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

Task functional magnetic resonance imaging (fMRI) is a type of neuroimaging data used to identify areas of the brain that activate during specific tasks or stimuli. These data are conventionally modeled using a massive univariate approach across all data locations, which ignores spatial dependence at the cost of model power. We previously developed and validated a spatial Bayesian model leveraging dependencies along the cortical surface of the brain in order to improve accuracy and power. This model utilizes stochastic partial differential equation spatial priors with sparse precision matrices to allow for appropriate modeling of spatially-dependent activations seen in the neuroimaging literature, resulting in substantial increases in model power. Our original implementation relies on the computational efficiencies of the integrated nested Laplace approximation (INLA) to overcome the computational challenges of analyzing high-dimensional fMRI data while avoiding issues associated with variational Bayes implementations. However, this requires significant memory resources, extra software, and software licenses to run. In this article, we develop an exact Bayesian analysis method for the general linear model, employing an efficient expectation-maximization algorithm to find maximum a posteriori estimates of task-based regressors on cortical surface fMRI data. Through an extensive simulation study of cortical surface-based fMRI data, we compare our proposed method to the existing INLA implementation, as well as a conventional massive univariate approach employing ad-hoc spatial smoothing. We also apply the method to task fMRI data from the Human Connectome Project and show that our proposed implementation produces similar results to the validated INLA implementation. Both the INLA and EM-based implementations are available through our open-source BayesfMRI R package.Comment: 29 pages, 10 figures. arXiv admin note: text overlap with arXiv:2203.0005

A robust multivariate, non-parametric outlier identification method for scrubbing in fMRI

Functional magnetic resonance imaging (fMRI) data contain high levels of noise and artifacts. To avoid contamination of downstream analyses, fMRI-based studies must identify and remove these noise sources prior to statistical analysis. One common approach is the "scrubbing" of fMRI volumes that are thought to contain high levels of noise. However, existing scrubbing techniques are based on ad hoc measures of signal change. We consider scrubbing via outlier detection, where volumes containing artifacts are considered multidimensional outliers. Robust multivariate outlier detection methods are proposed using robust distances (RDs), which are related to the Mahalanobis distance. These RDs have a known distribution when the data are i.i.d. normal, and that distribution can be used to determine a threshold for outliers where fMRI data violate these assumptions. Here, we develop a robust multivariate outlier detection method that is applicable to non-normal data. The objective is to obtain threshold values to flag outlying volumes based on their RDs. We propose two threshold candidates that embark on the same two steps, but the choice of which depends on a researcher's purpose. Our main steps are dimension reduction and selection, robust univariate outlier imputation to get rid of the effect of outliers on the distribution, and estimating an outlier threshold based on the upper quantile of the RD distribution without outliers. The first threshold candidate is an upper quantile of the empirical distribution of RDs obtained from the imputed data. The second threshold candidate calculates the upper quantile of the RD distribution that a nonparametric bootstrap uses to account for uncertainty in the empirical quantile. We compare our proposed fMRI scrubbing method to motion scrubbing, data-driven scrubbing, and restrictive parametric multivariate outlier detection methods

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%.Comment: body 21 pages, 11 figure

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

Sources of residual autocorrelation in multiband task fMRI and strategies for effective mitigation

In task fMRI analysis, OLS is typically used to estimate task-induced activation in the brain. Since task fMRI residuals often exhibit temporal autocorrelation, it is common practice to perform prewhitening prior to OLS to satisfy the assumption of residual independence, equivalent to GLS. While theoretically straightforward, a major challenge in prewhitening in fMRI is accurately estimating the residual autocorrelation at each location of the brain. Assuming a global autocorrelation model, as in several fMRI software programs, may under- or over-whiten particular regions and fail to achieve nominal false positive control across the brain. Faster multiband acquisitions require more sophisticated models to capture autocorrelation, making prewhitening more difficult. These issues are becoming more critical now because of a trend towards subject-level analysis, where prewhitening has a greater impact than in group-average analyses. In this article, we first thoroughly examine the sources of residual autocorrelation in multiband task fMRI. We find that residual autocorrelation varies spatially throughout the cortex and is affected by the task, the acquisition method, modeling choices, and individual differences. Second, we evaluate the ability of different AR-based prewhitening strategies to effectively mitigate autocorrelation and control false positives. We find that allowing the prewhitening filter to vary spatially is the most important factor for successful prewhitening, even more so than increasing AR model order. To overcome the computational challenge associated with spatially variable prewhitening, we developed a computationally efficient R implementation based on parallelization and fast C++ backend code. This implementation is included in the open source R package BayesfMRI.Comment: 26 pages with 1 page of appendix, 11 figures with 1 figure of supplementary figur

A Bayesian General Linear Modeling Approach to Cortical Surface fMRI Data Analysis

Cortical surface functional magnetic resonance imaging (cs-fMRI) has recently grown in popularity versus traditional volumetric fMRI. In addition to offering better whole-brain visualization, dimension reduction, removal of extraneous tissue types, and improved alignment of cortical areas across subjects, it is also more compatible with common assumptions of Bayesian spatial models. However, as no spatial Bayesian model has been proposed for cs-fMRI data, most analyses continue to employ the classical general linear model (GLM), a “massive univariate” approach. Here, we propose a spatial Bayesian GLM for cs-fMRI, which employs a class of sophisticated spatial processes to model latent activation fields. We make several advances compared with existing spatial Bayesian models for volumetric fMRI. First, we use integrated nested Laplacian approximations, a highly accurate and efficient Bayesian computation technique, rather than variational Bayes. To identify regions of activation, we utilize an excursions set method based on the joint posterior distribution of the latent fields, rather than the marginal distribution at each location. Finally, we propose the first multi-subject spatial Bayesian modeling approach, which addresses a major gap in the existing literature. The methods are very computationally advantageous and are validated through simulation studies and two task fMRI studies from the Human Connectome Project. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement

BluePort: A Platform to Study the Eosinophilic Response of Mice to the Bite of a Vector of Leishmania Parasites, Lutzomyia longipalpis Sand Flies

transmission in residents of endemic areas has been attributed to the acquisition of immunity to sand fly salivary proteins. One theoretical way to accelerate the acquisition of this immunity is to increase the density of antigen-presenting cells at the sand fly bite site. Here we describe a novel tissue platform that can be used for this purpose. sand flies. Results presented indicate that a shift in the inflammatory response, from neutrophilic to eosinophilic, is the main histopathological feature associated with the immunity acquired through repeated exposure to the bite of sand flies, and that the BluePort tissue compartment could be used to accelerate this process. In addition, changes observed inside the BluePort parenchyma indicate that it could be used to study complex immunobiological processes, and to develop ectopic secondary lymphoid structures.Understanding the characteristics of the dermal response to the bite of sand flies is a critical element of strategies to control leishmaniasis using vaccines that target salivary proteins. Finding that dermal eosinophilia is such a prominent component of the anti-salivary immunity induced by repeated exposure to sand fly bites raises one important consideration: how to avoid the immunological conflict derived from a protective Th2-driven immunity directed to sand fly saliva with a protective Th1-driven immunity directed to the parasite. The BluePort platform is an ideal tool to address experimentally this conundrum

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation