Doctor of Philosophy

dissertationThe human brain is the seat of cognition and behavior. Understanding the brain mechanistically is essential for appreciating its linkages with cognitive processes and behavioral outcomes in humans. Mechanisms of brain function categorically represent rich and widely under-investigated biological substrates for neural-driven studies of psychiatry and mental health. Research examining intrinsic connectivity patterns across whole brain systems utilizes functional magnetic resonance imaging (fMRI) to trace spontaneous fluctuations in blood oxygen-level dependent (BOLD) signals. In the first study presented, we reveal patterns of dynamic attractors in resting state functional connectivity data corresponding to well-documented biological networks. We introduce a novel simulation for whole brain dynamics that can be adapted to either group-level analysis or single-subject level models. We describe stability of intrinsic functional architecture in terms of transient and global steady states resembling biological networks. In the second study, we demonstrate plasticity in functional connectivity following a minimum six-week intervention to train cognitive performance in a speed reading task. Long-term modulation of connectivity with language regions indicate functional connectivity as a candidate biomarker for tracking and measuring functional changes in neural systems as outcomes of cognitive training. The third study demonstrates utility of functional biomarkers in predicting individual differences in behavioral and cognitive features. We successfully predict three major domains of personality psychologyintelligence, agreeableness, and conscientiousnessin individual subjects using a large (N=475) open source data sample compiled by the National Institutes of Healths Human Connectome Project

Dynamic brain networks explored by structure-revealing methods

The human brain is a complex system able to continuously adapt. How and where brain activity is modulated by behavior can be studied with functional magnetic resonance imaging (fMRI), a non-invasive neuroimaging technique with excellent spatial resolution and whole-brain coverage. FMRI scans of healthy adults completing a variety of behavioral tasks have greatly contributed to our understanding of the functional role of individual brain regions. However, by statistically analyzing each region independently, these studies ignore that brain regions act in concert rather than in unison. Thus, many studies since have instead examined how brain regions interact. Surprisingly, structured interactions between distinct brain regions not only occur during behavioral tasks but also while a subject rests quietly in the MRI scanner. Multiple groups of regions interact very strongly with each other and not only do these groups bear a striking resemblance to the sets of regions co-activated in tasks, but many of these interactions are also progressively disrupted in neurological diseases. This suggests that spontaneous fluctuations in activity can provide novel insights into fundamental organizing principles of the human brain in health and disease. Many techniques to date have segregated regions into spatially distinct networks, which ignores that any brain region can take part in multiple networks across time. A more natural view is to estimate dynamic brain networks that allow flexible functional interactions (or connectivity) over time. The estimation and analysis of such dynamic functional interactions is the subject of this dissertation. We take the perspective that dynamic brain networks evolve in a low-dimensional space and can be described by a small number of characteristic spatiotemporal patterns. Our proposed approaches are based on well-established statistical methods, such as principal component analysis (PCA), sparse matrix decompositions, temporal clustering, as well as a multiscale analysis by novel graph wavelet designs. We adapt and extend these methods to the analysis of dynamic brain networks. We show that PCA and its higher-order equivalent can identify co-varying functional interactions, which reveal disturbed dynamic properties in multiple sclerosis and which are related to the timing of stimuli for task studies, respectively. Further we show that sparse matrix decompositions provide a valid alternative approach to PCA and improve interpretability of the identified patterns. Finally, assuming an even simpler low-dimensional space and the exclusive temporal expression of individual patterns, we show that specific transient interactions of the medial prefrontal cortex are disturbed in aging and relate to impaired memory

Functional Connectivity Eigennetworks Reveal Different Brain Dynamics In Multiple Sclerosis Patients

Resting state functional connectivity is defined as correlations in brain activity measured by functional magnetic resonance imaging without any stimulation paradigm. Such connectivity is dynamic, even over the course of minutes, and the development of tools for its analysis is an important challenge in neuroscience. We propose a novel data-driven technique to extract connectivity patterns from dynamic whole-brain networks of multiple subjects. Our technique is based on singular value decomposition and decomposes a collection of networks into linearly independent "eigennetworks" and associated time courses. To deal with the temporal redundancy of networks, we propose a novel subsampling method based on the standard deviation of the connectivity strength. We apply the proposed technique to dynamic resting-state networks of healthy subjects and multiple sclerosis patients, and show its potential to detect aberrant connectivity patterns in patients

This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Tight Wavelet Frames on Multislice Graphs 1

We present a framework for the design of wavelet transforms tailored to data defined on multislice graphs (i.e., multiplex or dynamic graphs). Graphs with multiple types of interactions are ubiquitous in real life, motivating the extension of wavelets to these complex domains. Our framework generalizes the recently proposed spectral graph wavelet transform (SGWT) [1], which is designed in the spectral (frequency) domain of an arbitrary finite weighted graph. We extend the SGWT to form a tight frame, which conserves energy in the wavelet domain, and define the relationship between conventional and spectral graph wavelets. We then propose a design for multislice graphs that is based on the higher-order singular value decomposition (HOSVD), a powerful tool from multilinear algebra. In particular, the multiple adjacency matrices are stacked to form a tensor and the HOSVD decomposition provides information about its third-order structure, analogous to that provided by matrix factorizations. We obtain a set of “eigennetworks ” and from these graph wavelets, which exploit the variability across the graphs. We demonstrate the feasibility of our method (1) by capturing different orientations of a gray-scale image and (2) by decomposing brain signals from functional magnetic resonance imaging. We show its effectiveness to identify variability across graph edges and provide meaningful decompositions. Index Terms Wavelet transform, spectral graph theory, multislice graph, tensor decompositions, higher-order singular value decomposition (HOSVD). Copyright (c) 2012 IEEE. Personal use of this material is permitted. However, permission to use this material for any other purposes must be obtained from the IEEE by sending a request to [email protected]