Dynamic models in fMRI

Most statistical methods for assessing activated voxels in fMRI experiments are based on correlation or regression analysis. In this context the main assumptions are that the baseline can be described by a few known basis-functions or variables and that the effect of the stimulus, i.e. the activation, stays constant over time. As these assumptions are in many cases neither necessary nor correct, a new dynamic approach that does not depend on those suppositions will be presented. This allows for simultaneous nonparametric estimation of the baseline as well as the time-varying effect of stimulation. This method of estimating the stimulus related areas of the brain furthermore provides the possibility of an analysis of the temporal and spatial development of the activation within an fMRI-experiment

Increasing power for voxel-wise genome-wide association studies : the random field theory, least square kernel machines and fast permutation procedures

Imaging traits are thought to have more direct links to genetic variation than diagnostic measures based on cognitive or clinical assessments and provide a powerful substrate to examine the influence of genetics on human brains. Although imaging genetics has attracted growing attention and interest, most brain-wide genome-wide association studies focus on voxel-wise single-locus approaches, without taking advantage of the spatial information in images or combining the effect of multiple genetic variants. In this paper we present a fast implementation of voxel- and cluster-wise inferences based on the random field theory to fully use the spatial information in images. The approach is combined with a multi-locus model based on least square kernel machines to associate the joint effect of several single nucleotide polymorphisms (SNP) with imaging traits. A fast permutation procedure is also proposed which significantly reduces the number of permutations needed relative to the standard empirical method and provides accurate small p-value estimates based on parametric tail approximation. We explored the relation between 448,294 single nucleotide polymorphisms and 18,043 genes in 31,662 voxels of the entire brain across 740 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Structural MRI scans were analyzed using tensor-based morphometry (TBM) to compute 3D maps of regional brain volume differences compared to an average template image based on healthy elderly subjects. We find method to be more sensitive compared with voxel-wise single-locus approaches. A number of genes were identified as having significant associations with volumetric changes. The most associated gene was GRIN2B, which encodes the N-methyl-d-aspartate (NMDA) glutamate receptor NR2B subunit and affects both the parietal and temporal lobes in human brains. Its role in Alzheimer's disease has been widely acknowledged and studied, suggesting the validity of the approach. The various advantages over existing approaches indicate a great potential offered by this novel framework to detect genetic influences on human brains

Functional data analysis approaches for 3-dimensional brain images

Functional data analysis approaches for 3-dimensional brain images The analysis of brain images poses many challenges from a statistical perspective. First, these images are usually high-dimensional (sometimes millions of data points for each image), therefore a statistical analysis based on scalable techniques is often required. Second, these data exhibit clear spatial dependence due to the differences in structures and functions of the brain regions. Functional data analysis is a modern branch of statistics aimed at analysing data that are in the form of functions. Many tools from multivariate analysis and nonparametric smoothing are used in functional data analysis to reduce noise and perform dimension reduction. This thesis shows three applications of functional data analysis for large-scale 3-dimensional brain images, mainly focusing on prediction of scalar and imaging outcomes. A workflow for building prediction intervals for scalar outcomes from 3D covariates is devised and applied for the prediction of individual chronological age from brain anatomical images. Then, a framework for the analysis of functional data with spatially-dependent mean-variance relationship and skewness is described, with an application to structural imaging. At last, a functional imaging problem is studied: the prediction of a task-evoked response image from resting-state data is achieved through an image-on-image regression model. The results discussed in this thesis are mostly comparable with more complicated machine-learning approaches available in the literature, while being more easily interpretable and often more computationally appealing. Functional data analysis might represent a valid option for the statistical analysis of brain images even in high-dimensional setting

