Decoding Task-Based fMRI Data Using Graph Neural Networks, Considering Individual Differences

Functional magnetic resonance imaging (fMRI) is a non-invasive technology that provides high spatial resolution in determining the human brain\u27s responses and measures regional brain activity through metabolic changes in blood oxygen consumption associated with neural activity. Task fMRI provides an opportunity to analyze the working mechanisms of the human brain during specific task performance. Over the past several years, a variety of computational methods have been proposed to decode task fMRI data that can identify brain regions associated with different task stimulations. Despite the advances made by these methods, several limitations exist due to graph representations and graph embeddings transferred from task fMRI signals. In the present study, we proposed an end-to-end graph convolutional network by combining the convolutional neural network with graph representation, with three convolutional layers to classify task fMRI data from the Human Connectome Project (302 participants, 22–35 years of age). One goal of this dissertation was to improve classification performance. We applied four of the most widely used node embedding algorithms—NetMF, RandNE, Node2Vec, and Walklets—to automatically extract the structural properties of the nodes in the brain functional graph, then evaluated the performance of the classification model. The empirical results indicated that the proposed GCN framework accurately identified the brain\u27s state in task fMRI data and achieved comparable macro F1 scores of 0.978 and 0.976 with the NetMF and RandNE embedding methods, respectively. Another goal of the dissertation was to assess the effects of individual differences (i.e., gender and fluid intelligence) on classification performance. We tested the proposed GCN framework on sub-datasets divided according to gender and fluid intelligence. Experimental results indicated significant differences in the classification predictions of gender, but not high/low fluid intelligence fMRI data. Our experiments yielded promising results and demonstrated the superior ability of our GCN in modeling task fMRI data

Application of Deep Learning to Brain Connectivity Classification in Large MRI Datasets

The use of machine learning for whole-brain classification of magnetic resonance imaging (MRI) data is of clear interest, both for understanding phenotypic differences in brain structure and function and for diagnostic applications. Developments of deep learning models in the past decade have revolutionized photographic image and speech recognition, bringing promise to do the same to other fields of science. However, there are many practical and theoretical challenges in the translation of such methods to the unique context of MRIs of the brain. This thesis presents a theoretical underpinning for whole-brain classification of extremely large datasets of multi-site MRIs, including machine learning model architecture, dataset curation methods, machine learning visualization methods, encoding of MRI data, and feature extraction. To replicate large sample sizes typically applied to deep learning models, a dataset of over 50,000 functional and structural MRIs was amassed from nine different databases, and the undertaken analyses were conducted on three covariates commonly found across these collections: sex, resting state/task, and autism spectrum disorder. I find that deep learning is not only a method that has promise for clinical application in the future, but also a powerful statistical tool for analyzing complex, nonlinear relationships in brain data where conventional statistics may fail. However, results are also dependent on factors such as dataset imbalances, confounding factors such as motion and head size, selected methods of encoding MRI data, variability of machine learning models and selected methods of visualizing the machine learning results. In this thesis, I present the following methodological innovations: (1) a method of balancing datasets as a means of regressing out measurable confounding factors; (2) a means of removing spatial biases from deep learning visualization methods; (3) methods of encoding functional and structural datasets as connectivity matrices; (4) the use of ensemble models and convolutional neural network architectures to improve classification accuracy and consistency; (5) adaptation of deep learning visualization methods to study brain connections utilized in the classification process. Additionally, I discuss interpretations, limitations, and future directions of this research.Gates Cambridge Scholarshi

Whole Brain Network Dynamics of Epileptic Seizures at Single Cell Resolution

Epileptic seizures are characterised by abnormal brain dynamics at multiple scales, engaging single neurons, neuronal ensembles and coarse brain regions. Key to understanding the cause of such emergent population dynamics, is capturing the collective behaviour of neuronal activity at multiple brain scales. In this thesis I make use of the larval zebrafish to capture single cell neuronal activity across the whole brain during epileptic seizures. Firstly, I make use of statistical physics methods to quantify the collective behaviour of single neuron dynamics during epileptic seizures. Here, I demonstrate a population mechanism through which single neuron dynamics organise into seizures: brain dynamics deviate from a phase transition. Secondly, I make use of single neuron network models to identify the synaptic mechanisms that actually cause this shift to occur. Here, I show that the density of neuronal connections in the network is key for driving generalised seizure dynamics. Interestingly, such changes also disrupt network response properties and flexible dynamics in brain networks, thus linking microscale neuronal changes with emergent brain dysfunction during seizures. Thirdly, I make use of non-linear causal inference methods to study the nature of the underlying neuronal interactions that enable seizures to occur. Here I show that seizures are driven by high synchrony but also by highly non-linear interactions between neurons. Interestingly, these non-linear signatures are filtered out at the macroscale, and therefore may represent a neuronal signature that could be used for microscale interventional strategies. This thesis demonstrates the utility of studying multi-scale dynamics in the larval zebrafish, to link neuronal activity at the microscale with emergent properties during seizures

