Recovering Arrhythmic EEG Transients from Their Stochastic Interference

Traditionally, the neuronal dynamics underlying electroencephalograms (EEG) have been understood as arising from \textit{rhythmic oscillators with varying degrees of synchronization}. This dominant metaphor employs frequency domain EEG analysis to identify the most prominent populations of neuronal current sources in terms of their frequency and spectral power. However, emerging perspectives on EEG highlight its arrhythmic nature, which is primarily inferred from broadband EEG properties like the ubiquitous $1/f$ spectrum. In the present study, we use an \textit{arrhythmic superposition of pulses} as a metaphor to explain the origin of EEG. This conceptualization has a fundamental problem because the interference produced by the superpositions of pulses generates colored Gaussian noise, masking the temporal profile of the generating pulse. We solved this problem by developing a mathematical method involving the derivative of the autocovariance function to recover excellent approximations of the underlying pulses, significantly extending the analysis of this type of stochastic processes. When the method is applied to spontaneous mouse EEG sampled at $5$ kHz during the sleep-wake cycle, specific patterns -- called $\Psi$-patterns -- characterizing NREM sleep, REM sleep, and wakefulness are revealed. $\Psi$-patterns can be understood theoretically as \textit{power density in the time domain} and correspond to combinations of generating pulses at different time scales. Remarkably, we report the first EEG wakefulness-specific feature, which corresponds to an ultra-fast ($\sim 1$ ms) transient component of the observed patterns. By shifting the paradigm of EEG genesis from oscillators to random pulse generators, our theoretical framework pushes the boundaries of traditional Fourier-based EEG analysis, paving the way for new insights into the arrhythmic components of neural dynamics.Comment: Original research manuscript in PDF format, 46 pages long, with 13 figures and one tabl

State space methods for phase amplitude coupling analysis

Phase amplitude coupling (PAC) is thought to play a fundamental role in the dynamic coordination of brain circuits and systems. There are however growing concerns that existing methods for PAC analysis are prone to error and misinterpretation. Improper frequency band selection can render true PAC undetectable, while non-linearities or abrupt changes in the signal can produce spurious PAC. Current methods require large amounts of data and lack formal statistical inference tools. We describe here a novel approach for PAC analysis that substantially addresses these problems. We use a state space model to estimate the component oscillations, avoiding problems with frequency band selection, nonlinearities, and sharp signal transitions. We represent cross-frequency coupling in parametric and time-varying forms to further improve statistical efficiency and estimate the posterior distribution of the coupling parameters to derive their credible intervals. We demonstrate the method using simulated data, rat local field potentials (LFP) data, and human EEG data.P01GM118269 - NIH HHS; R01AG056015 - NIH HHS; R01AG054081 - NIH HHS; R21DA048323 - NIH HHSPublished versio

REM sleep stabilizes hypothalamic representation of feeding behavior

During rapid eye movement (REM) sleep, behavioral unresponsiveness contrasts strongly with intense brain-wide neural network dynamics. Yet, the physiological functions of this cellular activation remain unclear. Using in vivo calcium imaging in freely behaving mice, we found that inhibitory neurons in the lateral hypothalamus (LHvgat) show unique activity patterns during feeding that are reactivated during REM, but not non-REM, sleep. REM sleep-specific optogenetic silencing of LHvgat cells induced a reorganization of these activity patterns during subsequent feeding behaviors accompanied by decreased food intake. Our findings provide evidence for a role for REM sleep in the maintenance of cellular representations of feeding behavior

Neurological prognostication of outcome in patients in coma after cardiac arrest.

Management of coma after cardiac arrest has improved during the past decade, allowing an increasing proportion of patients to survive, thus prognostication has become an integral part of post-resuscitation care. Neurologists are increasingly confronted with raised expectations of next of kin and the necessity to provide early predictions of long-term prognosis. During the past decade, as technology and clinical evidence have evolved, post-cardiac arrest prognostication has moved towards a multimodal paradigm combining clinical examination with additional methods, consisting of electrophysiology, blood biomarkers, and brain imaging, to optimise prognostic accuracy. Prognostication should never be based on a single indicator; although some variables have very low false positive rates for poor outcome, multimodal assessment provides resassurance about the reliability of a prognostic estimate by offering concordant evidence

Spectral discontinuity in concatenative speech synthesis – perception, join costs and feature transformations

This thesis explores the problem of determining an objective measure to represent human perception of spectral discontinuity in concatenative speech synthesis. Such measures are used as join costs to quantify the compatibility of speech units for concatenation in unit selection synthesis. No previous study has reported a spectral measure that satisfactorily correlates with human perception of discontinuity. An analysis of the limitations of existing measures and our understanding of the human auditory system were used to guide the strategies adopted to advance a solution to this problem. A listening experiment was conducted using a database of concatenated speech with results indicating the perceived continuity of each concatenation. The results of this experiment were used to correlate proposed measures of spectral continuity with the perceptual results. A number of standard speech parametrisations and distance measures were tested as measures of spectral continuity and analysed to identify their limitations. Time-frequency resolution was found to limit the performance of standard speech parametrisations.As a solution to this problem, measures of continuity based on the wavelet transform were proposed and tested, as wavelets offer superior time-frequency resolution to standard spectral measures. A further limitation of standard speech parametrisations is that they are typically computed from the magnitude spectrum. However, the auditory system combines information relating to the magnitude spectrum, phase spectrum and spectral dynamics. The potential of phase and spectral dynamics as measures of spectral continuity were investigated. One widely adopted approach to detecting discontinuities is to compute the Euclidean distance between feature vectors about the join in concatenated speech. The detection of an auditory event, such as the detection of a discontinuity, involves processing high up the auditory pathway in the central auditory system. The basic Euclidean distance cannot model such behaviour. A study was conducted to investigate feature transformations with sufficient processing complexity to mimic high level auditory processing. Neural networks and principal component analysis were investigated as feature transformations. Wavelet based measures were found to outperform all measures of continuity based on standard speech parametrisations. Phase and spectral dynamics based measures were found to correlate with human perception of discontinuity in the test database, although neither measure was found to contribute a significant increase in performance when combined with standard measures of continuity. Neural network feature transformations were found to significantly outperform all other measures tested in this study, producing correlations with perceptual results in excess of 90%

