Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in Geriatric Patients Under Anesthesia?

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring

Important Issues in Coma and Neuromonitoring

Coma is defined as a state of unconsciousness and lack of response to noxious stimuli. The physiopathology of consciousness and coma is not entirely understood. On the other hand, clinical examination does not give us enough information in all types of coma states. In this chapter, some types of coma and their definition, the necessity of coma monitoring and what we can use for coma monitoring in ICU, algorithms for EEG monitoring, BIS, AppEntropy, permutation entropy and auditory evoked potentials are described. Burst suppression state new theories and cortical connectivity and reactivity during coma as a tool for coma prognosis will be on focus

The (un)conscious mouse as a model for human brain functions: key principles of anesthesia and their impact on translational neuroimaging

In recent years, technical and procedural advances have brought functional magnetic resonance imaging (fMRI) to the field of murine neuroscience. Due to its unique capacity to measure functional activity non-invasively, across the entire brain, fMRI allows for the direct comparison of large-scale murine and human brain functions. This opens an avenue for bidirectional translational strategies to address fundamental questions ranging from neurological disorders to the nature of consciousness. The key challenges of murine fMRI are: (1) to generate and maintain functional brain states that approximate those of calm and relaxed human volunteers, while (2) preserving neurovascular coupling and physiological baseline conditions. Low-dose anesthetic protocols are commonly applied in murine functional brain studies to prevent stress and facilitate a calm and relaxed condition among animals. Yet, current mono-anesthesia has been shown to impair neural transmission and hemodynamic integrity. By linking the current state of murine electrophysiology, Ca(2+) imaging and fMRI of anesthetic effects to findings from human studies, this systematic review proposes general principles to design, apply and monitor anesthetic protocols in a more sophisticated way. The further development of balanced multimodal anesthesia, combining two or more drugs with complementary modes of action helps to shape and maintain specific brain states and relevant aspects of murine physiology. Functional connectivity and its dynamic repertoire as assessed by fMRI can be used to make inferences about cortical states and provide additional information about whole-brain functional dynamics. Based on this, a simple and comprehensive functional neurosignature pattern can be determined for use in defining brain states and anesthetic depth in rest and in response to stimuli. Such a signature can be evaluated and shared between labs to indicate the brain state of a mouse during experiments, an important step toward translating findings across species

Prediction of Nociceptive Responses during Sedation by Linear and Non-Linear Measures of EEG Signals in High Frequencies

The level of sedation in patients undergoing medical procedures evolves continuously, affected by the interaction between the effect of the anesthetic and analgesic agents and the pain stimuli. The monitors of depth of anesthesia, based on the analysis of the electroencephalogram (EEG), have been progressively introduced into the daily practice to provide additional information about the state of the patient. However, the quantification of analgesia still remains an open problem. The purpose of this work is to improve the prediction of nociceptive responses with linear and non-linear measures calculated from EEG signal filtered in frequency bands higher than the traditional bands. Power spectral density and auto-mutual information function was applied in order to predict the presence or absence of the nociceptive responses to different stimuli during sedation in endoscopy procedure. The proposed measures exhibit better performances than the bispectral index (BIS). Values of prediction probability of Pk above 0.75 and percentages of sensitivity and specificity above 70% were achieved combining EEG measures from the traditional frequency bands and higher frequency bands

Population based models of cortical drug response: insights from anaesthesia

A great explanatory gap lies between the molecular pharmacology of psychoactive agents and the neurophysiological changes they induce, as recorded by neuroimaging modalities. Causally relating the cellular actions of psychoactive compounds to their influence on population activity is experimentally challenging. Recent developments in the dynamical modelling of neural tissue have attempted to span this explanatory gap between microscopic targets and their macroscopic neurophysiological effects via a range of biologically plausible dynamical models of cortical tissue. Such theoretical models allow exploration of neural dynamics, in particular their modification by drug action. The ability to theoretically bridge scales is due to a biologically plausible averaging of cortical tissue properties. In the resulting macroscopic neural field, individual neurons need not be explicitly represented (as in neural networks). The following paper aims to provide a non-technical introduction to the mean field population modelling of drug action and its recent successes in modelling anaesthesia

