Tracking Rhythmicity in Biomedical Signals using Sequential Monte Carlo methods

Cyclical patterns are common in signals that originate from natural systems such as the human body and man-made machinery. Often these cyclical patterns are not perfectly periodic. In that case, the signals are called pseudo-periodic or quasi-periodic and can be modeled as a sum of time-varying sinusoids, whose frequencies, phases, and amplitudes change slowly over time. Each time-varying sinusoid represents an individual rhythmical component, called a partial, that can be characterized by three parameters: frequency, phase, and amplitude. Quasi-periodic signals often contain multiple partials that are harmonically related. In that case, the frequencies of other partials become exact integer multiples of that of the slowest partial. These signals are referred to as multi-harmonic signals. Examples of such signals are electrocardiogram (ECG), arterial blood pressure (ABP), and human voice. A Markov process is a mathematical model for a random system whose future and past states are independent conditional on the present state. Multi-harmonic signals can be modeled as a stochastic process with the Markov property. The Markovian representation of multi-harmonic signals enables us to use state-space tracking methods to continuously estimate the frequencies, phases, and amplitudes of the partials. Several research groups have proposed various signal analysis methods such as hidden Markov Models (HMM), short time Fourier transform (STFT), and Wigner-Ville distribution to solve this problem. Recently, a few groups of researchers have proposed Monte Carlo methods which estimate the posterior distribution of the fundamental frequency in multi-harmonic signals sequentially. However, multi-harmonic tracking is more challenging than single-frequency tracking, though the reason for this has not been well understood. The main objectives of this dissertation are to elucidate the fundamental obstacles to multi-harmonic tracking and to develop a reliable multi-harmonic tracker that can track cyclical patterns in multi-harmonic signals

Analysis of variations in diesel engine idle vibration

The variations in diesel engine idle vibration caused by fuels of different composition and their contributions to the variations in steering wheel vibrations were assessed. The time-varying covariance method (TV-AutoCov) and time-frequency continuous wavelet transform (CWT) techniques were used to obtain the cyclic and instantaneous characteristics of the vibration data acquired from two turbocharged four-cylinder, four-stroke diesel engine vehicles at idle under 12 different fuel conditions. The analysis revealed that TV-AutoCov analysis was the most effective for detecting changes in cycle-to-cycle combustion energy (22.61 per cent), whereas changes in the instantaneous Values of the combustion peaks were best measured using the CWT method (2.47 per cent). On the other hand, both methods showed that diesel idle vibration was more affected by amplitude modulation ( 12.54 per cent) than frequency modulation (4.46 per cent). The results of this work suggest the use of amplitude modulated signals for studying the human subjective response to diesel idle vibration at the steering wheel in passenger cars

Modeling complex cell regulation in the zebrafish circadian clock

The interdisciplinary "systems biology" approach of combining traditional biological investigations with tools from the mathematical and computer sciences has enabled novel insights into many highly complex and dynamic biological systems. The use of models has, for instance, revealed much about the intricate feedback mechanisms and acute importance of gene regulatory networks, and one such network of special note is our internal time keeper, or circadian clock. The circadian clock plays a pivotal role in modulating critical physiological processes, and has also been implicated, either directly or indirectly, in a whole range of pathological states. This research project investigates how the underlying dynamics of the circadian clock in the zebrafish model organism may be captured by a mathematical model, considering in particular the entrainment effect due to external cues such as light. Simulated data is contrasted with experimental results from different light regime experiments to validate the model and guide its refinement. Furthermore, various statistical methods are implemented to process the raw data and support its analysis. Extending the initial deterministic approach to take into account stochastic effects and additive population level effects emerges as a powerful means of representing the circadian signal decay in prolonged darkness, as well as light initiated re-synchronization as a strong component of entrainment. Consequently, it emerges that stochastic effects may be considered an essential feature of the circadian clock in zebrafish. A further cornerstone of the project is the implementation of an integrated simulation environment, including a Sequential Monte Carlo parameter estimation function, which succeeds in predicting a range of previously determined and also novel suitable parameter values. However, considerable difficulties in obtaining parameter values that satisfy the entire range of important target values simultaneously highlights the inherent complexity of accurately simulating the circadian clock