Resting state correlates of subdimensions of anxious affect

Resting state fMRI may help identify markers of risk for affective disorder. Given the comorbidity of anxiety and depressive disorders and the heterogeneity of these disorders as defined by DSM, an important challenge is to identify alterations in resting state brain connectivity uniquely associated with distinct profiles of negative affect. The current study aimed to address this by identifying differences in brain connectivity specifically linked to cognitive and physiological profiles of anxiety, controlling for depressed affect. We adopted a two-stage multivariate approach. Hierarchical clustering was used to independently identify dimensions of negative affective style and resting state brain networks. Combining the clustering results, we examined individual differences in resting state connectivity uniquely associated with subdimensions of anxious affect, controlling for depressed affect. Physiological and cognitive subdimensions of anxious affect were identified. Physiological anxiety was associated with widespread alterations in insula connectivity, including decreased connectivity between insula subregions and between the insula and other medial frontal and subcortical networks. This is consistent with the insula facilitating communication between medial frontal and subcortical regions to enable control of physiological affective states. Meanwhile, increased connectivity within a frontoparietal-posterior cingulate cortex-precunous network was specifically associated with cognitive anxiety, potentially reflecting increased spontaneous negative cognition (e.g., worry). These findings suggest that physiological and cognitive anxiety comprise subdimensions of anxiety-related affect and reveal associated alterations in brain connectivity

Multiscale adaptive smoothing models for the hemodynamic response function in fMRI

In the event-related functional magnetic resonance imaging (fMRI) data analysis, there is an extensive interest in accurately and robustly estimating the hemodynamic response function (HRF) and its associated statistics (e.g., the magnitude and duration of the activation). Most methods to date are developed in the time domain and they have utilized almost exclusively the temporal information of fMRI data without accounting for the spatial information. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) in the frequency domain by integrating the spatial and frequency information to adaptively and accurately estimate HRFs pertaining to each stimulus sequence across all voxels in a three-dimensional (3D) volume. We use two sets of simulation studies and a real data set to examine the finite sample performance of MASM in estimating HRFs. Our real and simulated data analyses confirm that MASM outperforms several other state-of-the-art methods, such as the smooth finite impulse response (sFIR) model.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS609 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Meta-analysis of functional neuroimaging data using Bayesian nonparametric binary regression

In this work we perform a meta-analysis of neuroimaging data, consisting of locations of peak activations identified in 162 separate studies on emotion. Neuroimaging meta-analyses are typically performed using kernel-based methods. However, these methods require the width of the kernel to be set a priori and to be constant across the brain. To address these issues, we propose a fully Bayesian nonparametric binary regression method to perform neuroimaging meta-analyses. In our method, each location (or voxel) has a probability of being a peak activation, and the corresponding probability function is based on a spatially adaptive Gaussian Markov random field (GMRF). We also include parameters in the model to robustify the procedure against miscoding of the voxel response. Posterior inference is implemented using efficient MCMC algorithms extended from those introduced in Holmes and Held [Bayesian Anal. 1 (2006) 145--168]. Our method allows the probability function to be locally adaptive with respect to the covariates, that is, to be smooth in one region of the covariate space and wiggly or even discontinuous in another. Posterior miscoding probabilities for each of the identified voxels can also be obtained, identifying voxels that may have been falsely classified as being activated. Simulation studies and application to the emotion neuroimaging data indicate that our method is superior to standard kernel-based methods.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS523 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Multivariate varying coefficient model for functional responses

Motivated by recent work studying massive imaging data in the neuroimaging literature, we propose multivariate varying coefficient models (MVCM) for modeling the relation between multiple functional responses and a set of covariates. We develop several statistical inference procedures for MVCM and systematically study their theoretical properties. We first establish the weak convergence of the local linear estimate of coefficient functions, as well as its asymptotic bias and variance, and then we derive asymptotic bias and mean integrated squared error of smoothed individual functions and their uniform convergence rate. We establish the uniform convergence rate of the estimated covariance function of the individual functions and its associated eigenvalue and eigenfunctions. We propose a global test for linear hypotheses of varying coefficient functions, and derive its asymptotic distribution under the null hypothesis. We also propose a simultaneous confidence band for each individual effect curve. We conduct Monte Carlo simulation to examine the finite-sample performance of the proposed procedures. We apply MVCM to investigate the development of white matter diffusivities along the genu tract of the corpus callosum in a clinical study of neurodevelopment.Comment: Published in at http://dx.doi.org/10.1214/12-AOS1045 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org