organization.

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arXiv2024

A Deep-Generative Hybrid Model to Integrate Multimodal and Dynamic Connectivity for Predicting Spectrum-Level Deficits in Autism

We propose an integrated deep-generative framework, that jointly models complementary information from resting-state functional MRI (rs-fMRI) connectivity and diffusion tensor imaging (DTI) tractography to extract predictive biomarkers of a disease. The generative part of our framework is a structurally-regularized Dynamic Dictionary Learning (sr-DDL) model that decomposes the dynamic rs-fMRI correlation matrices into a collection of shared basis networks and time varying patient-specific loadings. This matrix factorization is guided by the DTI tractography matrices to learn anatomically informed connectivity profiles. The deep part of our framework is an LSTM-ANN block, which models the temporal evolution of the patient sr-DDL loadings to predict multidimensional clinical severity. Our coupled optimization procedure collectively estimates the basis networks, the patient-specific dynamic loadings, and the neural network weights. We validate our framework on a multi-score prediction task in 57 patients diagnosed with Autism Spectrum Disorder (ASD). Our hybrid model outperforms state-of-the-art baselines in a five-fold cross validated setting and extracts interpretable multimodal neural signatures of brain dysfunction in ASD.

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arXiv2024

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

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

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arXiv2024

A Joint Network Optimization Framework to Predict Clinical Severity from Resting State Functional MRI Data

We propose a novel optimization framework to predict clinical severity from resting state fMRI (rs-fMRI) data. Our model consists of two coupled terms. The first term decomposes the correlation matrices into a sparse set of representative subnetworks that define a network manifold. These subnetworks are modeled as rank-one outer-products which correspond to the elemental patterns of co-activation across the brain; the subnetworks are combined via patient-specific non-negative coefficients. The second term is a linear regression model that uses the patient-specific coefficients to predict a measure of clinical severity. We validate our framework on two separate datasets in a ten fold cross validation setting. The first is a cohort of fifty-eight patients diagnosed with Autism Spectrum Disorder (ASD). The second dataset consists of sixty three patients from a publicly available ASD database. Our method outperforms standard semi-supervised frameworks, which employ conventional graph theoretic and statistical representation learning techniques to relate the rs-fMRI correlations to behavior. In contrast, our joint network optimization framework exploits the structure of the rs-fMRI correlation matrices to simultaneously capture group level effects and patient heterogeneity. Finally, we demonstrate that our proposed framework robustly identifies clinically relevant networks characteristic of ASD.

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arXiv2024

Integrating Neural Networks and Dictionary Learning for Multidimensional Clinical Characterizations from Functional Connectomics Data

We propose a unified optimization framework that combines neural networks with dictionary learning to model complex interactions between resting state functional MRI and behavioral data. The dictionary learning objective decomposes patient correlation matrices into a collection of shared basis networks and subject-specific loadings. These subject-specific features are simultaneously input into a neural network that predicts multidimensional clinical information. Our novel optimization framework combines the gradient information from the neural network with that of a conventional matrix factorization objective. This procedure collectively estimates the basis networks, subject loadings, and neural network weights most informative of clinical severity. We evaluate our combined model on a multi-score prediction task using 52 patients diagnosed with Autism Spectrum Disorder (ASD). Our integrated framework outperforms state-of-the-art methods in a ten-fold cross validated setting to predict three different measures of clinical severity.

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arXiv2023

Less is more: balancing noise reduction and data retention in fMRI with data-driven scrubbing

