A Novel Joint Brain Network Analysis Using Longitudinal Alzheimer's Disease Data.

There is well-documented evidence of brain network differences between individuals with Alzheimer's disease (AD) and healthy controls (HC). To date, imaging studies investigating brain networks in these populations have typically been cross-sectional, and the reproducibility of such findings is somewhat unclear. In a novel study, we use the longitudinal ADNI data on the whole brain to jointly compute the brain network at baseline and one-year using a state of the art approach that pools information across both time points to yield distinct visit-specific networks for the AD and HC cohorts, resulting in more accurate inferences. We perform a multiscale comparison of the AD and HC networks in terms of global network metrics as well as at the more granular level of resting state networks defined under a whole brain parcellation. Our analysis illustrates a decrease in small-worldedness in the AD group at both the time points and also identifies more local network features and hub nodes that are disrupted due to the progression of AD. We also obtain high reproducibility of the HC network across visits. On the other hand, a separate estimation of the networks at each visit using standard graphical approaches reveals fewer meaningful differences and lower reproducibility

Topological properties of modular networks, with a focus on networks of functional connections in the human brain

Complex network theory offers useful approaches to analyze the structural and functional properties of real life networks. In this work, we explore some of the mathematical concepts of network theory and study real life systems from a complex network perspective. We pay particular attention to networks of connections within the human brain. We analyze weighted networks calculated from full functional magnetic resonance imaging (fMRI) data acquired during task performance. The first novelty of this study is the fact that we retain all of the connections between all of the voxels in the full brain fMRI data. We then evaluate the extent to which this rich dataset can be described by existing models of scale-free or exponentially truncated scale-free topology, comparing results across a large number of more complex topological models as well. Our results suggest that the novel model presented in this dissertation offers a significantly better fit at the voxel level. Structural characterization of the brain can also give insights into the effects of traumatic injuries. For our second study, we used brain networks to explore the topological consequences of brain damage in computational models. By simulating the effects of several traumatic brain injury (TBI) models we find a variety of disruptions in the modular structure and connectivity of the post-injury networks. In particular, we focused on the effects of focalized injuries, axonal degeneration and diffuse microlesions. Our results suggest that mathematical models can predict, to some extent, the structural and functional effects of TBIs based on the analysis of specific topological measures. Furthermore, these results may be correlated to known cognitive sequelae of TBI. In order to complement the set of topological properties studied, we review the concept of participation of a node in a modular network. The participation coefficient is often used to provide a ranking of the importance of a node; however, we propose a new measure, called the gateway coefficient, to assess the involvement of a node. Our results suggest that the gateway coefficient has a superior ranking power than the participation coefficient since it takes into account a variety of modular properties of the network. These results are illustrated with examples of simulations and real life datasets, such as the air transportation network and the human brain network

The Non-Random Brain: Efficiency, Economy, and Complex Dynamics

Modern anatomical tracing and imaging techniques are beginning to reveal the structural anatomy of neural circuits at small and large scales in unprecedented detail. When examined with analytic tools from graph theory and network science, neural connectivity exhibits highly non-random features, including high clustering and short path length, as well as modules and highly central hub nodes. These characteristic topological features of neural connections shape non-random dynamic interactions that occur during spontaneous activity or in response to external stimulation. Disturbances of connectivity and thus of neural dynamics are thought to underlie a number of disease states of the brain, and some evidence suggests that degraded functional performance of brain networks may be the outcome of a process of randomization affecting their nodes and edges. This article provides a survey of the non-random structure of neural connectivity, primarily at the large scale of regions and pathways in the mammalian cerebral cortex. In addition, we will discuss how non-random connections can give rise to differentiated and complex patterns of dynamics and information flow. Finally, we will explore the idea that at least some disorders of the nervous system are associated with increased randomness of neural connections

Loss of brain inter-frequency hubs in Alzheimer's disease

Alzheimer's disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD subjects was abnormally distributed across frequency bands as compared to controls, causing significant decreases of MPC. This effect was mainly localized in association areas and in the cingulate cortex, which acted, in the healthy group, as a true inter-frequency hub. MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-beta deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings shed new light on the brain functional alterations underlying AD and provide analytical tools for identifying multi-frequency neural mechanisms of brain diseases.Comment: 27 pages, 6 figures, 3 tables, 3 supplementary figure

