PhD Dissertation Defense

Analysis of brain network connectivity
using spatial information

Sai Ma

1:00pm Thursday, 18 April 2013, ITE 325b

In current functional magnetic resonance imaging (fMRI) research, one of the most active areas involves exploring statistical dependencies among brain regions, known as functional connectivity analysis. Data-driven methods, especially independent component analysis (ICA), have been successfully applied to fMRI data to extract distributed brain networks and offer an opportunity to investigate functional connectivity on a network level, thus at a multivariate level. However, the independence assumption in ICA is neither necessarily nor typically satisfied in real applications and an extension is desirable. Furthermore, most current ICA-based studies focus on the use of temporal information and second-order statistics for functional connectivity analysis. Taking spatial information and higher-order statistics in fMRI data into account is expected to lead to better understanding of the overall brain network connectivity in healthy controls and also in patients with mental disorders, such as schizophrenia.

We develop a dependent component analysis (DCA) framework to generalize the ICA-based connectivity analysis methods by grouping components into maximally independent clusters. First, we define functional network connectivity as the statistical dependence among spatial components, instead of the typically used temporal correlation. Based on this definition, we use a hypothesis test to automatically generate functional connectivity structure for a large number of brain networks. After that, we separate dependent components within a given cluster using prior information, such as sparsity and experimental paradigm information, to achieve a better decomposition. We also combine this DCA-based clustering analysis with graph-theoretical analysis to discover significant group differences in topological properties of functional connectivity structure. To extend the methodologies currently available for functional connectivity, we propose an independent vector analysis (IVA) based scheme to extract and analyze dynamic functional connectivity.

The methods we develop offer advantages for effective and efficient examination of not only static, but also dynamic functional connectivity among different brain networks. We identify significant differences in functional connectivity structure between healthy controls and patients with schizophrenia, which may prove useful to serve as potential biomarkers for diagnosis. We also find task-induced modulations in functional connectivity when comparing different active states in the brain. Furthermore, we observe temporal variability in functional connectivity structure and physiologically meaningful group differences in dynamic connectivity among several brain networks. Our methods can provide insights to understanding of functional characteristics of the brain network organization in healthy individuals and patients with schizophrenia.

Committee: Dr. Adali (Chair), Dr. Morris, Dr. Rutledge, Dr. LaBerge, Dr. Phlypo, Dr. Calhoun, and Dr. Westlake