Pattern recognition and machine learning for magnetic resonance images with kernel methods

The aim of this thesis is to apply a particular category of machine learning and pattern recognition algorithms, namely the kernel methods, to both functional and anatomical magnetic resonance images (MRI). This work specifically focused on supervised learning methods. Both methodological and practical aspects are described in this thesis. Kernel methods have the computational advantage for high dimensional data, therefore they are idea for imaging data. The procedures can be broadly divided into two components: the construction of the kernels and the actual kernel algorithms themselves. Pre-processed functional or anatomical images can be computed into a linear kernel or a non-linear kernel. We introduce both kernel regression and kernel classification algorithms in two main categories: probabilistic methods and non-probabilistic methods. For practical applications, kernel classification methods were applied to decode the cognitive or sensory states of the subject from the fMRI signal and were also applied to discriminate patients with neurological diseases from normal people using anatomical MRI. Kernel regression methods were used to predict the regressors in the design of fMRI experiments, and clinical ratings from the anatomical scans

Resting-state Connectivity Dynamics in the Human Brain using High-speed fMRI

Resting-state fMRI using seed-based connectivity analysis (SCA) typically involves regression of the confounding signals resulting from movement and physiological noise sources. This not only adds additional complexity to the analysis but may also introduce possible regression bias. We recently introduced a computationally efficient real-time SCA approach without confound regression, which employs sliding-window correlation analysis with running mean and standard deviation (meta-statistics). The present study characterizes the confound tolerance of this windowed seed-based connectivity analysis (wSCA), which combines efficient decorrelation of confounding signal events with high-pass filter characteristics that reduce sensitivity to drifts. The confound suppression and the strength of resting-state network (RSN) connectivity were characterized for a range of confounding signal profiles as a function of sliding-window width and scan duration, using simulation and in vivo data. The connectivity strength in six resting-state networks (RSNs) and artifactual connectivity in white matter were compared between wSCA and conventional regression-based SCA (cSCA). The wSCA approach demonstrated scalable confound suppression that increased with decreasing sliding-window width and increasing scan duration in both simulations and in vivo. The confound suppression for sliding-window widths ≤ 15 s was comparable to that of cSCA. Twenty-eight RSNs that were previously reported in a group-ICA study were detected in real-time at scan durations as short as 30 s and with sliding-window widths as short as 4 s. The inter- and intra- network connectivity dynamics of the 28 resting-state networks were studied in real-time and self-repeating connectivity patterns were identified. The wSCA is further investigated offline to study the strength and temporal fluctuations in connectivity using 28 single-region seeds and 28 multi-region seed clusters to measure inter-regional connectivity (IRC) in 140 functional brain regions and inter-network connectivity (INC) among the hubs of 28 RSNs. Multi-region seed IRC maps displayed smaller temporal fluctuations and stronger resting-state connectivity compared with single-region seed IRC maps. Dual thresholding of the meta-statistics maps demonstrated higher spatio-temporal IRC stability in auditory, sensorimotor, and visual cortices compared to other brain regions. The group averaged INC matrices for single-region seeds were consistent with the functional network connectivity matrices (FNCMs) presented in the aforementioned group-ICA study. Furthermore, we extended the mapping of functional connectivity to the whole-brain connectivity fingerprints. In combination with novel brain parcellation methods and advanced machine learning algorithms, wSCA can aid in studying the spatial and temporal connectivity dynamics of the resting-state connectivity. The robust confound tolerance, high temporal resolution, and compatibility with real-time high-speed fMRI, make this approach suitable for monitoring data quality, neurofeedback, and clinical research studies involving disease related changes in functional connectomics

Assessing Preprocessing Methods and Software Tools for Functional Connectivity Analysis

