Optimum Experimental Design Issues in Functional Neuroimaging Studies

abstract: Functional magnetic resonance imaging (fMRI) is one of the popular tools to study human brain functions. High-quality experimental designs are crucial to the success of fMRI experiments as they allow the collection of informative data for making precise and valid inference with minimum cost. The primary goal of this study is on identifying the best sequence of mental stimuli (i.e. fMRI design) with respect to some statistically meaningful optimality criteria. This work focuses on two related topics in this research field. The first topic is on finding optimal designs for fMRI when the design matrix is uncertain. This challenging design issue occurs in many modern fMRI experiments, in which the design matrix of the statistical model depends on both the selected design and the experimental subject's uncertain behavior during the experiment. As a result, the design matrix cannot be fully determined at the design stage that makes it difficult to select a good design. For the commonly used linear model with autoregressive errors, this study proposes a very efficient approach for obtaining high-quality fMRI designs for such experiments. The proposed approach is built upon an analytical result, and an efficient computer algorithm. It is shown through case studies that our proposed approach can outperform the existing method in terms of computing time, and the quality of the obtained designs. The second topic of the research is to find optimal designs for fMRI when a wavelet-based technique is considered in the fMRI data analysis. An efficient computer algorithm to search for optimal fMRI designs for such cases is developed. This algorithm is inspired by simulated annealing and a recently proposed algorithm by Saleh et al. (2017). As demonstrated in the case studies, the proposed approach makes it possible to efficiently obtain high-quality designs for fMRI studies, and is practically useful.Dissertation/ThesisDoctoral Dissertation Applied Mathematics 201

Mapping hybrid functional-structural connectivity traits in the human connectome

One of the crucial questions in neuroscience is how a rich functional repertoire of brain states relates to its underlying structural organization. How to study the associations between these structural and functional layers is an open problem that involves novel conceptual ways of tackling this question. We here propose an extension of the Connectivity Independent Component Analysis (connICA) framework, to identify joint structural-functional connectivity traits. Here, we extend connICA to integrate structural and functional connectomes by merging them into common hybrid connectivity patterns that represent the connectivity fingerprint of a subject. We test this extended approach on the 100 unrelated subjects from the Human Connectome Project. The method is able to extract main independent structural-functional connectivity patterns from the entire cohort that are sensitive to the realization of different tasks. The hybrid connICA extracted two main task-sensitive hybrid traits. The first, encompassing the within and between connections of dorsal attentional and visual areas, as well as fronto-parietal circuits. The second, mainly encompassing the connectivity between visual, attentional, DMN and subcortical networks. Overall, these findings confirms the potential ofthe hybrid connICA for the compression of structural/functional connectomes into integrated patterns from a set of individual brain networks.Comment: article: 34 pages, 4 figures; supplementary material: 5 pages, 5 figure

One-Class Classification: Taxonomy of Study and Review of Techniques

One-class classification (OCC) algorithms aim to build classification models when the negative class is either absent, poorly sampled or not well defined. This unique situation constrains the learning of efficient classifiers by defining class boundary just with the knowledge of positive class. The OCC problem has been considered and applied under many research themes, such as outlier/novelty detection and concept learning. In this paper we present a unified view of the general problem of OCC by presenting a taxonomy of study for OCC problems, which is based on the availability of training data, algorithms used and the application domains applied. We further delve into each of the categories of the proposed taxonomy and present a comprehensive literature review of the OCC algorithms, techniques and methodologies with a focus on their significance, limitations and applications. We conclude our paper by discussing some open research problems in the field of OCC and present our vision for future research.Comment: 24 pages + 11 pages of references, 8 figure

Maximin Designs for Event-Related fMRI with Uncertain Error Correlation

abstract: One of the premier technologies for studying human brain functions is the event-related functional magnetic resonance imaging (fMRI). The main design issue for such experiments is to find the optimal sequence for mental stimuli. This optimal design sequence allows for collecting informative data to make precise statistical inferences about the inner workings of the brain. Unfortunately, this is not an easy task, especially when the error correlation of the response is unknown at the design stage. In the literature, the maximin approach was proposed to tackle this problem. However, this is an expensive and time-consuming method, especially when the correlated noise follows high-order autoregressive models. The main focus of this dissertation is to develop an efficient approach to reduce the amount of the computational resources needed to obtain A-optimal designs for event-related fMRI experiments. One proposed idea is to combine the Kriging approximation method, which is widely used in spatial statistics and computer experiments with a knowledge-based genetic algorithm. Through case studies, a demonstration is made to show that the new search method achieves similar design efficiencies as those attained by the traditional method, but the new method gives a significant reduction in computing time. Another useful strategy is also proposed to find such designs by considering only the boundary points of the parameter space of the correlation parameters. The usefulness of this strategy is also demonstrated via case studies. The first part of this dissertation focuses on finding optimal event-related designs for fMRI with simple trials when each stimulus consists of only one component (e.g., a picture). The study is then extended to the case of compound trials when stimuli of multiple components (e.g., a cue followed by a picture) are considered.Dissertation/ThesisDoctoral Dissertation Statistics 201

Stability and Application of the k-core Dynamical Model to Biological Networks

The objective of the dissertation is to illustrate the importance of the k-core dynamical model, by first presenting the stability analysis of the nonlinear k-core model and compare its solution to the most widely used linear model. Second, I show a real world application of the k-core model to describe properties of neural networks, specifically, the transition from conscious to subliminal perception

Optimal Design of Experiments for Functional Responses

abstract: Functional or dynamic responses are prevalent in experiments in the fields of engineering, medicine, and the sciences, but proposals for optimal designs are still sparse for this type of response. Experiments with dynamic responses result in multiple responses taken over a spectrum variable, so the design matrix for a dynamic response have more complicated structures. In the literature, the optimal design problem for some functional responses has been solved using genetic algorithm (GA) and approximate design methods. The goal of this dissertation is to develop fast computer algorithms for calculating exact D-optimal designs. First, we demonstrated how the traditional exchange methods could be improved to generate a computationally efficient algorithm for finding G-optimal designs. The proposed two-stage algorithm, which is called the cCEA, uses a clustering-based approach to restrict the set of possible candidates for PEA, and then improves the G-efficiency using CEA. The second major contribution of this dissertation is the development of fast algorithms for constructing D-optimal designs that determine the optimal sequence of stimuli in fMRI studies. The update formula for the determinant of the information matrix was improved by exploiting the sparseness of the information matrix, leading to faster computation times. The proposed algorithm outperforms genetic algorithm with respect to computational efficiency and D-efficiency. The third contribution is a study of optimal experimental designs for more general functional response models. First, the B-spline system is proposed to be used as the non-parametric smoother of response function and an algorithm is developed to determine D-optimal sampling points of a spectrum variable. Second, we proposed a two-step algorithm for finding the optimal design for both sampling points and experimental settings. In the first step, the matrix of experimental settings is held fixed while the algorithm optimizes the determinant of the information matrix for a mixed effects model to find the optimal sampling times. In the second step, the optimal sampling times obtained from the first step is held fixed while the algorithm iterates on the information matrix to find the optimal experimental settings. The designs constructed by this approach yield superior performance over other designs found in literature.Dissertation/ThesisDoctoral Dissertation Industrial Engineering 201