Topographical Features of Pediatric Electroencephalography during High Initial Concentration Sevoflurane for Inhalational Induction of Anesthesia.

BACKGROUND: High-density electroencephalographic (EEG) monitoring remains underutilized in clinical anesthesia, despite its obvious utility in unraveling the profound physiologic impact of these agents on central nervous system functioning. In school-aged children, the routine practice of rapid induction with high concentrations of inspiratory sevoflurane is commonplace, given its favorable efficacy and tolerance profile. However, few studies investigate topographic EEG during the critical timepoint coinciding with loss of responsiveness-a key moment for anesthesiologists in their everyday practice. The authors hypothesized that high initial sevoflurane inhalation would better precipitate changes in brain regions due to inhomogeneities in maturation across three different age groups compared with gradual stepwise paradigms utilized by other investigators. Knowledge of these changes may inform strategies for agent titration in everyday clinical settings. METHODS: A total of 37 healthy children aged 5 to 10 yr underwent induction with 4% or greater sevoflurane in high-flow oxygen. Perturbations in anesthetic state were investigated in 23 of these children using 64-channel EEG with the Hjorth Laplacian referencing scheme. Topographical maps illustrated absolute, relative, and total band power across three age groups: 5 to 6 yr (n = 7), 7 to 8 yr (n = 8), and 9 to 10 yr (n = 8). RESULTS: Spectral analysis revealed a large shift in total power driven by increased delta oscillations. Well-described topographic patterns of anesthesia, e.g., frontal predominance, paradoxical beta excitation, and increased slow activity, were evident in the topographic maps. However, there were no statistically significant age-related changes in spectral power observed in a midline electrode subset between the groups when responsiveness was lost compared to the resting state. CONCLUSIONS: High initial concentration sevoflurane induction causes large-scale topographic effects on the pediatric EEG. Within the minute after unresponsiveness, this dosage may perturb EEG activity in children to an extent where age-related differences are not discernible.

Alpha blocking and 1/fß spectral scaling in resting EEG can be accounted for by a sum of damped alpha band oscillatory processes.

The dynamical and physiological basis of alpha band activity and 1/fß noise in the EEG are the subject of continued speculation. Here we conjecture, on the basis of empirical data analysis, that both of these features may be economically accounted for through a single process if the resting EEG is conceived of being the sum of multiple stochastically perturbed alpha band damped linear oscillators with a distribution of dampings (relaxation rates). The modulation of alpha-band and 1/fß noise activity by changes in damping is explored in eyes closed (EC) and eyes open (EO) resting state EEG. We aim to estimate the distribution of dampings by solving an inverse problem applied to EEG power spectra. The characteristics of the damping distribution are examined across subjects, sensors and recording condition (EC/EO). We find that there are robust changes in the damping distribution between EC and EO recording conditions across participants. The estimated damping distributions are found to be predominantly bimodal, with the number and position of the modes related to the sharpness of the alpha resonance and the scaling (ß) of the power spectrum (1/fß). The results suggest that there exists an intimate relationship between resting state alpha activity and 1/fß noise with changes in both governed by changes to the damping of the underlying alpha oscillatory processes. In particular, alpha-blocking is observed to be the result of the most weakly damped distribution mode becoming more heavily damped. The results suggest a novel way of characterizing resting EEG power spectra and provides new insight into the central role that damped alpha-band activity may play in characterising the spatio-temporal features of resting state EEG.

Performance of the bispectral index and electroencephalograph derived parameters of anesthetic depth during emergence from xenon and sevoflurane anesthesia.

