Electroencephalography/Magnetoencephalography (EEG/MEG) source localization involves the estimation of neural activity inside the brain volume that underlies the EEG/MEG measures observed at the sensor array. In this paper, we consider a Bayesian finite spatial mixture model for source reconstruction and implement Ant Colony System (ACS) optimization coupled with Iterated Conditional Modes (ICM) for computing estimates of the neural source activity. Our approach is evaluated using simulation studies and a real data application in which we implement a nonparametric bootstrap for interval estimation. We demonstrate improved performance of the ACS-ICM algorithm as compared to existing methodology for the same spatiotemporal model.
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 and mild cognitive impairment. 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 which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. 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). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.
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 and mild cognitive impairment. 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 examine longitudinal data in both a 4-region and an 8-region network and relate longitudinal effective brain connectivity networks estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both networks we find evidence of potential association between the connectivity of several DMN regions and SNPs lying in the disease-constrained set.
In a host of business applications, biomedical and epidemiological studies, the problem of multicollinearity among predictor variables is a frequent issue in longitudinal data analysis for linear mixed models (LMM). We consider an efficient estimation strategy for high-dimensional data application, where the dimensions of the parameters are larger than the number of observations. In this paper, we are interested in estimating the fixed effects parameters of the LMM when it is assumed that some prior information is available in the form of linear restrictions on the parameters. We propose the pretest and shrinkage estimation strategies using the ridge full model as the base estimator. We establish the asymptotic distributional bias and risks of the suggested estimators and investigate their relative performance with respect to the ridge full model estimator. Furthermore, we compare the numerical performance of the LASSO-type estimators with the pretest and shrinkage ridge estimators. The methodology is investigated using simulation studies and then demonstrated on an application exploring how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease.
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