This thesis presents an introductory exploration of the neuroimaging field, focusing on volume-based analysis using functional connectivity. By studying resting state data using the Power et al. atlas, the research aims to uncover patterns and relationships between brain regions, employing a qualitative study design with a single subject. DPABI Toolbox and Connectome Workbench were used to conduct volume-based functional connectivity analyses. DPABI Toolbox was used to preprocess and perform resting state analysis on the Human Connectome Project (HCP) raw data to produce a functional connectivity matrix. Connectome Workbench was used to create a pipeline for creating a resting state functional connectivity matrix. The resting state analysis was performed on the raw data preprocessed by DPABI and the preprocessed data provided by HCP. The resting state analyses performed on the same data preprocessed by DPABI yielded visually indistinguishable matrices. The similarity metrics further corroborated this observation, indicating no significant dissimilarities. The application of DPABI for preprocessing and resting state analysis was compared with a self-made pipeline utilizing preprocessed data from the HCP. The resting state analyses yielded two matrices that exhibited noticeable differences in their overall intensities, despite sharing a similar structure. The similarity metrics confirmed these distinctions, as they recorded lower values, indicating a dissimilarity between the matrices

Multivariate detrending of fMRI signal drifts for real-time multiclass pattern classification

Signal drift in functional magnetic resonance imaging (fMRI) is an unavoidable artifact that limits classification performance in multi-voxel pattern analysis of fMRI. As conventional methods to reduce signal drift, global demeaning or proportional scaling disregards regional variations of drift, whereas voxel-wise univariate detrending is too sensitive to noisy fluctuations. To overcome these drawbacks, we propose a multivariate real-time detrending method for multiclass classification that involves spatial demeaning at each scan and the recursive detrending of drifts in the classifier outputs driven by a multiclass linear support vector machine. Experiments using binary and multiclass data showed that the linear trend estimation of the classifier output drift for each class (a weighted sum of drifts in the class-specific voxels) was more robust against voxel-wise artifacts that lead to inconsistent spatial patterns and the effect of online processing than voxel-wise detrending. The classification performance of the proposed method was significantly better, especially for multiclass data, than that of voxel-wise linear detrending, global demeaning, and classifier output detrending without demeaning. We concluded that the multivariate approach using classifier output detrending of fMRI signals with spatial demeaning preserves spatial patterns, is less sensitive than conventional methods to sample size, and increases classification performance, which is a useful feature for real-time fMRI classification.ope

Functional Brain Organization in Space and Time

The brain is a network functionally organized at many spatial and temporal scales. To understand how the brain processes information, controls behavior and dynamically adapts to an ever-changing environment, it is critical to have a comprehensive description of the constituent elements of this network and how relationships between these elements may change over time. Decades of lesion studies, anatomical tract-tracing, and electrophysiological recording have given insight into this functional organization. Recently, however, resting state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for whole-brain non-invasive measurement of spontaneous neural activity in humans, giving ready access to macroscopic scales of functional organization previously much more difficult to obtain. This thesis aims to harness the unique combination of spatial and temporal resolution provided by functional MRI to explore the spatial and temporal properties of the functional organization of the brain. First, we establish an approach for defining cortical areas using transitions in correlated patterns of spontaneous BOLD activity (Chapter 2). We then propose and apply measures of internal and external validity to evaluate the credibility of the areal parcellation generated by this technique (Chapter 3). In chapter 4, we extend the study of functional brain organization to a highly sampled individual. We describe the idiosyncratic areal and systems-level organization of the individual relative to a standard group-average description. Further, we develop a model describing the reliability of BOLD correlation estimates across days that accounts for relevant sources of variability. Finally, in Chapter 5, we examine whether BOLD correlations meaningfully vary over the course of single resting-state scans

Frameworks to Investigate Robustness and Disease Characterization/Prediction Utility of Time-Varying Functional Connectivity State Profiles of the Human Brain at Rest

