Semiparametric Estimation of Task-Based Dynamic Functional Connectivity on the Population Level

Dynamic functional connectivity (dFC) estimates time-dependent associations between pairs of brain region time series as typically acquired during functional MRI. dFC changes are most commonly quantified by pairwise correlation coefficients between the time series within a sliding window. Here, we applied a recently developed bootstrap-based technique (Kudela et al., 2017) to robustly estimate subject-level dFC and its confidence intervals in a task-based fMRI study (24 subjects who tasted their most frequently consumed beer and Gatorade as an appetitive control). We then combined information across subjects and scans utilizing semiparametric mixed models to obtain a group-level dFC estimate for each pair of brain regions, flavor, and the difference between flavors. The proposed approach relies on the estimated group-level dFC accounting for complex correlation structures of the fMRI data, multiple repeated observations per subject, experimental design, and subject-specific variability. It also provides condition-specific dFC and confidence intervals for the whole brain at the group level. As a summary dFC metric, we used the proportion of time when the estimated associations were either significantly positive or negative. For both flavors, our fully-data driven approach yielded regional associations that reflected known, biologically meaningful brain organization as shown in prior work, as well as closely resembled resting state networks (RSNs). Specifically, beer flavor-potentiated associations were detected between several reward-related regions, including the right ventral striatum (VST), lateral orbitofrontal cortex, and ventral anterior insular cortex (vAIC). The enhancement of right VST-vAIC association by a taste of beer independently validated the main activation-based finding (Oberlin et al., 2016). Most notably, our novel dFC methodology uncovered numerous associations undetected by the traditional static FC analysis. The data-driven, novel dFC methodology presented here can be used for a wide range of task-based fMRI designs to estimate the dFC at multiple levels-group-, individual-, and task-specific, utilizing a combination of well-established statistical methods

Dynamic Thermal Imaging for Intraoperative Monitoring of Neuronal Activity and Cortical Perfusion

Neurosurgery is a demanding medical discipline that requires a complex interplay of several neuroimaging techniques. This allows structural as well as functional information to be recovered and then visualized to the surgeon. In the case of tumor resections this approach allows more fine-grained differentiation of healthy and pathological tissue which positively influences the postoperative outcome as well as the patient's quality of life. In this work, we will discuss several approaches to establish thermal imaging as a novel neuroimaging technique to primarily visualize neural activity and perfusion state in case of ischaemic stroke. Both applications require novel methods for data-preprocessing, visualization, pattern recognition as well as regression analysis of intraoperative thermal imaging. Online multimodal integration of preoperative and intraoperative data is accomplished by a 2D-3D image registration and image fusion framework with an average accuracy of 2.46 mm. In navigated surgeries, the proposed framework generally provides all necessary tools to project intraoperative 2D imaging data onto preoperative 3D volumetric datasets like 3D MR or CT imaging. Additionally, a fast machine learning framework for the recognition of cortical NaCl rinsings will be discussed throughout this thesis. Hereby, the standardized quantification of tissue perfusion by means of an approximated heating model can be achieved. Classifying the parameters of these models yields a map of connected areas, for which we have shown that these areas correlate with the demarcation caused by an ischaemic stroke segmented in postoperative CT datasets. Finally, a semiparametric regression model has been developed for intraoperative neural activity monitoring of the somatosensory cortex by somatosensory evoked potentials. These results were correlated with neural activity of optical imaging. We found that thermal imaging yields comparable results, yet doesn't share the limitations of optical imaging. In this thesis we would like to emphasize that thermal imaging depicts a novel and valid tool for both intraoperative functional and structural neuroimaging

Improving the accuracy of brain activation maps in the group-level analysis of fMRI data utilizing spatiotemporal Gaussian process model

OBJECTIVE: Accuracy and precision of the statistical analysis methods used for brain activation maps are essential. Adjusting models to consider spatiotemporal correlation embedded in fMRI data may increase their accuracy, but it also introduces a high computational cost. The present study aimed to apply and assess the spatiotemporal Gaussian process (STGP) model to improve accuracy and reduce cost. METHODS: We applied the spatiotemporal Gaussian process (STGP) model for both simulated and experimental memory tfMRI data and compared the findings with fast, fully Bayesian, and General Linear Models (GLM). To assess their accuracy and precision, the models were fitted to the simulated data (1000 voxels,100 times point for 50 people), and an average of accuracy indexes of 100 repetitions was computed. Functional and activation maps for all models were calculated in experimental data analysis. RESULTS: STGP model resulted in a higher Z-score in the whole brain, in the 1000 most activated voxels, and in the frontal lobe as the approved memory area. Based on the simulated data, the STGP model showed more accuracy and precision than the other two models. However, its computational time was more than the GLM, as the price of model correction, but much less than that of the fast, fully Bayesian model. CONCLUSION: Spatiotemporal correlation further improved the accuracy of the STGP compared to the GLM and fast, fully Bayesian model. This can result in more accurate activation maps. Moreover, the STGP model’s computational speed appears to be reasonable for model application

