recording-brain-electromagnetic-activity-during-administration

Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most ...

Swinburne University of Technology

Parietal networks are hypothesised to play a central role in the cortical information synthesis that supports conscious experience and behavior. Significant reductions in parietal level functional connectivity have been shown to occur during general anesthesia with propofol and a range of other GABAergic general anesthetic agents. Using two analysis approaches (1) a graph theoretic analysis based on surrogate-corrected zero-lag correlations of scalp EEG, and (2) a global coherence analysis based on the EEG cross-spectrum, we reveal that sedation with the NMDA receptor antagonist nitrous oxide (N2O), an agent that has quite different electroencephalographic effects compared to the inductive general anesthetics, also causes significant alterations in parietal level functional networks, as well as changes in full brain and frontal level networks. A total of 20 subjects underwent N2O inhalation at either 20%, 40% or 60% peak N2O/O2 gas concentration levels. N2O-induced reductions in parietal network level functional connectivity (on the order of 50%) were exclusively detected by utilising a surface Laplacian derivation, suggesting that superficial, smaller spatial scale, cortical networks were most affected. In contrast reductions in frontal network functional connectivity were optimally discriminated using a common-reference derivation (reductions on the order of 10%), indicating that the NMDA antagonist N2O induces spatially coherent and widespread perturbations in frontal activity. Our findings not only give important weight to the idea of agent invariant final network changes underlying drug-induced reductions in consciousness, but also provide significant impetus for the application and development of multiscale functional analyses to systematically characterise the network level cortical effects of NMDA receptor related hypofunction. Future work at the source space level will be needed to verify the consistency between cortical network changes seen at the source level and those presented here at the EEG sensor space level.

Modulation of functional EEG networks by the NMDA antagonist nitrous oxide.

This study aimed to characterize the electroencephalogram in children who emerged with emergence delirium (ED) compared with children without ED using methods that involved the assessment of cortical functional connectivity.

Alterations in the functional connectivity of frontal lobe networks preceding emergence delirium in children.

Over the past three decades, a number of seizure prediction, or forecasting, methods have been developed. Although major achievements were accomplished regarding the statistical evaluation of proposed algorithms, it is recognized that further progress is still necessary for clinical application in patients. The lack of physiological motivation can partly explain this limitation. Therefore, a natural question is raised: can computational models of epilepsy be used to improve these methods? Here, we review the literature on the multiple-scale neural modeling of epilepsy and the use of such models to infer physiologic changes underlying epilepsy and epileptic seizures. The authors argue how these methods can be applied to advance the state-of-the-art in seizure forecasting.

Role of multiple-scale modeling of epilepsy in seizure forecasting.

Neural mass model-based tracking of brain states from electroencephalographic signals holds the promise of simultaneously tracking brain states while inferring underlying physiological changes in various neuroscientific and clinical applications. Here, neural mass model-based tracking of brain states using the unscented Kalman filter applied to estimate parameters of the Jansen-Rit cortical population model is evaluated through the application of propofol-based anesthetic state monitoring. In particular, 15 subjects underwent propofol anesthesia induction from awake to anesthetised while behavioral responsiveness was monitored and frontal electroencephalographic signals were recorded. The unscented Kalman filter Jansen-Rit model approach applied to frontal electroencephalography achieved reasonable testing performance for classification of the anesthetic brain state (sensitivity: 0.51; chance sensitivity: 0.17; nearest neighbor sensitivity 0.75) when compared to approaches based on linear (autoregressive moving average) modeling (sensitivity 0.58; nearest neighbor sensitivity: 0.91) and a high performing standard depth of anesthesia monitoring measure, Higuchi Fractal Dimension (sensitivity: 0.50; nearest neighbor sensitivity: 0.88). Moreover, it was found that the unscented Kalman filter based parameter estimates of the inhibitory postsynaptic potential amplitude varied in the physiologically expected direction with increases in propofol concentration, while the estimates of the inhibitory postsynaptic potential rate constant did not. These results combined with analysis of monotonicity of parameter estimates, error analysis of parameter estimates, and observability analysis of the Jansen-Rit model, along with considerations of extensions of the Jansen-Rit model, suggests that the Jansen-Rit model combined with unscented Kalman filtering provides a valuable reference point for future real-time brain state tracking studies. This is especially true for studies of more complex, but still computationally efficient, neural models of anesthesia that can more accurately track the anesthetic brain state, while simultaneously inferring underlying physiological changes that can potentially provide useful clinical information.

Neural mass model-based tracking of anesthetic brain states.