Artifacts in functional MRI (fMRI) data cause deviations from common distributional assumptions, introduce spatial and temporal outliers, and reduce the signal-to-noise ratio of the data -- all of which can have negative consequences for downstream statistical analysis. Scrubbing is a technique for excluding fMRI volumes thought to be contaminated by artifacts and generally comes in two flavors. Motion scrubbing based on subject head motion-derived measures is popular but suffers from a number of drawbacks, especially high rates of censoring of individual volumes and entire subjects. Alternatively, data-driven scrubbing methods like DVARS are based on observed noise in the processed fMRI timeseries and may avoid some of these issues. Here we propose "projection scrubbing", a novel data-driven scrubbing method based on a statistical outlier detection framework and strategic dimension reduction, including independent component analysis (ICA), to isolate artifactual variation. We undertake a comprehensive comparison of motion scrubbing with data-driven projection scrubbing and DVARS. We argue that an appropriate metric for the success of scrubbing is maximal data retention subject to reasonable performance on typical benchmarks of functional connectivity. We find that stringent motion scrubbing yields worsened validity, worsened reliability, and produced small improvements to fingerprinting. Meanwhile, data-driven scrubbing methods tend to yield greater improvements to fingerprinting while not generally worsening validity or reliability. Importantly, however, data-driven scrubbing excludes a fraction of the number of volumes or entire sessions compared to motion scrubbing. The ability of data-driven fMRI scrubbing to improve data retention without negatively impacting the quality of downstream analysis has major implications for sample sizes in population neuroscience research.

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arXiv2022

Fast Bayesian estimation of brain activation with cortical surface and subcortical fMRI data using EM

Analysis of brain imaging scans is critical to understanding the way the human brain functions, which can be leveraged to treat injuries and conditions that affect the quality of life for a significant portion of the human population. In particular, functional magnetic resonance imaging (fMRI) scans give detailed data on a living subject at high spatial and temporal resolutions. Due to the high cost involved in the collection of these scans, robust methods of analysis are of critical importance in order to produce meaningful inference. Bayesian methods in particular allow for the inclusion of expected behavior from prior study into an analysis, increasing the power of the results while circumventing problems that arise in classical analyses, including the effects of smoothing results and sensitivity to multiple comparison testing corrections. Recent development of a surface-based spatial Bayesian general linear model for cortical surface fMRI (cs-fMRI) data provides the desired power increase in task fMRI data using stochastic partial differential equation (SPDE) priors. This model relies on the computational efficiencies of the integrated nested Laplace approximation (INLA) to perform powerful analyses that have been validated to outperform classical analyses. In this article, we develop an exact Bayesian analysis method for the GLM, employing an expectation-maximization (EM) algorithm to find maximum a posteriori (MAP) estimates of task-based regressors on cs-fMRI and subcortical fMRI data while using minimal computational resources. Our proposed method is compared to the INLA implementation of the Bayesian GLM, as well as a classical GLM on simulated data. A validation of the method on data from the Human Connectome Project is also provided.

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arXiv2021

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

We propose a novel matrix autoencoder to map functional connectomes from resting state fMRI (rs-fMRI) to structural connectomes from Diffusion Tensor Imaging (DTI), as guided by subject-level phenotypic measures. Our specialized autoencoder infers a low dimensional manifold embedding for the rs-fMRI correlation matrices that mimics a canonical outer-product decomposition. The embedding is simultaneously used to reconstruct DTI tractography matrices via a second manifold alignment decoder and to predict inter-subject phenotypic variability via an artificial neural network. We validate our framework on a dataset of 275 healthy individuals from the Human Connectome Project database and on a second clinical dataset consisting of 57 subjects with Autism Spectrum Disorder. We demonstrate that the model reliably recovers structural connectivity patterns across individuals, while robustly extracting predictive and interpretable brain biomarkers in a cross-validated setting. Finally, our framework outperforms several baselines at predicting behavioral phenotypes in both real-world datasets.

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arXiv2021

Group Linear non-Gaussian Component Analysis with Applications to Neuroimaging

Independent component analysis (ICA) is an unsupervised learning method popular in functional magnetic resonance imaging (fMRI). Group ICA has been used to search for biomarkers in neurological disorders including autism spectrum disorder and dementia. However, current methods use a principal component analysis (PCA) step that may remove low-variance features. Linear non-Gaussian component analysis (LNGCA) enables simultaneous dimension reduction and feature estimation including low-variance features in single-subject fMRI. We present a group LNGCA model to extract group components shared by more than one subject and subject-specific components. To determine the total number of components in each subject, we propose a parametric resampling test that samples spatially correlated Gaussian noise to match the spatial dependence observed in data. In simulations, our estimated group components achieve higher accuracy compared to group ICA. We apply our method to a resting-state fMRI study on autism spectrum disorder in 342 children (252 typically developing, 90 with autism), where the group signals include resting-state networks. We find examples of group components that appear to exhibit different levels of temporal engagement in autism versus typically developing children, as revealed using group LNGCA. This novel approach to matrix decomposition is a promising direction for feature detection in neuroimaging.