Neuroimaging technologies aim at delineating the highly complex structural and functional organization of the human brain. In recent years, several unimodal as well as multimodal analyses of structural MRI (sMRI) and functional MRI (fMRI) neuroimaging modalities, leveraging advanced signal processing and machine learning based feature extraction algorithms, have opened new avenues in diagnosis of complex brain syndromes and neurocognitive disorders. Generically regarding these neuroimaging modalities as filtered, complimentary insights of brain’s anatomical and functional organization, multimodal data fusion efforts could enable more comprehensive mapping of brain structure and function. Large scale functional organization of the brain is often studied by viewing the brain as a complex, integrative network composed of spatially distributed, but functionally interacting, sub-networks that continually share and process information. Such whole-brain functional interactions, also referred to as patterns of functional connectivity (FC), are typically examined as levels of synchronous co-activation in the different functional networks of the brain. More recently, there has been a major paradigm shift from measuring the whole-brain FC in an oversimplified, time-averaged manner to additional exploration of time-varying mechanisms to identify the recurring, transient brain configurations or brain states, referred to as time-varying FC state profiles in this dissertation. Notably, prior studies based on time-varying FC approaches have made use of these relatively lower dimensional fMRI features to characterize pathophysiology and have also been reported to relate to demographic characterization, consciousness levels and cognition. In this dissertation, we corroborate the efficacy of time-varying FC state profiles of the human brain at rest by implementing statistical frameworks to evaluate their robustness and statistical significance through an in-depth, novel evaluation on multiple, independent partitions of a very large rest-fMRI dataset, as well as extensive validation testing on surrogate rest-fMRI datasets. In the following, we present a novel data-driven, blind source separation based multimodal (sMRI-fMRI) data fusion framework that uses the time-varying FC state profiles as features from the fMRI modality to characterize diseased brain conditions and substantiate brain structure-function relationships. Finally, we present a novel data-driven, deep learning based multimodal (sMRI-fMRI) data fusion framework that examines the degree of diagnostic and prognostic performance improvement based on time-varying FC state profiles as features from the fMRI modality. The approaches developed and tested in this dissertation evince high levels of robustness and highlight the utility of time-varying FC state profiles as potential biomarkers to characterize, diagnose and predict diseased brain conditions. As such, the findings in this work argue in favor of the view of FC investigations of the brain that are centered on time-varying FC approaches, and also highlight the benefits of combining multiple neuroimaging data modalities via data fusion

Intelligent Biosignal Processing in Wearable and Implantable Sensors

This reprint provides a collection of papers illustrating the state-of-the-art of smart processing of data coming from wearable, implantable or portable sensors. Each paper presents the design, databases used, methodological background, obtained results, and their interpretation for biomedical applications. Revealing examples are brain–machine interfaces for medical rehabilitation, the evaluation of sympathetic nerve activity, a novel automated diagnostic tool based on ECG data to diagnose COVID-19, machine learning-based hypertension risk assessment by means of photoplethysmography and electrocardiography signals, Parkinsonian gait assessment using machine learning tools, thorough analysis of compressive sensing of ECG signals, development of a nanotechnology application for decoding vagus-nerve activity, detection of liver dysfunction using a wearable electronic nose system, prosthetic hand control using surface electromyography, epileptic seizure detection using a CNN, and premature ventricular contraction detection using deep metric learning. Thus, this reprint presents significant clinical applications as well as valuable new research issues, providing current illustrations of this new field of research by addressing the promises, challenges, and hurdles associated with the synergy of biosignal processing and AI through 16 different pertinent studies. Covering a wide range of research and application areas, this book is an excellent resource for researchers, physicians, academics, and PhD or master students working on (bio)signal and image processing, AI, biomaterials, biomechanics, and biotechnology with applications in medicine

A Hybrid Brain-Computer Interface Based on Electroencephalography and Functional Transcranial Doppler Ultrasound