Many processed EEG monitors (pEEG) are unreliable when non-GABAergic anesthetic agents are used. The primary aim of the study was to compare the response of the Bispectral Index (BIS) during emergence from anesthesia maintained by xenon and sevoflurane. To better understand the variation in response of pEEG to these agents, we also compared several EEG derived parameters relevant to pEEG monitoring during emergence. Twenty-four participants scheduled for lithotripsy were randomized to receive xenon or sevoflurane anesthesia. Participants were monitored with the BIS and had simultaneous raw EEG collected. BIS index values were compared at three key emergence timepoints: first response, eyes open and removal of airway. Two sets of EEG derived parameters, three related to the BIS: relative beta ratio, SynchFastSlow and SynchFastSlow biocoherence, and two unrelated to the BIS: spectral edge frequency and the composite cortical state, were calculated for comparison. BIS index values were significantly lower in the xenon group than the sevoflurane group at each emergence timepoint. The relative beta ratio parameter increased significantly during emergence in the sevoflurane group but not in the xenon group. The spectral edge frequency and composite cortical state parameters increased significantly in both groups during emergence. The BIS index is lower at equivalent stages of behavioural response during emergence from xenon anesthesia when compared to sevoflurane anesthesia, most likely due to differences in how these two agents influence the relative beta ratio. The spectral edge frequency and composite cortical state might better reflect emergence from xenon anaesthesia.Clinical trial number and registry Australia New Zealand Clinical Trials Registry Number: ACTRN12618000916246.

Inferring a simple mechanism for alpha-blocking by fitting a neural population model to EEG spectra.

Alpha blocking, a phenomenon where the alpha rhythm is reduced by attention to a visual, auditory, tactile or cognitive stimulus, is one of the most prominent features of human electroencephalography (EEG) signals. Here we identify a simple physiological mechanism by which opening of the eyes causes attenuation of the alpha rhythm. We fit a neural population model to EEG spectra from 82 subjects, each showing a different degree of alpha blocking upon opening of their eyes. Though it has been notoriously difficult to estimate parameters by fitting such models, we show how, by regularizing the differences in parameter estimates between eyes-closed and eyes-open states, we can reduce the uncertainties in these differences without significantly compromising fit quality. From this emerges a parsimonious explanation for the spectral differences between states: Changes to just a single parameter, pei, corresponding to the strength of a tonic excitatory input to the inhibitory cortical population, are sufficient to explain the reduction in alpha rhythm upon opening of the eyes. We detect this by comparing the shift in each model parameter between eyes-closed and eyes-open states. Whereas changes in most parameters are weak or negligible and do not scale with the degree of alpha attenuation across subjects, the change in pei increases monotonically with the degree of alpha blocking observed. These results indicate that opening of the eyes reduces alpha activity by increasing external input to the inhibitory cortical population.

Comparison of the Spectral Features of the Frontal Electroencephalogram in Patients Receiving Xenon and Sevoflurane General Anesthesia.

BACKGROUND: Depth-of-anesthesia monitoring is often utilized for patients receiving xenon anesthesia. Processed electroencephalogram (EEG) depth-of-anesthesia monitoring relies to a significant extent on frequency domain analysis of the frontal EEG, and there is evidence that the spectral features observed under anesthesia vary significantly between anesthetic agents. The spectral features of the EEG during xenon anesthesia for a surgical procedure have not previously been described. METHODS: Twenty-four participants scheduled for general anesthesia for lithotripsy were randomized to receive either xenon anesthesia or sevoflurane anesthesia. Frontal EEG recordings were obtained from each participant via the Brain Anesthesia Response Monitor (BARM). Twenty-two EEG recordings were suitable for analysis: 11 in participants who received sevoflurane and 11 in participants who received xenon. Spectrograms for the duration of the anesthetic episode were produced for each participant. Group-level spectral analysis was calculated for two 30-second EEG epochs: one recorded at awake baseline and the other during maintenance anesthesia. A linear mixed-effects model was utilized to compare the changes in 5 frequency bands from baseline to maintenance between the 2 groups. RESULTS: The spectrograms of sevoflurane participants illustrate an increase in frontal delta (0.5-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) band power during maintenance anesthesia. In contrast, spectrograms of the xenon participants did not illustrate an increase in alpha power. The results of the linear mixed-effects model indicate that both agents were associated with a significant increase in delta power from baseline to maintenance. There was no significant difference in the magnitude of this increase observed between the agents. In contrast, sevoflurane anesthesia was associated with significantly greater absolute power in the theta, alpha, and beta (13-30 Hz) bands when compared to xenon. In terms of relative power, xenon was associated with a significant increase in delta power compared to sevoflurane, while sevoflurane was associated with greater increases in relative theta, alpha, and beta power. CONCLUSIONS: Both xenon anesthesia and sevoflurane anesthesia were associated with significant increases in delta power. Sevoflurane anesthesia was also associated with increases in theta, alpha, and beta power, while xenon anesthesia was associated with greater consolidation of power in the delta band. Xenon anesthesia and sevoflurane anesthesia are associated with distinct spectral features. These findings suggest that appropriate depth-of-anesthesia monitoring may require the development of agent-specific spectral measures of unconsciousness.