Imaging photoplethysmography: towards effective physiological measurements

Since its conception decades ago, Photoplethysmography (PPG) the non-invasive opto-electronic technique that measures arterial pulsations in-vivo has proven its worth by achieving and maintaining its rank as a compulsory standard of patient monitoring. However successful, conventional contact monitoring mode is not suitable in certain clinical and biomedical situations, e.g., in the case of skin damage, or when unconstrained movement is required. With the advance of computer and photonics technologies, there has been a resurgence of interest in PPG and one potential route to overcome the abovementioned issues has been increasingly explored, i.e., imaging photoplethysmography (iPPG). The emerging field of iPPG offers some nascent opportunities in effective and comprehensive interpretation of the physiological phenomena, indicating a promising alternative to conventional PPG. Heart and respiration rate, perfusion mapping, and pulse rate variability have been accessed using iPPG. To effectively and remotely access physiological information through this emerging technique, a number of key issues are still to be addressed. The engineering issues of iPPG, particularly the influence of motion artefacts on signal quality, are addressed in this thesis, where an engineering model based on the revised Beer-Lambert law was developed and used to describe opto-physiological phenomena relevant to iPPG. An iPPG setup consisting of both hardware and software elements was developed to investigate its reliability and reproducibility in the context of effective remote physiological assessment. Specifically, a first study was conducted for the acquisition of vital physiological signs under various exercise conditions, i.e. resting, light and heavy cardiovascular exercise, in ten healthy subjects. The physiological parameters derived from the images captured by the iPPG system exhibited functional characteristics comparable to conventional contact PPG, i.e., maximum heart rate difference was <3 bpm and a significant (p < 0.05) correlation between both measurements were also revealed. Using a method for attenuation of motion artefacts, the heart rate and respiration rate information was successfully assessed from different anatomical locations even in high-intensity physical exercise situations. This study thereby leads to a new avenue for noncontact sensing of vital signs and remote physiological assessment, showing clear and promising applications in clinical triage and sports training. A second study was conducted to remotely assess pulse rate variability (PRV), which has been considered a valuable indicator of autonomic nervous system (ANS) status. The PRV information was obtained using the iPPG setup to appraise the ANS in ten normal subjects. The performance of the iPPG system in accessing PRV was evaluated via comparison with the readings from a contact PPG sensor. Strong correlation and good agreement between these two techniques verify the effectiveness of iPPG in the remote monitoring of PRV, thereby promoting iPPG as a potential alternative to the interpretation of physiological dynamics related to the ANS. The outcomes revealed in the thesis could present the trend of a robust non-contact technique for cardiovascular monitoring and evaluation

Biomarker discovery and statistical modeling with applications in childhood epilepsy and Angelman syndrome

Biomarker discovery and statistical modeling reveals the brain activity that supports brain function and dysfunction. Detecting abnormal brain activity is critical for developing biomarkers of disease, elucidating disease mechanisms and evolution, and ultimately improving disease course. In my thesis, we develop statistical methodology to characterize neural activity in disease from noisy electrophysiological recordings. First, we develop a modification of a classic statistical modeling approach - multivariate Granger causality - to infer coordinated activity between brain regions. Assuming the signaling dependencies vary smoothly, we propose to write the history terms in autoregressive models of the signals using a lower dimensional spline basis. This procedure requires fewer parameters than the standard approach, thus increasing the statistical power. we show that this procedure accurately estimates brain dynamics in simulations and examples of physiological recordings from a patient with pharmacoresistant epilepsy. This work provides a statistical framework to understand alternations in coordinated brain activity in disease. Second, we demonstrate that sleep spindles, thalamically-driven neural rhythms (9-15 Hz) associated with sleep-dependent learning, are a reliable biomarker for Rolandic epilepsy. Rolandic epilepsy is the most common form of childhood epilepsy and characterized by nocturnal focal epileptic discharges as well as neurocognitive deficits. We show that sleep spindle rate is reduced regionally across cortex and correlated with poor cognitive performance in epilepsy. These results provide evidence for a regional disruption to the thalamocortical circuit in Rolandic epilepsy, and a potential mechanistic explanation for the cognitive deficits observed. Finally, we develop a procedure to utilize delta rhythms (2-4 Hz), a sensitive biomarker for Angelman syndrome, as a non-invasive measure of treatment efficacy in clinical trials. Angelman syndrome is a rare neurodevelopmental disorder caused by reduced expression of the UBE3A protein. Many disease-modifying treatments are being developed to reinstate UBE3A expression. To aid in clinical trials, we propose a procedure that detects therapeutic improvements in delta power outside of the natural variability over age by developing a longitudinal natural history model of delta power. These results demonstrate the utility of biomarker discovery and statistical modeling for elucidating disease course and mechanisms with the long-term goal of improving patient outcomes

Abstracts on Radio Direction Finding (1899 - 1995)

