Identifying the neuroanatomical basis of cognitive impairment in Alzheimer's disease by correlation- and nonlinearity-aware sparse Bayesian learning

Predicting cognitive performance of subjects from their magnetic resonance imaging (MRI) measures and identifying relevant imaging biomarkers are important research topics in the study of Alzheimer's disease. Traditionally, this task is performed by formulating a linear regression problem. Recently, it is found that using a linear sparse regression model can achieve better prediction accuracy. However, most existing studies only focus on the exploitation of sparsity of regression coefficients, ignoring useful structure information in regression coefficients. Also, these linear sparse models may not capture more complicated and possibly nonlinear relationships between cognitive performance and MRI measures. Motivated by these observations, in this work we build a sparse multivariate regression model for this task and propose an empirical sparse Bayesian learning algorithm. Different from existing sparse algorithms, the proposed algorithm models the response as a nonlinear function of the predictors by extending the predictor matrix with block structures. Further, it exploits not only inter-vector correlation among regression coefficient vectors, but also intra-block correlation in each regression coefficient vector. Experiments on the Alzheimer's Disease Neuroimaging Initiative database showed that the proposed algorithm not only achieved better prediction performance than state-of-the-art competitive methods, but also effectively identified biologically meaningful patterns

Temporally Constrained Group Sparse Learning for Longitudinal Data Analysis in Alzheimer's Disease

Sparse learning has been widely investigated for analysis of brain images to assist the diagnosis of Alzheimer’s disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). However, most existing sparse learning-based studies only adopt cross-sectional analysis methods, where the sparse model is learned using data from a single time-point. Actually, multiple time-points of data are often available in brain imaging applications, which can be used in some longitudinal analysis methods to better uncover the disease progression patterns. Accordingly, in this paper we propose a novel temporally-constrained group sparse learning method aiming for longitudinal analysis with multiple time-points of data. Specifically, we learn a sparse linear regression model by using the imaging data from multiple time-points, where a group regularization term is first employed to group the weights for the same brain region across different time-points together. Furthermore, to reflect the smooth changes between data derived from adjacent time-points, we incorporate two smoothness regularization terms into the objective function, i.e., one fused smoothness term which requires that the differences between two successive weight vectors from adjacent time-points should be small, and another output smoothness term which requires the differences between outputs of two successive models from adjacent time-points should also be small. We develop an efficient optimization algorithm to solve the proposed objective function. Experimental results on ADNI database demonstrate that, compared with conventional sparse learning-based methods, our proposed method can achieve improved regression performance and also help in discovering disease-related biomarkers

Progression Modeling of Cognitive Disease Using Temporal Data Mining: Research Landscape, Gaps and Solution Design

Dementia is a cognitive disorder whose diagnosis and progression monitoring is very difficult due to a very slow onset and progression. It is difficult to detect whether cognitive decline is due to ageing process or due to some form of dementia as MRI scans of the brain cannot reliably differentiate between ageing related volume loss and pathological changes. Laboratory tests on blood or CSF samples have also not proved very useful. Alzheimer�s disease (AD) is recognized as the most common cause of dementia. Development of sensitive and reliable tool for evaluation in terms of early diagnosis and progression monitoring of AD is required. Since there is an absence of specific markers for predicting AD progression, there is a need to learn more about specific attributes and their temporal relationships that lead to this disease and determine progression from mild cognitive impairment to full blown AD. Various stages of disease and transitions from one stage to the have be modelled based on longitudinal patient data. This paper provides a critical review of the methods to understand disease progression modelling and determine factors leading to progression of AD from initial to final stages. Then the design of a machine learning based solution is proposed to handle the gaps in current research

Network-guided sparse learning for predicting cognitive outcomes from MRI measures

Alzheimer's disease (AD) is characterized by gradual neurodegeneration and loss of brain function, especially for memory during early stages. Regression analysis has been widely applied to AD research to relate clinical and biomarker data such as predicting cognitive outcomes from MRI measures. In particular, sparse models have been proposed to identify the optimal imaging markers with high prediction power. However, the complex relationship among imaging markers are often overlooked or simplified in the existing methods. To address this issue, we present a new sparse learning method by introducing a novel network term to more flexibly model the relationship among imaging markers. The proposed algorithm is applied to the ADNI study for predicting cognitive outcomes using MRI scans. The effectiveness of our method is demonstrated by its improved prediction performance over several state-of-the-art competing methods and accurate identification of cognition-relevant imaging markers that are biologically meaningful

Learning Discriminative Bayesian Networks from High-dimensional Continuous Neuroimaging Data

Due to its causal semantics, Bayesian networks (BN) have been widely employed to discover the underlying data relationship in exploratory studies, such as brain research. Despite its success in modeling the probability distribution of variables, BN is naturally a generative model, which is not necessarily discriminative. This may cause the ignorance of subtle but critical network changes that are of investigation values across populations. In this paper, we propose to improve the discriminative power of BN models for continuous variables from two different perspectives. This brings two general discriminative learning frameworks for Gaussian Bayesian networks (GBN). In the first framework, we employ Fisher kernel to bridge the generative models of GBN and the discriminative classifiers of SVMs, and convert the GBN parameter learning to Fisher kernel learning via minimizing a generalization error bound of SVMs. In the second framework, we employ the max-margin criterion and build it directly upon GBN models to explicitly optimize the classification performance of the GBNs. The advantages and disadvantages of the two frameworks are discussed and experimentally compared. Both of them demonstrate strong power in learning discriminative parameters of GBNs for neuroimaging based brain network analysis, as well as maintaining reasonable representation capacity. The contributions of this paper also include a new Directed Acyclic Graph (DAG) constraint with theoretical guarantee to ensure the graph validity of GBN.Comment: 16 pages and 5 figures for the article (excluding appendix

Neuroimaging Feature Extraction using a Neural Network Classifier for Imaging Genetics

A major issue in the association of genes to neuroimaging phenotypes is the high dimension of both genetic data and neuroimaging data. In this article, we tackle the latter problem with an eye toward developing solutions that are relevant for disease prediction. Supported by a vast literature on the predictive power of neural networks, our proposed solution uses neural networks to extract from neuroimaging data features that are relevant for predicting Alzheimer's Disease (AD) for subsequent relation to genetics. Our neuroimaging-genetic pipeline is comprised of image processing, neuroimaging feature extraction and genetic association steps. We propose a neural network classifier for extracting neuroimaging features that are related with disease and a multivariate Bayesian group sparse regression model for genetic association. We compare the predictive power of these features to expert selected features and take a closer look at the SNPs identified with the new neuroimaging features.Comment: Under revie