A Constrained ICA-EMD Model for Group Level fMRI Analysis

Independent component analysis (ICA), being a data-driven method, has been shown to be a powerful tool for functional magnetic resonance imaging (fMRI) data analysis. One drawback of this multivariate approach is that it is not, in general, compatible with the analysis of group data. Various techniques have been proposed to overcome this limitation of ICA. In this paper, a novel ICA-based workflow for extracting resting-state networks from fMRI group studies is proposed. An empirical mode decomposition (EMD) is used, in a data-driven manner, to generate reference signals that can be incorporated into a constrained version of ICA (cICA), thereby eliminating the inherent ambiguities of ICA. The results of the proposed workflow are then compared to those obtained by a widely used group ICA approach for fMRI analysis. In this study, we demonstrate that intrinsic modes, extracted by EMD, are suitable to serve as references for cICA. This approach yields typical resting-state patterns that are consistent over subjects. By introducing these reference signals into the ICA, our processing pipeline yields comparable activity patterns across subjects in a mathematically transparent manner. Our approach provides a user-friendly tool to adjust the trade-off between a high similarity across subjects and preserving individual subject features of the independent components

A study of information-theoretic metaheuristics applied to functional neuroimaging datasets

This dissertation presents a new metaheuristic related to a two-dimensional ensemble empirical mode decomposition (2DEEMD). It is based on Green’s functions and is called Green’s Function in Tension - Bidimensional Empirical Mode Decomposition (GiT-BEMD). It is employed for decomposing and extracting hidden information of images. A natural image (face image) as well as images with artificial textures have been used to test and validate the proposed approach. Images are selected to demonstrate efficiency and performance of the GiT-BEMD algorithm in extracting textures on various spatial scales from the different images. In addition, a comparison of the performance of the new algorithm GiT-BEMD with a canonical BEEMD is discussed. Then, GiT-BEMD as well as canonical bidimensional EEMD (BEEMD) are applied to an fMRI study of a contour integration task. Thus, it explores the potential of employing GiT-BEMD to extract such textures, so-called bidimensional intrinsic mode functions (BIMFs), of functional biomedical images. Because of the enormous computational load and the artifacts accompanying the extracted textures when using a canonical BEEMD, GiT-BEMD is developed to cope with such challenges. It is seen that the computational cost is decreased dramatically, and the quality of the extracted textures is enhanced considerably. Consequently, GiT-BEMD achieves a higher quality of the estimated BIMFs as can be seen from a direct comparison of the results obtained with different variants of BEEMD and GiT-BEMD. Moreover, results generated by 2DBEEMD, especially in case of GiT-BEMD, distinctly show a superior precision in spatial localization of activity blobs when compared with a canonical general linear model (GLM) analysis employing statistical parametric mapping (SPM). Furthermore, to identify most informative textures, i.e. BIMFs, a support vector machine (SVM) as well as a random forest (RF) classifier is employed. Classification performance demonstrates the potential of the extracted BIMFs in supporting decision making of the classifier. With GiT-BEMD, the classification performance improved significantly which might also be a consequence of a clearer structure for these modes compared to the ones obtained with canonical BEEMD. Altogether, there is strong believe that the newly proposed metaheuristic GiT-BEMD offers a highly competitive alternative to existing BEMD algorithms and represents a promising technique for blindly decomposing images and extracting textures thereof which may be used for further analysis

