Hyper-connectivity of functional networks for brain disease diagnosis

Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer’s disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also help discover disease-related biomarkers important for disease diagnosis

Ensemble Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Complex Graph Measures from Diffusion Tensor Images

The human brain is a complex network of interacting regions. The gray matter regions of brain are interconnected by white matter tracts, together forming one integrative complex network. In this article, we report our investigation about the potential of applying brain connectivity patterns as an aid in diagnosing Alzheimer's disease and Mild Cognitive Impairment (MCI). We performed pattern analysis of graph theoretical measures derived from Diffusion Tensor Imaging (DTI) data representing structural brain networks of 45 subjects, consisting of 15 patients of Alzheimer's disease (AD), 15 patients of MCI, and 15 healthy subjects (CT). We considered pair-wise class combinations of subjects, defining three separate classification tasks, i.e., AD-CT, AD-MCI, and CT-MCI, and used an ensemble classification module to perform the classification tasks. Our ensemble framework with feature selection shows a promising performance with classification accuracy of 83.3% for AD vs. MCI, 80% for AD vs. CT, and 70% for MCI vs. CT. Moreover, our findings suggest that AD can be related to graph measures abnormalities at Brodmann areas in the sensorimotor cortex and piriform cortex. In this way, node redundancy coefficient and load centrality in the primary motor cortex were recognized as good indicators of AD in contrast to MCI. In general, load centrality, betweenness centrality, and closeness centrality were found to be the most relevant network measures, as they were the top identified features at different nodes. The present study can be regarded as a “proof of concept” about a procedure for the classification of MRI markers between AD dementia, MCI, and normal old individuals, due to the small and not well-defined groups of AD and MCI patients. Future studies with larger samples of subjects and more sophisticated patient exclusion criteria are necessary toward the development of a more precise technique for clinical diagnosis

Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer\u27s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, \u27shape connections\u27 between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus