Neuroimaging feature extraction using a neural network classifier for imaging genetics.

BACKGROUND: Dealing with the high dimension of both neuroimaging data and genetic data is a difficult problem in the association of genetic data to neuroimaging. 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. The neuroimaging-genetic pipeline we propose is comprised of image processing, neuroimaging feature extraction and genetic association steps. We present a neural network classifier for extracting neuroimaging features that are related with the disease. The proposed method is data-driven and requires no expert advice or a priori selection of regions of interest. We further propose a multivariate regression with priors specified in the Bayesian framework that allows for group sparsity at multiple levels including SNPs and genes. RESULTS: We find the features extracted with our proposed method are better predictors of AD than features used previously in the literature suggesting that single nucleotide polymorphisms (SNPs) related to the features extracted by our proposed method are also more relevant for AD. Our neuroimaging-genetic pipeline lead to the identification of some overlapping and more importantly some different SNPs when compared to those identified with previously used features. CONCLUSIONS: The pipeline we propose combines machine learning and statistical methods to benefit from the strong predictive performance of blackbox models to extract relevant features while preserving the interpretation provided by Bayesian models for genetic association. Finally, we argue in favour of using automatic feature extraction, such as the method we propose, in addition to ROI or voxelwise analysis to find potentially novel disease-relevant SNPs that may not be detected when using ROIs or voxels alone.

Functional Connectivity Methods and Their Applications in fMRI Data.

The availability of powerful non-invasive neuroimaging techniques has given rise to various studies that aim to map the human brain. These studies focus on not only finding brain activation signatures but also on understanding the overall organization of functional communication in the brain network. Based on the principle that distinct brain regions are functionally connected and continuously share information with each other, various approaches to finding these functional networks have been proposed in the literature. In this paper, we present an overview of the most common methods to estimate and characterize functional connectivity in fMRI data. We illustrate these methodologies with resting-state functional MRI data from the Human Connectome Project, providing details of their implementation and insights on the interpretations of the results. We aim to guide researchers that are new to the field of neuroimaging by providing the necessary tools to estimate and characterize brain circuitry.

A Review of Bayesian Hypothesis Testing and Its Practical Implementations.

We discuss hypothesis testing and compare different theories in light of observed or experimental data as fundamental endeavors in the sciences. Issues associated with the p-value approach and null hypothesis significance testing are reviewed, and the Bayesian alternative based on the Bayes factor is introduced, along with a review of computational methods and sensitivity related to prior distributions. We demonstrate how Bayesian testing can be practically implemented in several examples, such as the t-test, two-sample comparisons, linear mixed models, and Poisson mixed models by using existing software. Caveats and potential problems associated with Bayesian testing are also discussed. We aim to inform researchers in the many fields where Bayesian testing is not in common use of a well-developed alternative to null hypothesis significance testing and to demonstrate its standard implementation.

Predicting Upcoming Events Occurring in the Space Surrounding the Hand.

Predicting upcoming sensorimotor events means creating forward estimates of the body and the surrounding world. This ability is a fundamental aspect of skilled motor behavior and requires an accurate and constantly updated representation of the body and the environment. To test whether these prediction mechanisms could be affected by a peripheral injury, we employed an action observation and electroencephalogram (EEG) paradigm to assess the occurrence of prediction markers in anticipation of observed sensorimotor events in healthy and brachial plexus injury (BPI) participants. Nine healthy subjects and six BPI patients watched a series of video clips showing an actor's hand and a colored ball in an egocentric perspective. The color of the ball indicated whether the hand would grasp it (hand movement), or the ball would roll toward the hand and touch it (ball movement), or no event would occur (no movement). In healthy participants, we expected to find distinct electroencephalographic activation patterns (EEG signatures) specific to the prediction of the occurrence of each of these situations. Cluster analysis from EEG signals recorded from electrodes placed over the sensorimotor cortex of control participants showed that predicting either an upcoming hand movement or the occurrence of a tactile event yielded specific neural signatures. In BPI participants, the EEG signals from the sensorimotor cortex contralateral to the dominant hand in the hand movement condition were different compared to the other conditions. Furthermore, there were no differences between ball movement and no movement conditions in the sensorimotor cortex contralateral to the dominant hand, suggesting that BPI blurred specifically the ability to predict upcoming tactile events for the dominant hand. These results highlight the role of the sensorimotor cortex in creating estimates of both actions and tactile interactions in the space around the body and suggest plastic effects on prediction coding following peripheral sensorimotor loss.

Bayesian Semiparametric Functional Mixed Models for Serially Correlated Functional Data, with Application to Glaucoma Data.

Glaucoma, a leading cause of blindness, is characterized by optic nerve damage related to intraocular pressure (IOP), but its full etiology is unknown. Researchers at UAB have devised a custom device to measure scleral strain continuously around the eye under fixed levels of IOP, which here is used to assess how strain varies around the posterior pole, with IOP, and across glaucoma risk factors such as age. The hypothesis is that scleral strain decreases with age, which could alter biomechanics of the optic nerve head and cause damage that could eventually lead to glaucoma. To evaluate this hypothesis, we adapted Bayesian Functional Mixed Models to model these complex data consisting of correlated functions on spherical scleral surface, with nonparametric age effects allowed to vary in magnitude and smoothness across the scleral surface, multi-level random effect functions to capture within-subject correlation, and functional growth curve terms to capture serial correlation across IOPs that can vary around the scleral surface. Our method yields fully Bayesian inference on the scleral surface or any aggregation or transformation thereof, and reveals interesting insights into the biomechanical etiology of glaucoma. The general modeling framework described is very flexible and applicable to many complex, high-dimensional functional data.

TPRM: TENSOR PARTITION REGRESSION MODELS WITH APPLICATIONS IN IMAGING BIOMARKER DETECTION.

Medical imaging studies have collected high dimensional imaging data to identify imaging biomarkers for diagnosis, screening, and prognosis, among many others. These imaging data are often represented in the form of a multi-dimensional array, called a tensor. The aim of this paper is to develop a tensor partition regression modeling (TPRM) framework to establish a relationship between low-dimensional clinical outcomes (e.g., diagnosis) and high dimensional tensor covariates. Our TPRM is a hierarchical model and efficiently integrates four components: (i) a partition model, (ii) a canonical polyadic decomposition model, (iii) a principal components model, and (iv) a generalized linear model with a sparse inducing normal mixture prior. This framework not only reduces ultra-high dimensionality to a manageable level, resulting in efficient estimation, but also optimizes prediction accuracy in the search for informative subtensors. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. Simulation shows that TPRM outperforms several other competing methods. We apply TPRM to predict disease status (Alzheimer versus control) by using structural magnetic resonance imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

Bayesian spatial transformation models with applications in neuroimaging data.

The aim of this article is to develop a class of spatial transformation models (STM) to spatially model the varying association between imaging measures in a three-dimensional (3D) volume (or 2D surface) and a set of covariates. The proposed STM include a varying Box-Cox transformation model for dealing with the issue of non-Gaussian distributed imaging data and a Gaussian Markov random field model for incorporating spatial smoothness of the imaging data. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. Simulations and real data analysis demonstrate that the STM significantly outperforms the voxel-wise linear model with Gaussian noise in recovering meaningful geometric patterns. Our STM is able to reveal important brain regions with morphological changes in children with attention deficit hyperactivity disorder.