NEW APPROACHES FOR ASSESSING TIME-VARYING FUNCTIONAL BRAIN CONNECTIVITY USING FMRI DATA

It was long assumed that functional connectivity (FC) among brain regions did not vary substantially during a single resting-state functional magnetic resonance imaging (rs-fMRI) run. However, an increasing number of studies have reported on the existence of time-varying functional connectivity (TVC) in rs-fMRI data taking place in a considerably shorter time window than previously thought (i.e., on the order of seconds and minutes). However, the study of TVFC is a relatively new research area and there remain a number of unaddressed problems hindering its ability to fulfill its promise of increasing our knowledge of human brain function. First, while it has previously been shown that autocorrelation can negatively impact estimates of static functional connectivity, its impact on TVC estimates has not been established. Understanding the influence of autocorrelation on TVFC is of high importance, as we hypothesize the autocorrelation within a time series can inflate the sampling variability of TVC estimated using sliding window techniques, leading to the increase of risk of misinterpreting noise as true TVC and negatively impact subsequent estimation of whole-brain time varying functional connectivity. We thus study the impact of autocorrelation on TVC and how to mitigate it. Second, there is a need for new analytic approaches for estimating TVC. Most studies use a sliding window approach, where the correlation between region is computed locally within a specific time window that is moved across time. A shortcoming of this approach is the need to select an a priori window length for analysis. To circumvent this issue, we focus on the use of instantaneous phase synchronization (IPS), which offers single time-point resolution of time-resolved fMRI connectivity. The use of IPS necessitates bandpass filtering the data to obtain valid results. We seek to show how bandpass filtering affects the estimates of IPS metrics such as phase locking value (PLV) and phase coherence. Further, as current metrics discard the temporal transitions from positive to negative associations common in IPS analysis we introduce a new approach within IPS framework for circumventing this issue. Third, the choice of cut-off frequencies when bandpass filtering in IPS analysis is to some extend arbitrary. We seek to compare standard phase synchronization using the Hilbert transform with empirical mode decomposition (EMD) which eliminates the need for bandpass filtering in a data driven manner. While the use of EMD has a number of benefits compared to the Hilbert transform, it has a couple shortcomings: the susceptibility of the EMD to the SNR of the signal and untangling frequencies close to one another. To circumvent this issue and improve the assessment of IPS, we propose the use of an alternative decomposition approach, multivariate variational mode decomposition (MVMD) for phase synchronization analysis.

Information processing in visual systems

One of the goals of neuroscience is to understand how animals perceive sensory information. This thesis focuses on visual systems, to unravel how neuronal structures process aspects of the visual environment. To characterise the receptive field of a neuron, we developed spike-triggered independent component analysis. Alongside characterising the receptive field of a neuron, this method provides an insight into its underlying network structure. When applied to recordings from the H1 neuron of blowflies, it accurately recovered the sub-structure of the neuron. This sub-structure was studied further by recording H1's response to plaid stimuli. Based on the response, H1 can be classified as a component cell. We then fitted an anatomically inspired model to the response, and found the critical component to explain H1's response to be a sigmoid non-linearity at output of elementary movement detectors. The simpler blowfly visual system can help us understand elementary sensory information processing mechanisms. How does the more complex mammalian cortex implement these principles in its network? To study this, we used multi-electrode arrays to characterise the receptive field properties of neurons in the visual cortex of anaesthetised mice. Based on these recordings, we estimated the cortical limits on the performance of a visual task; the behavioural performance observed by Prusky and Douglas (2004) is within these limits. Our recordings were carried out in anaesthetised animals. During anaesthesia, cortical UP states are considered "fragments of wakefulness" and from simultaneous whole-cell and extracellular recordings, we found these states to be revealed in the phase of local field potentials. This finding was used to develop a method of detecting cortical state based on extracellular recordings, which allows us to explore information processing during different cortical states. Across this thesis, we have developed, tested and applied methods that help improve our understanding of information processing in visual systems

Time resolved functional brain networks : a novel method and developmental perspective

Functional neuroimaging has helped elucidating the complexity of brain function in ever more detail during the last 30 years. In this time the concepts used to understand how the brain works has also developed from a focus on regional activation to a network based whole brain perspective (Deco et al., 2015). The understanding that the brain is not just merely responding to external demands but is itself a co-creator of its perceived reality is now the default perspective (Buzsáki and Fernández-Ruiz, 2019). This means that the brain is never resting and its intrinsic architecture is the basis for any task related modulation (Cole et al., 2014). As often in science, understanding and technological advances go hand in hand. For the advancement of the functional neuroimaging field during the last decade, methods that are able to track, capture and model time resolved connectivity changes has been essential (Lurie et al., 2020). This development is an ongoing process. Part of the work presented in this thesis is a small contribution to this collective endeavor. The first theme in the thesis is time resolved connectivity of functional brain networks. This theme is present in Study I which presents a novel method for analysis of time resolved connectivity using BOLD fMRI data. With this method, subnetworks in the brain are defined dynamically. It allows for connectivity changes to be tracked from time point to time point while respecting the temporal ordering of the data. It also provides relational properties in terms of differences in phase coherence between simultaneously integrated networks and their gradual change. The method can be used see how whole brain connectivity configurations recure in quasi-cyclic patterns. Finally, the method is able to estimate flexibility and modularity of individual brain areas. The method is applied in Study III in order to understand how premature birth effects flexibility and modularity of intrinsic functional brain networks. Beyond the purely scientific endeavor to understand how the brain creates cognition, consciousness, perception and supports motor function, neuroimaging research has also been helpful in elucidating normal brain development and neurodevelopmental disorders. The second theme in this thesis is brain development in extremely preterm born children at school age. This theme is the focus of Study II & III. Study II investigates the prevalence of discrete white matter abnormalities at school age in children born extremely preterm and the relationship to neuro-motor outcome. The prevalence of white matter abnormalities was high but there was no relationship to an unfavorable outcome. Also, a longitudinal association to neonatal white matter injury was seen. While discrete white matter abnormalities were not correlated to quantitative measures of white matter volume and white matter integrity, neonatal white matter injury was associated with lower volume and integrity at age 8- 11 years. Moreover, neonatal white matter injury was associated with lower processing speed at 12 years. The third and final study investigated flexibility and modularity as well as lateralization of intrinsic networks in children born extremely preterm at age 8-11 years. No significant differences in either flexibility or modularity was seen for any intrinsic network after correcting for multiple comparisons. However, at the level of individual brain areas, preterm children showed decreased flexibility in both the basal ganglia and thalamus. Also, children born extremely preterm had a decreased level of lateralization in most networks