The role of interoception in cognition, and its application to autism spectrum disorders

Traditionally a distinction was drawn between cognitive and sensorimotor processes, with little consideration of communication between the two. However, many findings are incompatible with this separation (e.g. Lebedev & Wise, 2002; Patel, Fleming & Kilner, 2012). One particular domain where this is evidenced is interoception. Interoception has been defined as the sensing of the physiological condition of the body (Craig, 2002). While it has long been clear that interoception is of fundamental importance for homeostasis, it is increasingly being recognised as integral for multiple domains of cognition, including emotion. For example, those with greater access to their interoceptive states experience emotions more intensely (e.g. Wiens, Mezzacappa, & Katkin, 2000). These findings bare on our understanding of autism. For some time, exteroceptive sensory abnormalities has been recognised in autism, with such symptoms now included in the diagnostic criteria. Far less research has considered how interoception is implicated in autism. The reports of autistic people and their caregivers, in addition to a few empirical investigations, suggest that interoceptive processing is altered in autism. It is therefore possible that these interoceptive alterations are implicated in the cognitive symptoms of autism. In this PhD I conducted a series of experiments to test the hypothesis that afferent signals from the body, including interoceptive sensations, are involved in cognition, and that the processing of these signals is altered in autism. More specifically, I tested the role of bodily afferents in metacognition, movement, anxiety, and emotion. I also sought to determine if there are interoceptive differences in the three domains of interoception delineated by Garfinkel and colleagues (Garfinkel & Critchley, 2013; Garfinkel, Seth, Barrett, Suzuki, & Critchley, 2015) in autistic children and adolescents, having previously only been evaluated previously in autistic adults. Finally, I investigated whether differences in emotion processing in autism were related to interoception

AN EDGE-CENTRIC PERSPECTIVE FOR BRAIN NETWORK COMMUNITIES

Thesis (Ph.D.) - Indiana University, Department of Psychological and Brain Sciences and Program in Neuroscience, 2021The brain is a complex system organized on multiple scales and operating in both a local and distributed manner. Individual neurons and brain regions participate in specific functions, while at the same time existing in the context of a larger network, supporting a range of different functionalities. Building brain networks comprised of distinct neural elements (nodes) and their interrelationships (edges), allows us to model the brain from both local and global perspectives, and to deploy a wide array of computational network tools. A popular network analysis approach is community detection, which aims to subdivide a network’s nodes into clusters that can used to represent and evaluate network organization. Prevailing community detection approaches applied to brain networks are designed to find densely interconnected sets of nodes, leading to the notion that the brain is organized in an exclusively modular manner. Furthermore, many brain network analyses tend to focus on the nodes, evidenced by the search for modular groupings of neural elements that might serve a common function. In this thesis, we describe the application of community detection algorithms that are sensitive to alternative cluster configurations, enhancing our understanding of brain network organization. We apply a framework called the stochastic block model, which we use to uncover evidence of non-modular organization in human anatomical brain networks across the life span, and in the informatically-collated rat cerebral cortex. We also propose a framework to cluster functional brain network edges in human data, which naturally results in an overlapping organization at the level of nodes that bridges canonical functional systems. These alternative methods utilize the connection patterns of brain network edges in ways that prevailing approaches do not. Thus, we motivate an alternative outlook which focuses on the importance of information provided by the brain’s interconnections, or edges. We call this an edge-centric perspective. The edge-centric approaches developed here offer new ways to characterize distributed brain organization and contribute to a fundamental change in perspective in our thinking about the brain

Applications of multi-way analysis for characterizing paediatric electroencephalogram (EEG) recordings