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arXiv2020

Neuropsychiatric Disease Classification Using Functional Connectomics -- Results of the Connectomics in NeuroImaging Transfer Learning Challenge

Large, open-source consortium datasets have spurred the development of new and increasingly powerful machine learning approaches in brain connectomics. However, one key question remains: are we capturing biologically relevant and generalizable information about the brain, or are we simply overfitting to the data? To answer this, we organized a scientific challenge, the Connectomics in NeuroImaging Transfer Learning Challenge (CNI-TLC), held in conjunction with MICCAI 2019. CNI-TLC included two classification tasks: (1) diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) within a pre-adolescent cohort; and (2) transference of the ADHD model to a related cohort of Autism Spectrum Disorder (ASD) patients with an ADHD comorbidity. In total, 240 resting-state fMRI time series averaged according to three standard parcellation atlases, along with clinical diagnosis, were released for training and validation (120 neurotypical controls and 120 ADHD). We also provided demographic information of age, sex, IQ, and handedness. A second set of 100 subjects (50 neurotypical controls, 25 ADHD, and 25 ASD with ADHD comorbidity) was used for testing. Models were submitted in a standardized format as Docker images through ChRIS, an open-source image analysis platform. Utilizing an inclusive approach, we ranked the methods based on 16 different metrics. The final rank was calculated using the rank product for each participant across all measures. Furthermore, we assessed the calibration curves of each method. Five participants submitted their model for evaluation, with one outperforming all other methods in both ADHD and ASD classification. However, further improvements are needed to reach the clinical translation of functional connectomics. We are keeping the CNI-TLC open as a publicly available resource for developing and validating new classification methodologies in the field of connectomics.

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arXiv2020

A Coupled Manifold Optimization Framework to Jointly Model the Functional Connectomics and Behavioral Data Spaces

The problem of linking functional connectomics to behavior is extremely challenging due to the complex interactions between the two distinct, but related, data domains. We propose a coupled manifold optimization framework which projects fMRI data onto a low dimensional matrix manifold common to the cohort. The patient specific loadings simultaneously map onto a behavioral measure of interest via a second, non-linear, manifold. By leveraging the kernel trick, we can optimize over a potentially infinite dimensional space without explicitly computing the embeddings. As opposed to conventional manifold learning, which assumes a fixed input representation, our framework directly optimizes for embedding directions that predict behavior. Our optimization algorithm combines proximal gradient descent with the trust region method, which has good convergence guarantees. We validate our framework on resting state fMRI from fifty-eight patients with Autism Spectrum Disorder using three distinct measures of clinical severity. Our method outperforms traditional representation learning techniques in a cross validated setting, thus demonstrating the predictive power of our coupled objective.

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arXiv2020

A spatial template independent component analysis model for subject-level brain network estimation and inference

Independent component analysis is commonly applied to functional magnetic resonance imaging (fMRI) data to extract independent components (ICs) representing functional brain networks. While ICA produces reliable group-level estimates, single-subject ICA often produces noisy results. Template ICA (tICA) is a hierarchical ICA model using empirical population priors to produce reliable subject-level IC estimates. However, this and other hierarchical ICA models assume unrealistically that subject effects are spatially independent. Here, we propose spatial template ICA (stICA), which incorporates spatial process priors into tICA. This results in greater estimation efficiency of ICs and subject effects. Additionally, the joint posterior distribution can be used to identify engaged areas using an excursions set approach. By leveraging spatial dependencies and avoiding massive multiple comparisons, stICA has high power to detect true effects. We derive an efficient expectation-maximization algorithm to obtain maximum likelihood estimates of the model parameters and posterior moments of the latent fields. Based on analysis of simulated data and fMRI data from the Human Connectome Project, we find that stICA produces estimates that are more accurate and reliable than benchmark approaches, and identifies larger and more reliable areas of engagement. The algorithm is quite tractable, achieving convergence within 7 hours in our fMRI analysis.