Hybrid brain computer interfaces (BCIs) combining multiple brain imaging modalities have been proposed recently to boost the performance of single modality BCIs. We advance the state of hybrid BCIs by introducing a novel system that measures electrical brain activity as well as cerebral blood flow velocity using Electroencephalography (EEG) and functional transcranial Doppler ultrasound (fTCD), respectively. The system we developed employs two different paradigms to induce changes simultaneously in EEG and fTCD and to infer user intent. One of these paradigms includes visual stimuli to simultaneously induce steady state visually evoked potentials (SSVEPs) and instructs users to perform word generation (WG) and mental rotation (MR) tasks, while the other paradigm instructs users to perform left and right arm motor imagery (MI) tasks through visual stimuli. To improve accuracy and information transfer rate (ITR) of the proposed system compared to those obtained through our preliminary analysis, using classical feature extraction approaches, we mainly contribute to multi-modal fusion of EEG and fTCD features. Specifically, we proposed a probabilistic fusion of EEG and fTCD evidences instead of simple concatenation of EEG and fTCD feature vectors that we performed in our preliminary analysis. Experimental results showed that the MI paradigm outperformed the MR/WG one in terms of both accuracy and ITR. In particular, 93.85%, 93.71%, and 100% average accuracies and 19.89, 26.55, and 40.83 bits/min v average ITRs were achieved for right MI vs baseline, left MI versus baseline, and right MI versus left MI, respectively. Moreover, for both paradigms, the EEG-fTCD BCI with the proposed analysis techniques outperformed all EEG- fNIRS BCIs in terms of accuracy and ITR. In addition, to investigate the feasibility of increasing the possible number of BCI commands, we extended our approaches to solve the 3-class problems for both paradigms. It was found that the MI paradigm outperformed the MR/WG paradigm and achieved 96.58% average accuracy and 45 bits/min average ITR. Finally, we introduced a transfer learning approach to reduce the calibration requirements of the proposed BCI. This approach was found to be very efficient especially with the MI paradigm as it reduced the calibration requirements by at least 60.43%

Trajectory Data Mining in Mouse Models of Stroke

Contains fulltext : 273912.pdf (Publisher’s version ) (Open Access)Radboud University, 04 oktober 2022Promotor : Kiliaan, A.J. Co-promotor : Wiesmann, M.167 p

Multimodal assessment of emotional responses by physiological monitoring: novel auditory and visual elicitation strategies in traditional and virtual reality environments

This doctoral thesis explores novel strategies to quantify emotions and listening effort through monitoring of physiological signals. Emotions are a complex aspect of the human experience, playing a crucial role in our survival and adaptation to the environment. The study of emotions fosters important applications, such as Human-Computer and Human-Robot interaction or clinical assessment and treatment of mental health conditions such as depression, anxiety, stress, chronic anger, and mood disorders. Listening effort is also an important area of study, as it provides insight into the listeners’ challenges that are usually not identified by traditional audiometric measures. The research is divided into three lines of work, each with a unique emphasis on the methods of emotion elicitation and the stimuli that are most effective in producing emotional responses, with a specific focus on auditory stimuli. The research fostered the creation of three experimental protocols, as well as the use of an available online protocol for studying emotional responses including monitoring of both peripheral and central physiological signals, such as skin conductance, respiration, pupil dilation, electrocardiogram, blood volume pulse, and electroencephalography. An emotional protocol was created for the study of listening effort using a speech-in-noise test designed to be short and not induce fatigue. The results revealed that the listening effort is a complex problem that cannot be studied with a univariate approach, thus necessitating the use of multiple physiological markers to study different physiological dimensions. Specifically, the findings demonstrate a strong association between the level of auditory exertion, the amount of attention and involvement directed towards stimuli that are readily comprehensible compared to those that demand greater exertion. Continuing with the auditory domain, peripheral physiological signals were studied in order to discriminate four emotions elicited in a subject who listened to music for 21 days, using a previously designed and publicly available protocol. Surprisingly, the processed physiological signals were able to clearly separate the four emotions at the physiological level, demonstrating that music, which is not typically studied extensively in the literature, can be an effective stimulus for eliciting emotions. Following these results, a flat-screen protocol was created to compare physiological responses to purely visual, purely auditory, and combined audiovisual emotional stimuli. The results show that auditory stimuli are more effective in separating emotions at the physiological level. The subjects were found to be much more attentive during the audio-only phase. In order to overcome the limitations of emotional protocols carried out in a laboratory environment, which may elicit fewer emotions due to being an unnatural setting for the subjects under study, a final emotional elicitation protocol was created using virtual reality. Scenes similar to reality were created to elicit four distinct emotions. At the physiological level, it was noted that this environment is more effective in eliciting emotions. To our knowledge, this is the first protocol specifically designed for virtual reality that elicits diverse emotions. Furthermore, even in terms of classification, the use of virtual reality has been shown to be superior to traditional flat-screen protocols, opening the doors to virtual reality for the study of conditions related to emotional control