This doctoral thesis outlines advances in multi-way analysis for characterizing electroencephalogram (EEG) recordings from a paediatric population, with the aim to describe new links between EEG data and changes in the brain. This entails establishing the validity of multi-way analysis as a framework for identifying developmental information at the individual and collective level. Multi-way analysis broadens matrix analysis to a multi-linear algebraic architecture to identify latent structural relationships in naturally occurring higher order (n-way) data, like EEG. We use the canonical polyadic decomposition (CPD) as a multi-way model to efficiently express the complex structures present in paediatric EEG recordings as unique combinations of low-rank matrices, offering new insights into child development. This multi-way CPD framework is explored for both typically developing (TD) children and children with potential developmental delays (DD), e.g. children who suffer from epilepsy or paediatric stroke. Resting-state EEG (rEEG) data serves as an intuitive starting point in analyzing paediatric EEG via multi-way analysis. Here, the CPD model probes the underlying relationships between the spatial, spectral and subject modes of several rEEG datasets. We demonstrate the CPD can reveal distinct population-level features in rEEG that reflect unique developmental traits in varying child populations. These development-affiliated profiles are evaluated with respect to capturing structures well-established in childhood EEG. The identified features are also interrogated for their predictive abilities in anticipating new subjects’ ages. Assessing simulations and real rEEG datasets of TD and DD children establishes the multi-way analysis framework as well suited for identifying developmental profiles from paediatric rEEG. We extend the multi-way analysis scheme to more complex EEG scenarios common in EEG rehabilitation technology, like brain-computer interfaces. We explore the feasibility of multi-way modelling for interventions where developmental changes often pose as barriers. The multi-way CPD model is expanded to include four modes- task, spatial, spectral and subject data, with non-negativity and orthogonality constraints imposed. We analyze a visual attention task that elucidates a steady-state visual evoked potential and present the advantages gained from the extended CPD model. Through direct multi-linear projection, we demonstrate that linear profiles of the CPD can be capitalized upon for rapid task classification sans individual subject classifier calibration. Incorporating concepts from the multi-way analysis scheme with child development measured by psychometric tests, we propose the Joint EEG Development Inference (JEDI) model for inferring development from paediatric EEG. We utilize a common EEG task (button-press) to establish a 4-way CPD model of paediatric EEG data. Structured data fusion of the CPD model and cognitive scores from psychometric evaluations then permits joint decomposition of the two datasets to identify common features associated with each representation of development. Use of grid search optimization and a fully cross-validated design supports the JEDI model as another technique for rapidly discerning the developmental status of a child via EEG. We then briefly turn our attention to associating child development as measured by psychometric tests to markers in the EEG using graph network properties. Using graph networks, we show how the functional connectivity can inform on potential developmental delays in very young epileptic children using routine, clinical rEEG measures. This establishes a potential tool complementary to the JEDI model for identifying and inferring links between the established psychometric evaluation of developing children and functional analysis of the EEG. Multi-way analysis of paediatric EEG data offers a new approach for handling the developmental status and profiles of children. The CPD model offers flexibility in terms of identifying development-related features, and can be integrated into EEG tasks common in rehabilitation paradigms. We aim for the multi-way framework and associated techniques pursued in this thesis to be integrated and adopted as a useful tool clinicians can use for characterizing paediatric development

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Characterisation of the Haemodynamic Response Function (HRF) in the neonatal brain using functional MRI

Background: Preterm birth is associated with a marked increase in the risk of later neurodevelopmental impairment. With the incidence rising, novel tools are needed to provide an improved understanding of the underlying pathology and better prognostic information. Functional Magnetic Resonance Imaging (fMRI) with Blood Oxygen Level Dependent (BOLD) contrast has the potential to add greatly to the knowledge gained through traditional MRI techniques. However, it has been rarely used with neonatal subjects due to difficulties in application and inconsistent results. Central to this is uncertainity regarding the effects of early brain development on the Haemodynamic Response Function (HRF), knowledge of which is fundamental to fMRI methodology and analysis. Hypotheses: (1) Well localised and positive BOLD functional responses can be identified in the neonatal brain. (2) The morphology of the neonatal HRF differs significantly during early human development. (3) The application of an age-appropriate HRF will improve the identification of functional responses in neonatal fMRI studies. Methods: To test these hypotheses, a systematic fMRI study of neonatal subjects was carried out using a custom made somatosensory stimulus, and an adapted study design and analysis pipeline. The neonatal HRF was then characterised using an event related study design. The potential future application of the findings was then tested in a series of small experiments. Results: Well localised and positive BOLD functional responses were identified in neonatal subjects, with a maturational tendency towards an increasingly complex pattern of activation. A positive amplitude HRF was identified in neonatal subjects, with a maturational trend of a decreasing time-to-peak and increasing positive peak amplitude. Application of the empirical HRF significantly improved the precision of analysis in further fMRI studies. Conclusions: fMRI can be used to study functional activity in the neonatal brain, and may provide vital new information about both development and pathology