Deep Interpretability Methods for Neuroimaging

Brain dynamics are highly complex and yet hold the key to understanding brain function and dysfunction. The dynamics captured by resting-state functional magnetic resonance imaging data are noisy, high-dimensional, and not readily interpretable. The typical approach of reducing this data to low-dimensional features and focusing on the most predictive features comes with strong assumptions and can miss essential aspects of the underlying dynamics. In contrast, introspection of discriminatively trained deep learning models may uncover disorder-relevant elements of the signal at the level of individual time points and spatial locations. Nevertheless, the difficulty of reliable training on high-dimensional but small-sample datasets and the unclear relevance of the resulting predictive markers prevent the widespread use of deep learning in functional neuroimaging. In this dissertation, we address these challenges by proposing a deep learning framework to learn from high-dimensional dynamical data while maintaining stable, ecologically valid interpretations. The developed model is pre-trainable and alleviates the need to collect an enormous amount of neuroimaging samples to achieve optimal training. We also provide a quantitative validation module, Retain and Retrain (RAR), that can objectively verify the higher predictability of the dynamics learned by the model. Results successfully demonstrate that the proposed framework enables learning the fMRI dynamics directly from small data and capturing compact, stable interpretations of features predictive of function and dysfunction. We also comprehensively reviewed deep interpretability literature in the neuroimaging domain. Our analysis reveals the ongoing trend of interpretability practices in neuroimaging studies and identifies the gaps that should be addressed for effective human-machine collaboration in this domain. This dissertation also proposed a post hoc interpretability method, Geometrically Guided Integrated Gradients (GGIG), that leverages geometric properties of the functional space as learned by a deep learning model. With extensive experiments and quantitative validation on MNIST and ImageNet datasets, we demonstrate that GGIG outperforms integrated gradients (IG), which is considered to be a popular interpretability method in the literature. As GGIG is able to identify the contours of the discriminative regions in the input space, GGIG may be useful in various medical imaging tasks where fine-grained localization as an explanation is beneficial

Functional Source Separation for EEG-fMRI Fusion: Application to Steady-State Visual Evoked Potentials

Neurorobotics is one of the most ambitious fields in robotics, driving integration of interdisciplinary data and knowledge. One of the most productive areas of interdisciplinary research in this area has been the implementation of biologically-inspired mechanisms in the development of autonomous systems. Specifically, enabling such systems to display adaptive behavior such as learning from good and bad outcomes, has been achieved by quantifying and understanding the neural mechanisms of the brain networks mediating adaptive behaviors in humans and animals. For example, associative learning from aversive or dangerous outcomes is crucial for an autonomous system, to avoid dangerous situations in the future. A body of neuroscience research has suggested that the neurocomputations in the human brain during associative learning involve re-shaping of sensory responses. The nature of these adaptive changes in sensory processing during learning however are not yet well enough understood to be readily implemented into on-board algorithms for robotics application. Toward this overall goal, we record the simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), characterizing one candidate mechanism, i.e., large-scale brain oscillations. The present report examines the use of Functional Source Separation (FSS) as an optimization step in EEG-fMRI fusion that harnesses timing information to constrain the solutions that satisfy physiological assumptions. We applied this approach to the voxel-wise correlation of steady-state visual evoked potential (ssVEP) amplitude and blood oxygen level-dependent imaging (BOLD), across both time series. The results showed the benefit of FSS for the extraction of robust ssVEP signals during simultaneous EEG-fMRI recordings. Applied to data from a 3-phase aversive conditioning paradigm, the correlation maps across the three phases (habituation, acquisition, extinction) show converging results, notably major overlapping areas in both primary and extended visual cortical regions, including calcarine sulcus, lingual cortex, and cuneus. In addition, during the acquisition phase when aversive learning occurs, we observed additional correlations between ssVEP and BOLD in the anterior cingulate cortex (ACC) as well as the precuneus and superior temporal gyrus