Evidence that alpha blocking is due to increases in system-level oscillatory damping not neuronal population desynchronisation.

The attenuation of the alpha rhythm following eyes-opening (alpha blocking) is among the most robust features of the human electroencephalogram with the prevailing view being that it is caused by changes in neuronal population synchrony. To further study the basis for this phenomenon we use theoretically motivated fixed-order Auto-Regressive Moving-Average (ARMA) time series modelling to study the oscillatory dynamics of spontaneous alpha-band electroencephalographic activity in eyes-open and eyes-closed conditions and its modulation by the NMDA antagonist ketamine. We find that the reduction in alpha-band power between eyes-closed and eyes-open states is explicable in terms of an increase in the damping of stochastically perturbed alpha-band relaxation oscillatory activity. These changes in damping are putatively modified by the antagonism of NMDA-mediated glutamatergic neurotransmission but are not directly driven by changes in input to cortex nor by reductions in the phase synchronisation of populations of near identical oscillators. These results not only provide a direct challenge to the dominant view of the role that thalamus and neuronal population de-/synchronisation have in the genesis and modulation of alpha electro-/magnetoencephalographic activity but also suggest potentially important physiological determinants underlying its dynamical control and regulation.

Parameter estimation and identifiability in a neural population model for electro-cortical activity.

Electroencephalography (EEG) provides a non-invasive measure of brain electrical activity. Neural population models, where large numbers of interacting neurons are considered collectively as a macroscopic system, have long been used to understand features in EEG signals. By tuning dozens of input parameters describing the excitatory and inhibitory neuron populations, these models can reproduce prominent features of the EEG such as the alpha-rhythm. However, the inverse problem, of directly estimating the parameters from fits to EEG data, remains unsolved. Solving this multi-parameter non-linear fitting problem will potentially provide a real-time method for characterizing average neuronal properties in human subjects. Here we perform unbiased fits of a 22-parameter neural population model to EEG data from 82 individuals, using both particle swarm optimization and Markov chain Monte Carlo sampling. We estimate how much is learned about individual parameters by computing Kullback-Leibler divergences between posterior and prior distributions for each parameter. Results indicate that only a single parameter, that determining the dynamics of inhibitory synaptic activity, is directly identifiable, while other parameters have large, though correlated, uncertainties. We show that the eigenvalues of the Fisher information matrix are roughly uniformly spaced over a log scale, indicating that the model is sloppy, like many of the regulatory network models in systems biology. These eigenvalues indicate that the system can be modeled with a low effective dimensionality, with inhibitory synaptic activity being prominent in driving system behavior.

Interictal and ictal source localization for epilepsy surgery using high-density EEG with MEG: a prospective long-term study.