The expansion of frontiers in neural engineering is dependent on the ability to track, detect and predict dynamics in neural tissue. Recent innovations to elucidate information from electrical recordings of brain dynamics, such as epileptic seizure prediction, have involved switching to an active probing paradigm using electrically evoked recordings rather than traditional passive measurements. This paper positions the advantage of probing in terms of information extraction, by using a coupled oscillator Kuramoto model to represent brain dynamics. While active probing performs better at observing underlying system synchrony in Kuramoto networks, especially in non-Gaussian measurement environments, the benefits diminish with increasing relative size of electrode spatial resolution compared to synchrony area. This suggests probing will be useful for improved characterization of synchrony for suitably dense electrode recordings.

Probing to Observe Neural Dynamics Investigated with Networked Kuramoto Oscillators.

Introduction.

Existing electroencephalography (EEG) based depth of anesthesia monitors cannot reliably track sedative or anesthetic states during n-methyl-D-aspartate (NMDA) receptor antagonist based anesthesia with ketamine or nitrous oxide (N2O). Here, a physiologically-motivated depth of anesthesia monitoring algorithm based on autoregressive-moving-average (ARMA) modeling and derivative measures of interest, Cortical State (CS) and Cortical Input (CI), is retrospectively applied in an exploratory manner to the NMDA receptor antagonist N2O, an adjuvant anesthetic gas used in clinical practice. Composite Cortical State (CCS) and Composite Cortical State distance (CCSd), two new modifications of CS, along with CS and CI were evaluated on electroencephalographic (EEG) data of healthy control individuals undergoing N2O inhalation up to equilibrated peak gas concentrations of 20, 40 or 60% N2O/O2. In particular, CCSd has been devised to vary consistently for increasing levels of anesthetic concentration independent of the anesthetic's microscopic mode of action for both N2O and propofol. The strongest effects were observed for the 60% peak gas concentration group. For the 50-60% peak gas levels, individuals showed statistically significant reductions in responsiveness compared to rest, and across the group CS and CCS increased by 39 and 42%, respectively, while CCSd was found to decrease by 398%. On the other hand a clear conclusion regarding the changes in CI could not be reached. These results indicate that, contrary to previous depth of anesthesia monitoring measures, the CS, CCS, and especially CCSd measures derived from frontal EEG are potentially useful for differentiating gas concentration and responsiveness levels in people under N2O. On the other hand, determining the utility of CI in this regard will require larger sample sizes and potentially higher gas concentrations. Future work will assess the sensitivity of CS-based and CI measures to other anesthetics and their utility in a clinical environment.

Assessing nitrous oxide effect using electroencephalographically-based depth of anesthesia measures cortical state and cortical input.

It is now established that epilepsy is characterized by periodic dynamics that increase seizure likelihood at certain times of day, and which are highly patient-specific. However, these dynamics are not typically incorporated into seizure prediction algorithms due to the difficulty of estimating patient-specific rhythms from relatively short-term or unreliable data sources. This work outlines a novel framework to develop and assess seizure forecasts, and demonstrates that the predictive power of forecasting models is improved by circadian information. The analyses used long-term, continuous electrocorticography from nine subjects, recorded for an average of 320 days each. We used a large amount of out-of-sample data (a total of 900 days for algorithm training, and 2879 days for testing), enabling the most extensive post hoc investigation into seizure forecasting. We compared the results of an electrocorticography-based logistic regression model, a circadian probability, and a combined electrocorticography and circadian model. For all subjects, clinically relevant seizure prediction results were significant, and the addition of circadian information (combined model) maximized performance across a range of outcome measures. These results represent a proof-of-concept for implementing a circadian forecasting framework, and provide insight into new approaches for improving seizure prediction algorithms. The circadian framework adds very little computational complexity to existing prediction algorithms, and can be implemented using current-generation implant devices, or even non-invasively via surface electrodes using a wearable application. The ability to improve seizure prediction algorithms through straightforward, patient-specific modifications provides promise for increased quality of life and improved safety for patients with epilepsy.

Article	Year
Modulation of functional EEG networks by the NMDA antagonist nitrous oxide. PloS one\| PubMed ID: 23457568	2013
Alterations in the functional connectivity of frontal lobe networks preceding emergence delirium in children. Anesthesiology\| PubMed ID: 25057840	2014
Role of multiple-scale modeling of epilepsy in seizure forecasting. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society\| PubMed ID: 26035674	2015
Neural mass model-based tracking of anesthetic brain states. NeuroImage\| PubMed ID: 27018048	2016
Probing to Observe Neural Dynamics Investigated with Networked Kuramoto Oscillators. International journal of neural systems\| PubMed ID: 27596927	2017
Introduction. International journal of neural systems\| PubMed ID: 27776439	2017
Assessing nitrous oxide effect using electroencephalographically-based depth of anesthesia measures cortical state and cortical input. Journal of clinical monitoring and computing\| PubMed ID: 28097611	2018
The circadian profile of epilepsy improves seizure forecasting. Brain : a journal of neurology\| PubMed ID: 28899023	2017

Levin Kuhlmann

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