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arXiv2019

Template Independent Component Analysis: Targeted and Reliable Estimation of Subject-level Brain Networks using Big Data Population Priors

Large brain imaging databases contain a wealth of information on brain organization in the populations they target, and on individual variability. While such databases have been used to study group-level features of populations directly, they are currently underutilized as a resource to inform single-subject analysis. Here, we propose leveraging the information contained in large functional magnetic resonance imaging (fMRI) databases by establishing population priors to employ in an empirical Bayesian framework. We focus on estimation of brain networks as source signals in independent component analysis (ICA). We formulate a hierarchical "template" ICA model where source signals---including known population brain networks and subject-specific signals---are represented as latent variables. For estimation, we derive an expectation maximization (EM) algorithm having an explicit solution. However, as this solution is computationally intractable, we also consider an approximate subspace algorithm and a faster two-stage approach. Through extensive simulation studies, we assess performance of both methods and compare with dual regression, a popular but ad-hoc method. The two proposed algorithms have similar performance, and both dramatically outperform dual regression. We also conduct a reliability study utilizing the Human Connectome Project and find that template ICA achieves substantially better performance than dual regression, achieving 75-250% higher intra-subject reliability.

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arXiv2018

A Generative-Discriminative Basis Learning Framework to Predict Clinical Severity from Resting State Functional MRI Data

We propose a matrix factorization technique that decomposes the resting state fMRI (rs-fMRI) correlation matrices for a patient population into a sparse set of representative subnetworks, as modeled by rank one outer products. The subnetworks are combined using patient specific non-negative coefficients; these coefficients are also used to model, and subsequently predict the clinical severity of a given patient via a linear regression. Our generative-discriminative framework is able to exploit the structure of rs-fMRI correlation matrices to capture group level effects, while simultaneously accounting for patient variability. We employ ten fold cross validation to demonstrate the predictive power of our model on a cohort of fifty eight patients diagnosed with Autism Spectrum Disorder. Our method outperforms classical semi-supervised frameworks, which perform dimensionality reduction on the correlation features followed by non-linear regression to predict the clinical scores.

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arXiv2016

PCA leverage: outlier detection for high-dimensional functional magnetic resonance imaging data

Outlier detection for high-dimensional (HD) data is a popular topic in modern statistical research. However, one source of HD data that has received relatively little attention is functional magnetic resonance images (fMRI), which consists of hundreds of thousands of measurements sampled at hundreds of time points. At a time when the availability of fMRI data is rapidly growing---primarily through large, publicly available grassroots datasets---automated quality control and outlier detection methods are greatly needed. We propose PCA leverage and demonstrate how it can be used to identify outlying time points in an fMRI run. Furthermore, PCA leverage is a measure of the influence of each observation on the estimation of principal components, which are often of interest in fMRI data. We also propose an alternative measure, PCA robust distance, which is less sensitive to outliers and has controllable statistical properties. The proposed methods are validated through simulation studies and are shown to be highly accurate. We also conduct a reliability study using resting-state fMRI data from the Autism Brain Imaging Data Exchange and find that removal of outliers using the proposed methods results in more reliable estimation of subject-level resting-state networks using ICA.

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arXiv2016

Effects of Scan Length and Shrinkage on Reliability of Resting-State Functional Connectivity in the Human Connectome Project