The files on this record represent the various databases that originally composed the CD-ROM issue of "Abstracts on Radio Direction Finding" database, which is now part of the Dudley Knox Library's Abstracts and Selected Full Text Documents on Radio Direction Finding (1899 - 1995) Collection. (See Calhoun record https://calhoun.nps.edu/handle/10945/57364 for further information on this collection and the bibliography). Due to issues of technological obsolescence preventing current and future audiences from accessing the bibliography, DKL exported and converted into the three files on this record the various databases contained in the CD-ROM. The contents of these files are: 1) RDFA_CompleteBibliography_xls.zip [RDFA_CompleteBibliography.xls: Metadata for the complete bibliography, in Excel 97-2003 Workbook format; RDFA_Glossary.xls: Glossary of terms, in Excel 97-2003 Workbookformat; RDFA_Biographies.xls: Biographies of leading figures, in Excel 97-2003 Workbook format]; 2) RDFA_CompleteBibliography_csv.zip [RDFA_CompleteBibliography.TXT: Metadata for the complete bibliography, in CSV format; RDFA_Glossary.TXT: Glossary of terms, in CSV format; RDFA_Biographies.TXT: Biographies of leading figures, in CSV format]; 3) RDFA_CompleteBibliography.pdf: A human readable display of the bibliographic data, as a means of double-checking any possible deviations due to conversion

Digital Biomarker Models for Prediction of Infectious Disease Susceptibility

Acute respiratory viral infection (ARVI) represents one of the most prevalent infectious diseases affecting mankind. With the threat of COVID-19 still looming over us, we have witnessed the substantial threat ARVI poses to world health and economy, extinguishing millions of lives and costing trillions of dollars. This sets the context for the research of this thesis: using digital biomarkers to distinguish between individuals who are susceptible to becoming severely infected and/or infectious before an infection is clinically detectable. The development of such biomarkers can have both clinical and epidemiological impact in terms of identifying individuals who are either vulnerable to severe infection or those who may become highly infectious. The digital biomarkers and associated analysis methods are developed and validated on longitudinal data collected by our clinical collaborators from two different ARVI challenge studies. The first study provides data on healthy human volunteers who were inoculated with the common cold and the second study provides data on volunteers inoculated with the flu. Digital biomarkers include molecular, physiological and cognitive data continuously collected from blood, wearable devices and cognitive testing of the study participants. The findings of our research on digitally measurable susceptibility factors are wide-ranging. We find that circadian rhythm at the molecular scale (biochronicity) plays an important role in mediating both the susceptibility and the response to severe infection, revealing groups of gene expression markers that differentiate the responses of low infected and high infected individuals. Using a high dimensional representation of physiological signals from a wearable device, we find that an infection response and its onset time can be reliably predicted at least 24 hours before peak infection time. We find that a certain measure of variability in pre-exposure cognitive function is highly associated with the post-exposure severity of infection.PHDBioinformaticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169966/1/yayazhai_1.pd

Autonomic Nervous System Dynamics for Mood and Emotional-State Recognition: Wearable Systems, Modeling, and Advanced Biosignal Processing

This thesis aims at investigating how electrophysiological signals related to the autonomic nervous system (ANS) dynamics could be source of reliable and effective markers for mood state recognition and assessment of emotional responses. In-depth methodological and applicative studies of biosignals such as electrocardiogram, electrodermal response, and respiration activity along with information coming from the eyes (gaze points and pupil size variation) were performed. Supported by the current literature, I found that nonlinear signal processing techniques play a crucial role in understanding the underlying ANS physiology and provide important quantifiers of cardiovascular control dynamics with prognostic value in both healthy subjects and patients. Two main applicative scenarios were identified: the former includes a group of healthy subjects who was presented with sets of images gathered from the International Affective Picture System hav- ing five levels of arousal and five levels of valence, including both a neutral reference level. The latter was constituted by bipolar patients who were followed for a period of 90 days during which psychophysical evaluations were performed. In both datasets, standard signal processing techniques as well as nonlinear measures have been taken into account to automatically and accurately recognize the elicited levels of arousal and valence and mood states, respectively. A novel probabilistic approach based on the point-process theory was also successfully applied in order to model and characterize the instantaneous ANS nonlinear dynamics in both healthy subjects and bipolar patients. According to the reported evidences on ANS complex behavior, experimental results demonstrate that an accurate characterization of the elicited affective levels and mood states is viable only when non- linear information are retained. Moreover, I demonstrate that the instantaneous ANS assessment is effective in both healthy subjects and patients. Besides mathematics and signal processing, this thesis also contributes to pragmatic issues such as emotional and mood state mod- eling, elicitation, and noninvasive ANS monitoring. Throughout the dissertation, a critical review on the current state-of-the-art is reported leading to the description of dedicated experimental protocols, reliable mood models, and novel wearable systems able to perform ANS monitoring in a naturalistic environment

Models and Analysis of Vocal Emissions for Biomedical Applications

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies

29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202