Using the General Linear Model to Improve Performance in fNIRS Single Trial Analysis and Classification: A Perspective

Within a decade, single trial analysis of functional Near Infrared Spectroscopy (fNIRS) signals has gained significant momentum, and fNIRS joined the set of modalities frequently used for active and passive Brain Computer Interfaces (BCI). A great variety of methods for feature extraction and classification have been explored using state-of-the-art Machine Learning methods. In contrast, signal preprocessing and cleaning pipelines for fNIRS often follow simple recipes and so far rarely incorporate the available state-of-the-art in adjacent fields. In neuroscience, where fMRI and fNIRS are established neuroimaging tools, evoked hemodynamic brain activity is typically estimated across multiple trials using a General Linear Model (GLM). With the help of the GLM, subject, channel, and task specific evoked hemodynamic responses are estimated, and the evoked brain activity is more robustly separated from systemic physiological interference using independent measures of nuisance regressors, such as short-separation fNIRS measurements. When correctly applied in single trial analysis, e.g., in BCI, this approach can significantly enhance contrast to noise ratio of the brain signal, improve feature separability and ultimately lead to better classification accuracy. In this manuscript, we provide a brief introduction into the GLM and show how to incorporate it into a typical BCI preprocessing pipeline and cross-validation. Using a resting state fNIRS data set augmented with synthetic hemodynamic responses that provide ground truth brain activity, we compare the quality of commonly used fNIRS features for BCI that are extracted from (1) conventionally preprocessed signals, and (2) signals preprocessed with the GLM and physiological nuisance regressors. We show that the GLM-based approach can provide better single trial estimates of brain activity as well as a new feature type, i.e., the weight of the individual and channel-specific hemodynamic response function (HRF) regressor. The improved estimates yield features with higher separability, that significantly enhance accuracy in a binary classification task when compared to conventional preprocessing—on average +7.4% across subjects and feature types. We propose to adapt this well-established approach from neuroscience to the domain of single-trial analysis and preprocessing wherever the classification of evoked brain activity is of concern, for instance in BCI

Statistical single channel source separation

PhD ThesisSingle channel source separation (SCSS) principally is one of the challenging fields in signal processing and has various significant applications. Unlike conventional SCSS methods which were based on linear instantaneous model, this research sets out to investigate the separation of single channel in two types of mixture which is nonlinear instantaneous mixture and linear convolutive mixture. For the nonlinear SCSS in instantaneous mixture, this research proposes a novel solution based on a two-stage process that consists of a Gaussianization transform which efficiently compensates for the nonlinear distortion follow by a maximum likelihood estimator to perform source separation. For linear SCSS in convolutive mixture, this research proposes new methods based on nonnegative matrix factorization which decomposes a mixture into two-dimensional convolution factor matrices that represent the spectral basis and temporal code. The proposed factorization considers the convolutive mixing in the decomposition by introducing frequency constrained parameters in the model. The method aims to separate the mixture into its constituent spectral-temporal source components while alleviating the effect of convolutive mixing. In addition, family of Itakura-Saito divergence has been developed as a cost function which brings the beneficial property of scale-invariant. Two new statistical techniques are proposed, namely, Expectation-Maximisation (EM) based algorithm framework which maximizes the log-likelihood of a mixed signals, and the maximum a posteriori approach which maximises the joint probability of a mixed signal using multiplicative update rules. To further improve this research work, a novel method that incorporates adaptive sparseness into the solution has been proposed to resolve the ambiguity and hence, improve the algorithm performance. The theoretical foundation of the proposed solutions has been rigorously developed and discussed in details. Results have concretely shown the effectiveness of all the proposed algorithms presented in this thesis in separating the mixed signals in single channel and have outperformed others available methods.Universiti Teknikal Malaysia Melaka(UTeM), Ministry of Higher Education of Malaysi