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

A Study of Biomedical Time Series Using Empirical Mode Decomposition : Extracting event-related modes from EEG signals recorded during visual processing of contour stimuli

Noninvasive neuroimaging techniques like functional Magnetic Resonance Imaging (fMRI) and/or Electroencephalography (EEG) allow researchers to investigate and analyze brain activities during visual processing. EEG offers a high temporal resolution at a level of submilliseconds which can be combined favorably with fMRI which has a good spatial resolution on small spatial scales in the millimeter range. These neuroimaging techniques were, and still are instrumental in the diagnoses and treatments of neurological disorders in the clinical applications. In this PhD thesis we concentrate on lectrophysiological signatures within EEG recordings of a combined EEG-fMRI data set which where taken while performing a contour integration task. The estimation of location and distribution of the electrical sources in the brain from surface recordings which are responsible for interesting EEG waves has drawn the attention of many EEG/MEG researchers. However, this process which is called brain source localization is still one of the major problems in EEG. It consists of solving two modeling problems: forward and inverse. In the forward problem, one is interested in predicting the expected potential distribution on the scalp from given electrical sources that represent active neurons in the head. These evaluations are necessary to solve the inverse problem which can be defined as the problem of estimating the brain sources that generated the measured electrical potentials. This thesis presents a data-driven analysis of EEG data recorded during a combined EEG/fMRI study of visual processing during a contour integration task. The analysis is based on an ensemble empirical mode decomposition (EEMD) and discusses characteristic features of event related modes (ERMs) resulting from the decomposition. We identify clear differences in certain ERMs in response to contour vs non-contour Gabor stimuli mainly for response amplitudes peaking around 100 [ms] (called P100) and 200 [ms] (called N200) after stimulus onset, respectively. We observe early P100 and N200 responses at electrodes located in the occipital area of the brain, while late P100 and N200 responses appear at electrodes located in frontal brain areas. Signals at electrodes in central brain areas show bimodal early/late response signatures in certain ERMs. Head topographies clearly localize statistically significant response differences to both stimulus conditions. Our findings provide an independent proof of recent models which suggest that contour integration depends on distributed network activity within the brain. Next and based on the previous analysis, a new approach for source localization of EEG data based on combining ERMs, extracted with EEMD, with inverse models has been presented. As the first step, 64 channel EEG recordings are pooled according to six brain areas and decomposed, by applying an EEMD, into their underlying ERMs. Then, based upon the problem at hand, the most closely related ERM, in terms of frequency and amplitude, is combined with inverse modeling techniques for source localization. More specifically, the standardized low resolution brain electromagnetic tomography (sLORETA) procedure is employed in this work. Accuracy and robustness of the results indicate that this approach deems highly promising in source localization techniques for EEG data. Given the results of analyses above, it can be said that EMD is able to extract intrinsic signal modes, ERMs, which contain decisive information about responses to contour and non-contour stimuli. Hence, we introduce a new toolbox, called EMDLAB, which serves the growing interest of the signal processing community in applying EMD as a decomposition technique. EMDLAB can be used to perform, easily and effectively, four common types of EMD: plain EMD, ensemble EMD (EEMD), weighted sliding EMD (wSEMD) and multivariate EMD (MEMD) on the EEG data. The main goal of EMDLAB toolbox is to extract characteristics of either the EEG signal by intrinsic mode functions (IMFs) or ERMs. Since IMFs reflect characteristics of the original EEG signal, ERMs reflect characteristics of ERPs of the original signal. The new toolbox is provided as a plug-in to the well-known EEGLAB which enables it to exploit the advantageous visualization capabilities of EEGLAB as well as statistical data analysis techniques provided there for extracted IMFs and ERMs of the signal

Heterogeneous data fusion for brain psychology applications

This thesis aims to apply Empirical Mode Decomposition (EMD), Multiscale Entropy (MSE), and collaborative adaptive filters for the monitoring of different brain consciousness states. Both block based and online approaches are investigated, and a possible extension to the monitoring and identification of Electromyograph (EMG) states is provided. Firstly, EMD is employed as a multiscale time-frequency data driven tool to decompose a signal into a number of band-limited oscillatory components; its data driven nature makes EMD an ideal candidate for the analysis of nonlinear and non-stationary data. This methodology is further extended to process multichannel real world data, by making use of recent theoretical advances in complex and multivariate EMD. It is shown that this can be used to robustly measure higher order features in multichannel recordings to robustly indicate ‘QBD’. In the next stage, analysis is performed in an information theory setting on multiple scales in time, using MSE. This enables an insight into the complexity of real world recordings. The results of the MSE analysis and the corresponding statistical analysis show a clear difference in MSE between the patients in different brain consciousness states. Finally, an online method for the assessment of the underlying signal nature is studied. This method is based on a collaborative adaptive filtering approach, and is shown to be able to approximately quantify the degree of signal nonlinearity, sparsity, and non-circularity relative to the constituent subfilters. To further illustrate the usefulness of the proposed data driven multiscale signal processing methodology, the final case study considers a human-robot interface based on a multichannel EMG analysis. A preliminary analysis shows that the same methodology as that applied to the analysis of brain cognitive states gives robust and accurate results. The analysis, simulations, and the scope of applications presented suggest great potential of the proposed multiscale data processing framework for feature extraction in multichannel data analysis. Directions for future work include further development of real-time feature map approaches and their use across brain-computer and brain-machine interface applications

Data Analytics in Steady-State Visual Evoked Potential-based Brain-Computer Interface: A Review

Electroencephalograph (EEG) has been widely applied for brain-computer interface (BCI) which enables paralyzed people to directly communicate with and control of external devices, due to its portability, high temporal resolution, ease of use and low cost. Of various EEG paradigms, steady-state visual evoked potential (SSVEP)-based BCI system which uses multiple visual stimuli (such as LEDs or boxes on a computer screen) flickering at different frequencies has been widely explored in the past decades due to its fast communication rate and high signal-to-noise ratio. In this paper, we review the current research in SSVEP-based BCI, focusing on the data analytics that enables continuous, accurate detection of SSVEPs and thus high information transfer rate. The main technical challenges, including signal pre-processing, spectrum analysis, signal decomposition, spatial filtering in particular canonical correlation analysis and its variations, and classification techniques are described in this paper. Research challenges and opportunities in spontaneous brain activities, mental fatigue, transfer learning as well as hybrid BCI are also discussed

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

ARTIFACT CHARACTERIZATION, DETECTION AND REMOVAL FROM NEURAL SIGNALS

Ph.DDOCTOR OF PHILOSOPH

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

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.

Advances in Neural Signal Processing

Neural signal processing is a specialized area of signal processing aimed at extracting information or decoding intent from neural signals recorded from the central or peripheral nervous system. This has significant applications in the areas of neuroscience and neural engineering. These applications are famously known in the area of brain–machine interfaces. This book presents recent advances in this flourishing field of neural signal processing with demonstrative applications