Alterations of dynamic redundancy of functional brain subnetworks in Alzheimer's disease and major depression disorders.

The human brain is not only efficiently but also "redundantly" connected. The redundancy design could help the brain maintain resilience to disease attacks. This paper explores subnetwork-level redundancy dynamics and the potential of such metrics in disease studies. As such, we looked into specific functional subnetworks, including those associated with high-level functions. We investigated how the subnetwork redundancy dynamics change along with Alzheimer's disease (AD) progression and with major depressive disorder (MDD), two major disorders that could share similar subnetwork alterations. We found an increased dynamic redundancy of the subcortical-cerebellum subnetwork and its connections to other high-order subnetworks in the mild cognitive impairment (MCI) and AD compared to the normal control (NC). With gained spatial specificity, we found such a redundancy index was sensitive to disease symptoms and could act as a protective mechanism to prevent the collapse of the brain network and functions. The dynamic redundancy of the medial frontal subnetwork and its connections to the frontoparietal subnetwork was also found decreased in MDD compared to NC. The spatial specificity of the redundancy dynamics changes may provide essential knowledge for a better understanding of shared neural substrates in AD and MDD.

A Computational Framework for Dissociating Development-Related from Individually Variable Flexibility in Regional Modularity Assignment in Early Infancy.

Functional brain development in early infancy is a highly dynamic and complex process. Understanding each brain region's topological role and its development in the brain functional connectivity (FC) networks is essential for early disorder detection. A handful of previous studies have mostly focused on how FC network is changing regarding age. These approaches inevitably overlook the effect of individual variability for those at the same age that could shape unique cognitive capabilities and personalities among infants. With that in mind, we propose a novel computational framework based on across-subject across-age multilayer network analysis with a fully automatic (for parameter optimization), robust community detection algorithm. By detecting group consistent modules without losing individual information, this method allows a first-ever dissociation analysis of the two variability sources - age dependency and individual specificity - that greatly shape early brain development. This method is applied to a large cohort of 0-2 years old infants' functional MRI data during natural sleep. We not only detected the brain regions with greatest flexibility in this early developmental period but also identified five categories of brain regions with distinct development-related and individually variable flexibility changes. Our method is highly valuable for more thorough understanding of the early brain functional organizations and sheds light on early developmental abnormality detection.

Unsupervised Manifold Learning Using High-Order Morphological Brain Networks Derived From T1-w MRI for Autism Diagnosis.

Brain disorders, such as Autism Spectrum Disorder (ASD), alter brain functional (from fMRI) and structural (from diffusion MRI) connectivities at multiple levels and in varying degrees. While unraveling such alterations have been the focus of a large number of studies, morphological brain connectivity has been out of the research scope. In particular, shape-to-shape relationships across brain regions of interest (ROIs) were rarely investigated. As such, the use of networks based on morphological brain data in neurological disorder diagnosis, while leveraging the advent of machine learning, could complement our knowledge on brain wiring alterations in unprecedented ways. In this paper, we use conventional T1-weighted MRI to define morphological brain networks (MBNs), each quantifying shape relationship between different cortical regions for a specific cortical attribute at both low-order and high-order levels. While typical brain connectomes investigate the relationship between two ROIs, we propose high-order MBN which better captures brain complex interactions by modeling the morphological relationship between pairs of ROIs. For ASD identification, we present a connectomic manifold learning framework, which learns multiple kernels to estimate a similarity measure between ASD and normal controls (NC) connectional features, to perform dimensionality reduction for clustering ASD and NC subjects. We benchmark our ASD identification method against both supervised and unsupervised state-of-the-art methods, while depicting the most discriminative high- and low-order relationships between morphological regions in the left and right hemispheres.