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

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

TEMPORAL DATA EXTRACTION AND QUERY SYSTEM FOR EPILEPSY SIGNAL ANALYSIS

The 2016 Epilepsy Innovation Institute (Ei2) community survey reported that unpredictability is the most challenging aspect of seizure management. Effective and precise detection, prediction, and localization of epileptic seizures is a fundamental computational challenge. Utilizing epilepsy data from multiple epilepsy monitoring units can enhance the quantity and diversity of datasets, which can lead to more robust epilepsy data analysis tools. The contributions of this dissertation are two-fold. One is the implementation of a temporal query for epilepsy data; the other is the machine learning approach for seizure detection, seizure prediction, and seizure localization. The three key components of our temporal query interface are: 1) A pipeline for automatically extract European Data Format (EDF) information and epilepsy annotation data from cross-site sources; 2) Data quantity monitoring for Epilepsy temporal data; 3) A web-based annotation query interface for preliminary research and building customized epilepsy datasets. The system extracted and stored about 450,000 epilepsy-related events of more than 2,497 subjects from seven institutes up to September 2019. Leveraging the epilepsy temporal events query system, we developed machine learning models for seizure detection, prediction, and localization. Using 135 extracted features from EEG signals, we trained a channel-based eXtreme Gradient Boosting model to detect seizures on 8-second EEG segments. A long-term EEG recording evaluation shows that the model can detect about 90.34% seizures on an existing EEG dataset with 961 hours of data. The model achieved 89.88% accuracy, 92.32% sensitivity, and 84.76% AUC based on the segments evaluation. We also introduced a transfer learning approach consisting of 1) a base deep learning model pre-trained by ImageNet dataset and 2) customized fully connected layers, to train the patient-specific pre-ictal and inter-ictal data from our database. Two convolutional neural network architectures were evaluated using 53 pre-ictal segments and 265 continuous hours of inter-ictal EEG data. The evaluation shows that our model reached 86.79% sensitivity and 3.38% false-positive rate. Another transfer learning model for seizure localization uses a pre-trained ResNext50 structure and was trained with an image augmentation dataset labeling by fingerprint. Our model achieved 88.22% accuracy, 34.99% sensitivity, 1.02% false-positive rate, and 34.3% positive likelihood rate

Global neural rhythm control by local neuromodulation

Neural oscillations are a ubiquitous form of neural activity seen across scales and modalities. These neural rhythms correlate with diverse cognitive functions and brain states. One mechanism for changing the oscillatory dynamics of large neuronal populations is through neuromodulator activity. An intriguing phenomenon explored here is when local neuromodulation of a distinct neuron type within a single brain nucleus exerts a powerful influence on global cortical rhythms. One approach to investigate the impact of local circuits on global rhythms is through optogenetic techniques. My first project involves the statistical analysis of electrophysiological recordings of an optogenetically-mediated Parkinsonian phenotype. Empirical studies demonstrate that Parkinsonian motor deficits correlate with the emergence of exaggerated beta frequency (15-30 Hz) oscillations throughout the cortico-basal ganglia-thalamic network. However, the mechanism of these aberrant oscillatory dynamics is not well understood. A previous modeling study predicted that cholinergic neuromodulation of medium spiny neurons in the striatum of the basal ganglia may mediate the pathologic beta rhythm. Here, this hypothesis was tested using selective optogenetic stimulation of striatal cholinergic interneurons in normal mice; stimulation robustly and reversibly amplified beta oscillations and Parkinsonian motor symptoms. The modulation of global rhythms by local networks was further studied using computational modeling in the context of intrathalamic neuromodulation. While intrathalamic vasoactive intestinal peptide (VIP) is known to cause long-lasting excitation in vitro, its in vivo dynamical effects have not been reported. Here, biophysical computational models were used to elucidate the impact of VIP on thalamocortical dynamics during sleep and propofol general anesthesia. The modeling results suggest that VIP can form robust sleep spindle oscillations and control aspects of sleep architecture through a novel homeostatic mechanism. This homeostatic mechanism would be inhibited by general anesthesia, representing a new mechanism contributing to anesthetic-induced loss of consciousness. While the previous two projects differed in their use of empirical versus theoretical methods, a challenge common to both domains is the difficulty in visualizing and analyzing large multi-dimensional datasets. A tool to mitigate these issues is introduced here: GIMBL-Vis is a Graphical Interactive Multi-dimensional extensiBLe Visualization toolbox for Matlab. This toolbox simplifies the process of exploring multi-dimensional data in Matlab by providing a graphical interface for visualization and analysis. Furthermore, it provides an extensible open platform for distributed development by the community