In this paper, we use data from the Human Connectome Project (N=461) to investigate the effect of scan length on reliability of resting-state functional connectivity (rsFC) estimates produced from resting-state functional magnetic resonance imaging (rsfMRI). Additionally, we study the benefits of empirical Bayes shrinkage, in which subject-level estimates borrow strength from the population average by trading a small increase in bias for a greater reduction in variance. For each subject, we compute raw and shrinkage estimates of rsFC between 300 regions identified through independent components analysis (ICA) based on rsfMRI scans varying from 3 to 30 minutes in length. The time course for each region is determined using dual regression, and rsFC is estimated as the Pearson correlation between each pair of time courses. Shrinkage estimates for each subject are computed as a weighted average between the raw subject-level estimate and the population average estimate, where the weight is determined for each connection by the relationship of within-subject variance to between-subject variance. We find that shrinkage estimates exhibit greater reliability than raw estimates for most connections, with 30-40% improvement using scans less than 10 minutes in length and 10-20% improvement using scans of 20-30 minutes. We also observe significant spatial variability in reliability of both raw and shrinkage estimates, with connections within the default mode and motor networks exhibiting the greatest reliability and between-network connections exhibiting the poorest reliability. We conclude that the scan length required for reliable estimation of rsFC depends on the specific connections of interest, and shrinkage can be used to increase reliability of rsFC, even when produced from long, high-quality rsfMRI scans.

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arXiv2015

Improving Reliability of Subject-Level Resting-State fMRI Parcellation with Shrinkage Estimators

A recent interest in resting state functional magnetic resonance imaging (rsfMRI) lies in subdividing the human brain into anatomically and functionally distinct regions of interest. For example, brain parcellation is often used for defining the network nodes in connectivity studies. While inference has traditionally been performed on group-level data, there is a growing interest in parcellating single subject data. However, this is difficult due to the low signal-to-noise ratio of rsfMRI data, combined with typically short scan lengths. A large number of brain parcellation approaches employ clustering, which begins with a measure of similarity or distance between voxels. The goal of this work is to improve the reproducibility of single-subject parcellation using shrinkage estimators of such measures, allowing the noisy subject-specific estimator to "borrow strength" in a principled manner from a larger population of subjects. We present several empirical Bayes shrinkage estimators and outline methods for shrinkage when multiple scans are not available for each subject. We perform shrinkage on raw intervoxel correlation estimates and use both raw and shrinkage estimates to produce parcellations by performing clustering on the voxels. Our proposed method is agnostic to the choice of clustering method and can be used as a pre-processing step for any clustering algorithm. Using two datasets---a simulated dataset where the true parcellation is known and is subject-specific and a test-retest dataset consisting of two 7-minute rsfMRI scans from 20 subjects---we show that parcellations produced from shrinkage correlation estimates have higher reliability and validity than those produced from raw estimates. Application to test-retest data shows that using shrinkage estimators increases the reproducibility of subject-specific parcellations of the motor cortex by up to 30%.

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arXiv2013

Homotopic Group ICA for Multi-Subject Brain Imaging Data

Independent Component Analysis (ICA) is a computational technique for revealing latent factors that underlie sets of measurements or signals. It has become a standard technique in functional neuroimaging. In functional neuroimaging, so called group ICA (gICA) seeks to identify and quantify networks of correlated regions across subjects. This paper reports on the development of a new group ICA approach, Homotopic Group ICA (H-gICA), for blind source separation of resting state functional magnetic resonance imaging (fMRI) data. Resting state brain functional homotopy is the similarity of spontaneous fluctuations between bilaterally symmetrically opposing regions (i.e. those symmetric with respect to the mid-sagittal plane) (Zuo et al., 2010). The approach we proposed improves network estimates by leveraging this known brain functional homotopy. H-gICA increases the potential for network discovery, effectively by averaging information across hemispheres. It is theoretically proven to be identical to standard group ICA when the true sources are both perfectly homotopic and noise-free, while simulation studies and data explorations demonstrate its benefits in the presence of noise. Moreover, compared to commonly applied group ICA algorithms, the structure of the H-gICA input data leads to significant improvement in computational efficiency. A simulation study comfirms its effectiveness in homotopic, non-homotopic and mixed settings, as well as on the landmark ADHD-200 dataset. From a relatively small subset of data, several brain networks were found including: the visual, the default mode and auditory networks, as well as others. These were shown to be more contiguous and clearly delineated than the corresponding ordinary group ICA. Finally, in addition to improving network estimation, H-gICA facilitates the investigation of functional homotopy via ICA-based networks.

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