Estimating Time-Varying Effective Connectivity in High-Dimensional fMRI Data Using Regime-Switching Factor Models

Recent studies on analyzing dynamic brain connectivity rely on sliding-window analysis or time-varying coefficient models which are unable to capture both smooth and abrupt changes simultaneously. Emerging evidence suggests state-related changes in brain connectivity where dependence structure alternates between a finite number of latent states or regimes. Another challenge is inference of full-brain networks with large number of nodes. We employ a Markov-switching dynamic factor model in which the state-driven time-varying connectivity regimes of high-dimensional fMRI data are characterized by lower-dimensional common latent factors, following a regime-switching process. It enables a reliable, data-adaptive estimation of change-points of connectivity regimes and the massive dependencies associated with each regime. We consider the switching VAR to quantity the dynamic effective connectivity. We propose a three-step estimation procedure: (1) extracting the factors using principal component analysis (PCA) and (2) identifying dynamic connectivity states using the factor-based switching vector autoregressive (VAR) models in a state-space formulation using Kalman filter and expectation-maximization (EM) algorithm, and (3) constructing the high-dimensional connectivity metrics for each state based on subspace estimates. Simulation results show that our proposed estimator outperforms the K-means clustering of time-windowed coefficients, providing more accurate estimation of regime dynamics and connectivity metrics in high-dimensional settings. Applications to analyzing resting-state fMRI data identify dynamic changes in brain states during rest, and reveal distinct directed connectivity patterns and modular organization in resting-state networks across different states.Comment: 21 page

Intrinsic Architecture Underlying the Relations among the Default, Dorsal Attention, and Frontoparietal Control Networks of the Human Brain

Human cognition is increasingly characterized as an emergent property of interactions among distributed, functionally specialized brain networks. We recently demonstrated that the antagonistic “default” and “dorsal attention” networks—subserving internally and externally directed cognition, respectively—are modulated by a third “frontoparietal control” network that flexibly couples with either network depending on task domain. However, little is known about the intrinsic functional architecture underlying this relationship. We used graph theory to analyze network properties of intrinsic functional connectivity within and between these three large-scale networks. Task-based activation from three independent studies were used to identify reliable brain regions (“nodes”) of each network. We then examined pairwise connections (“edges”) between nodes, as defined by resting-state functional connectivity MRI. Importantly, we used a novel bootstrap resampling procedure to determine the reliability of graph edges. Furthermore, we examined both full and partial correlations. As predicted, there was a higher degree of integration within each network than between networks. Critically, whereas the default and dorsal attention networks shared little positive connectivity with one another, the frontoparietal control network showed a high degree of between-network interconnectivity with each of these networks. Furthermore, we identified nodes within the frontoparietal control network of three different types—default-aligned, dorsal attention-aligned, and dual-aligned—that we propose play dissociable roles in mediating internetwork communication. The results provide evidence consistent with the idea that the frontoparietal control network plays a pivotal gate-keeping role in goal-directed cognition, mediating the dynamic balance between default and dorsal attention networks.Psycholog

Enhanced pre-frontal functional-structural networks to support postural control deficits after traumatic brain injury in a pediatric population

Traumatic brain injury (TBI) affects the structural connectivity, triggering the re-organization of structural-functional circuits in a manner that remains poorly understood. We focus here on brain networks re-organization in relation to postural control deficits after TBI. We enrolled young participants who had suffered moderate to severeTBI, comparing them to young typically developing control participants. In comparison to control participants, TBI patients (but not controls) recruited prefrontal regions to interact with two separated networks: 1) a subcortical network including part of the motor network, basal ganglia, cerebellum, hippocampus, amygdala, posterior cingulum and precuneus; and 2) a task-positive network, involving regions of the dorsal attention system together with the dorsolateral and ventrolateral prefrontal regions