This thesis presents research focused on developing statistical methods with emphasis on techniques that can be used for the analysis of data in imaging studies and sparse estimations for applications in high-dimensional data. The first contribution addresses the pixel/voxel-labeling problem for spatial hidden Markov models in image analysis. We formulate a Gaussian spatial mixture model with Potts model used as a prior for mixture allocations for the latent states in the model. Jointly estimating the model parameters, the discrete state variables and the number of states (number of mixture components) is recognized as a difficult combinatorial optimization. To overcome drawbacks associated with local algorithms, we implement and make comparisons between iterated conditional modes (ICM), simulated annealing (SA) and hybrid ICM with ant colony system (ACS-ICM) optimization for pixel labelling, parameter estimation and mixture component estimation. In the second contribution, we develop ACS-ICM algorithm for spatiotemporal modeling of combined MEG/EEG data for computing estimates of the neural source activity. We consider a Bayesian finite spatial mixture model with a Potts model as a spatial prior and implement the ACS-ICM for simultaneous point estimation and model selection for the number of mixture components. Our approach is evaluated using simulation studies and an application examining the visual response to scrambled faces. In addition, we develop a nonparametric bootstrap for interval estimation to account for uncertainty in the point estimates. In the third contribution, we present sparse estimation strategies in linear mixed model (LMM) for longitudinal data. We address the problem of estimating the fixed effects parameters of the LMM when the model is sparse and predictors are correlated. We propose and derive the asymptotic properties of the pretest and shrinkage estimation strategies. Simulation studies is performed to compare the numerical performance of the Lasso and adaptive Lasso estimators with the pretest and shrinkage ridge estimators. The methodology is evaluated through an application of a high-dimensional data examining effective brain connectivity and genetics. In the fourth and final contribution, we conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). / Graduate