Drug-resistant focal epilepsy is a major clinical problem and surgery is under-used. Better non-invasive techniques for epileptogenic zone localization are needed when MRI shows no lesion or an extensive lesion. The problem is interictal and ictal localization before propagation from the epileptogenic zone. High-density EEG (HDEEG) and magnetoencephalography (MEG) offer millisecond-order temporal resolution to address this but co-acquisition is challenging, ictal MEG studies are rare, long-term prospective studies are lacking, and fundamental questions remain. Should HDEEG-MEG discharges be assessed independently [electroencephalographic source localization (ESL), magnetoencephalographic source localization (MSL)] or combined (EMSL) for source localization? Which phase of the discharge best characterizes the epileptogenic zone (defined by intracranial EEG and surgical resection relative to outcome)? Does this differ for interictal and ictal discharges? Does MEG detect mesial temporal lobe discharges? Thirteen patients (10 non-lesional, three extensive-lesional) underwent synchronized HDEEG-MEG (72-94 channel EEG, 306-sensor MEG). Source localization (standardized low-resolution tomographic analysis with MRI patient-individualized boundary-element method) was applied to averaged interictal epileptiform discharges (IED) and ictal discharges at three phases: 'early-phase' (first latency 90% explained variance), 'mid-phase' (first of 50% rising-phase, 50% mean global field power), 'late-phase' (negative peak). 'Earliest-solution' was the first of the three early-phase solutions (ESL, MSL, EMSL). Prospective follow-up was 3-21 (median 12) months before surgery, 14-39 (median 21) months after surgery. IEDs (n = 1474) were recorded, seen in: HDEEG only, 626 (42%); MEG only, 232 (16%); and both 616 (42%). Thirty-three seizures were captured, seen in: HDEEG only, seven (21%); MEG only, one (3%); and both 25 (76%). Intracranial EEG was done in nine patients. Engel scores were I (9/13, 69%), II (2/13,15%), and III (2/13). MEG detected baso-mesial temporal lobe epileptogenic zone sources. Epileptogenic zone OR [odds ratio(s)] were significantly higher for earliest-solution versus early-phase IED-surgical resection and earliest-solution versus all mid-phase and late-phase solutions. ESL outperformed EMSL for ictal-surgical resection [OR 3.54, 95% confidence interval (CI) 1.09-11.55, P = 0.036]. MSL outperformed EMSL for IED-intracranial EEG (OR 4.67, 95% CI 1.19-18.34, P = 0.027). ESL outperformed MSL for ictal-surgical resection (OR 3.73, 95% CI 1.16-12.03, P = 0.028) but was outperformed by MSL for IED-intracranial EEG (OR 0.18, 95% CI 0.05-0.73, P = 0.017). Thus, (i) HDEEG and MEG source solutions more accurately localize the epileptogenic zone at the earliest resolvable phase of interictal and ictal discharges, not mid-phase (as is common practice) or late peak-phase (when signal-to-noise ratios are maximal); (ii) from empirical observation of the differential timing of HDEEG and MEG discharges and based on the superiority of ESL plus MSL over either modality alone and over EMSL, concurrent HDEEG-MEG signals should be assessed independently, not combined; (iii) baso-mesial temporal lobe sources are detectable by MEG; and (iv) MEG is not 'more accurate' than HDEEG-emphasis is best placed on the earliest signal (whether HDEEG or MEG) amenable to source localization. Our findings challenge current practice and our reliance on invasive monitoring in these patients. 10.1093/brain/awz015_video1 awz015media1 6018582479001.

Epilepsyecosystem.org: crowd-sourcing reproducible seizure prediction with long-term human intracranial EEG.

Accurate seizure prediction will transform epilepsy management by offering warnings to patients or triggering interventions. However, state-of-the-art algorithm design relies on accessing adequate long-term data. Crowd-sourcing ecosystems leverage quality data to enable cost-effective, rapid development of predictive algorithms. A crowd-sourcing ecosystem for seizure prediction is presented involving an international competition, a follow-up held-out data evaluation, and an online platform, Epilepsyecosystem.org, for yielding further improvements in prediction performance. Crowd-sourced algorithms were obtained via the 'Melbourne-University AES-MathWorks-NIH Seizure Prediction Challenge' conducted at kaggle.com. Long-term continuous intracranial electroencephalography (iEEG) data (442 days of recordings and 211 lead seizures per patient) from prediction-resistant patients who had the lowest seizure prediction performances from the NeuroVista Seizure Advisory System clinical trial were analysed. Contestants (646 individuals in 478 teams) from around the world developed algorithms to distinguish between 10-min inter-seizure versus pre-seizure data clips. Over 10 000 algorithms were submitted. The top algorithms as determined by using the contest data were evaluated on a much larger held-out dataset. The data and top algorithms are available online for further investigation and development. The top performing contest entry scored 0.81 area under the classification curve. The performance reduced by only 6.7% on held-out data. Many other teams also showed high prediction reproducibility. Pseudo-prospective evaluation demonstrated that many algorithms, when used alone or weighted by circadian information, performed better than the benchmarks, including an average increase in sensitivity of 1.9 times the original clinical trial sensitivity for matched time in warning. These results indicate that clinically-relevant seizure prediction is possible in a wider range of patients than previously thought possible. Moreover, different algorithms performed best for different patients, supporting the use of patient-specific algorithms and long-term monitoring. The crowd-sourcing ecosystem for seizure prediction will enable further worldwide community study of the data to yield greater improvements in prediction performance by way of competition, collaboration and synergism.10.1093/brain/awy210_video1awy210media15817489051001.

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

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.

Neural mass model-based tracking of anesthetic brain states.

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.

Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled