Connectome-scale assessments of structural and functional connectivity in MCI.

Mild cognitive impairment (MCI) has received increasing attention not only because of its potential as a precursor for Alzheimer's disease but also as a predictor of conversion to other neurodegenerative diseases. Although MCI has been defined clinically, accurate and efficient diagnosis is still challenging. Although neuroimaging techniques hold promise, compared to commonly used biomarkers including amyloid plaques, tau protein levels and brain tissue atrophy, neuroimaging biomarkers are less well validated. In this article, we propose a connectomes-scale assessment of structural and functional connectivity in MCI via two independent multimodal DTI/fMRI datasets. We first used DTI-derived structural profiles to explore and tailor the most common and consistent landmarks, then applied them in a whole-brain functional connectivity analysis. The next step fused the results from two independent datasets together and resulted in a set of functional connectomes with the most differentiation power, hence named as "connectome signatures." Our results indicate that these "connectome signatures" have significantly high MCI-vs-controls classification accuracy, at more than 95%. Interestingly, through functional meta-analysis, we found that the majority of "connectome signatures" are mainly derived from the interactions among different functional networks, for example, cognition-perception and cognition-action domains, rather than from within a single network. Our work provides support for using functional "connectome signatures" as neuroimaging biomarkers of MCI.

Atomic connectomics signatures for characterization and differentiation of mild cognitive impairment.

In recent years, functional connectomics signatures have been shown to be a very valuable tool in characterizing and differentiating brain disorders from normal controls. However, if the functional connectivity alterations in a brain disease are localized within sub-networks of a connectome, then accurate identification of such disease-specific sub-networks is critical and this capability entails both fine-granularity definition of connectome nodes and effective clustering of connectome nodes into disease-specific and non-disease-specific sub-networks. In this work, we adopted the recently developed DICCCOL (dense individualized and common connectivity-based cortical landmarks) system as a fine-granularity high-resolution connectome construction method to deal with the first issue, and employed an effective variant of non-negative matrix factorization (NMF) method to pinpoint disease-specific sub-networks, which we called atomic connectomics signatures in this work. We have implemented and applied this novel framework to two mild cognitive impairment (MCI) datasets from two different research centers, and our experimental results demonstrated that the derived atomic connectomics signatures can effectively characterize and differentiate MCI patients from their normal controls. In general, our work contributed a novel computational framework for deriving descriptive and distinctive atomic connectomics signatures in brain disorders.