Interpretable statistics for complex modelling: quantile and topological learning

As the complexity of our data increased exponentially in the last decades, so has our need for interpretable features. This thesis revolves around two paradigms to approach this quest for insights. In the first part we focus on parametric models, where the problem of interpretability can be seen as a “parametrization selection”. We introduce a quantile-centric parametrization and we show the advantages of our proposal in the context of regression, where it allows to bridge the gap between classical generalized linear (mixed) models and increasingly popular quantile methods. The second part of the thesis, concerned with topological learning, tackles the problem from a non-parametric perspective. As topology can be thought of as a way of characterizing data in terms of their connectivity structure, it allows to represent complex and possibly high dimensional through few features, such as the number of connected components, loops and voids. We illustrate how the emerging branch of statistics devoted to recovering topological structures in the data, Topological Data Analysis, can be exploited both for exploratory and inferential purposes with a special emphasis on kernels that preserve the topological information in the data. Finally, we show with an application how these two approaches can borrow strength from one another in the identification and description of brain activity through fMRI data from the ABIDE project

Statistical methods for high-dimensional data with complex correlation structure applied to the brain dynamic functional connectivity studyDY

Indiana University-Purdue University Indianapolis (IUPUI)A popular non-invasive brain activity measurement method is based on the functional magnetic resonance imaging (fMRI). Such data are frequently used to study functional connectivity (FC) defined as statistical association among two or more anatomically distinct fMRI signals (Friston, 1994). FC has emerged in recent years as a valuable tool for providing a deeper understanding of neurodegenerative diseases and neuropsychiatric disorders, such as Alzheimer's disease and autism. Information about complex association structure in high-dimensional fMRI data is often discarded by a calculating an average across complex spatiotemporal processes without providing an uncertainty measure around it. First, we propose a non-parametric approach to estimate the uncertainty of dynamic FC (dFC) estimates. Our method is based on three components: an extension of a boot strapping method for multivariate time series, recently introduced by Jentsch and Politis (2015); sliding window correlation estimation; and kernel smoothing. Second, we propose a two-step approach to analyze and summarize dFC estimates from a task-based fMRI study of social-to-heavy alcohol drinkers during stimulation with avors. In the first step, we apply our method from the first paper to estimate dFC for each region subject combination. In the second step, we use semiparametric additive mixed models to account for complex correlation structure and model dFC on a population level following the study's experimental design. Third, we propose to utilize the estimated dFC to study the system's modularity defined as the mutually exclusive division of brain regions into blocks with intra-connectivity greater than the one obtained by chance. As a result, we obtain brain partition suggesting the existence of common functionally-based brain organization. The main contribution of our work stems from the combination of the methods from the fields of statistics, machine learning and network theory to provide statistical tools for studying brain connectivity from a holistic, multi-disciplinary perspective

Predicting Responses from Weighted Networks with Node Covariates in an Application to Neuroimaging

We consider the setting where many networks are observed on a common node set, and each observation comprises edge weights of a network, covariates observed at each node, and an overall response. The goal is to use the edge weights and node covariates to predict the response while identifying an interpretable set of predictive features. Our motivating application is neuroimaging, where edge weights encode functional connectivity measured between brain regions, node covariates encode task activations at each brain region, and the response is disease status or score on a behavioral task. We propose an approach that constructs feature groups based on assumed community structure (naturally occurring in neuroimaging applications). We propose two feature grouping schemes that incorporate both edge weights and node covariates, and we derive algorithms for optimization using an overlapping group LASSO penalty. Empirical results on synthetic data show that our method, relative to competing approaches, has similar or improved prediction error along with superior support recovery, enabling a more interpretable and potentially more accurate understanding of the underlying process. We also apply the method to neuroimaging data from the Human Connectome Project. Our approach is widely applicable in neuroimaging where interpretability is highly desired

Bayesian inference for group-level cortical surface image-on-scalar-regression with Gaussian process priors

In regression-based analyses of group-level neuroimage data researchers typically fit a series of marginal general linear models to image outcomes at each spatially-referenced pixel. Spatial regularization of effects of interest is usually induced indirectly by applying spatial smoothing to the data during preprocessing. While this procedure often works well, resulting inference can be poorly calibrated. Spatial modeling of effects of interest leads to more powerful analyses, however the number of locations in a typical neuroimage can preclude standard computation with explicitly spatial models. Here we contribute a Bayesian spatial regression model for group-level neuroimaging analyses. We induce regularization of spatially varying regression coefficient functions through Gaussian process priors. When combined with a simple nonstationary model for the error process, our prior hierarchy can lead to more data-adaptive smoothing than standard methods. We achieve computational tractability through Vecchia approximation of our prior which, critically, can be constructed for a wide class of spatial correlation functions and results in prior models that retain full spatial rank. We outline several ways to work with our model in practice and compare performance against standard vertex-wise analyses. Finally we illustrate our method in an analysis of cortical surface fMRI task contrast data from a large cohort of children enrolled in the Adolescent Brain Cognitive Development study