Permutation entropy and its main biomedical and econophysics applications: a review

Entropy is a powerful tool for the analysis of time series, as it allows describing the probability distributions of the possible state of a system, and therefore the information encoded in it. Nevertheless, important information may be codified also in the temporal dynamics, an aspect which is not usually taken into account. The idea of calculating entropy based on permutation patterns (that is, permutations defined by the order relations among values of a time series) has received a lot of attention in the last years, especially for the understanding of complex and chaotic systems. Permutation entropy directly accounts for the temporal information contained in the time series; furthermore, it has the quality of simplicity, robustness and very low computational cost. To celebrate the tenth anniversary of the original work, here we analyze the theoretical foundations of the permutation entropy, as well as the main recent applications to the analysis of economical markets and to the understanding of biomedical systems.Facultad de Ingenierí

A Novel Spike-Wave Discharge Detection Framework Based on the Morphological Characteristics of Brain Electrical Activity Phase Space in an Animal Model

Background: Animal models of absence epilepsy are widely used in childhood absence epilepsy studies. Absence seizures appear in the brain’s electrical activity as a specific spike wave discharge (SWD) pattern. Reviewing long-term brain electrical activity is time-consuming and automatic methods are necessary. On the other hand, nonlinear techniques such as phase space are effective in brain electrical activity analysis. In this study, we present a novel SWD-detection framework based on the geometrical characteristics of the phase space.Methods: The method consists of the following steps: (1) Rat stereotaxic surgery and cortical electrode implantation, (2) Long-term brain electrical activity recording, (3) Phase space reconstruction, (4) Extracting geometrical features such as volume, occupied space, and curvature of brain signal trajectories, and (5) Detecting SDWs based on the thresholding method. We evaluated the approach with the accuracy of the SWDs detection method.Results: It has been demonstrated that the features change significantly in transition from a normal state to epileptic seizures. The proposed approach detected SWDs with 98% accuracy.Conclusion: The result supports that nonlinear approaches can identify the dynamics of brain electrical activity signals

Functional integration in the cortical neuronal network of conscious and anesthetized animals

General anesthesia consists of amnesia, analgesia, areflexia and unconsciousness. How anesthetics suppress consciousness has been a mystery for more than one and a half centuries. The overall goal of my research has been to determine the neural correlates of anesthetic-induced loss of consciousness. I hypothesized that anesthetics induce unconsciousness by interfering with the functional connectivity of neuronal networks of the brain and consequently, reducing the brain\u27s capacity for information processing. To test this hypothesis, I performed experiments in which neuronal spiking activity was measured with chronically implanted microelectrode arrays in the visual cortex of freely-moving rats during wakefulness and at graded levels of anesthesia produced by the inhalational anesthetic agent desflurane. I then applied linear and non-parametric information-theoretic analyses to quantify the concentration-dependent effect of general anesthetics on spontaneous and visually evoked spike firing activity in rat primary visual cortex. Results suggest that desflurane anesthesia disrupts cortical neuronal integration as measured by monosynaptic connectivity, spike burst coherence and information capacity. This research furthers our understanding of the mechanisms involved with the anesthetic-induced LOC which may facilitate in the development of better anesthetic monitoring devices and the creation of effective anesthetic agents that will be free of unwanted side effects

Hybrid head cap for mouse brain studies

Abstract. In this thesis, I present a hybrid head cap in combination with non-invasive multi-channel Electroencephalogram (EEG) and Near-Infrared Spectroscopy (NIRS) to measure brainwaves on mice’s scalps. Laboratory animal research provides insights into multiple potential applications involving humans and other animals. An experimental framework that targets laboratory animals can lead to useful transnational research if it strongly reflects the actual application environment. The non-invasive head cap with three electrodes for EEG and two optodes for NIRS is suggested to measure brainwaves throughout the laboratory mice’s entire brain region without surgical procedures. The suggested hybrid head cap aims to ensure stability in vivo monitoring for mouse brain in a non-invasive way, similarly as the monitoring is performed for the human brain. The experimental part of the work to study the quality of the gathered EEG and fNIRS signals, and usability validation of the head cap, however, was not completed in the planned time frame of the thesis work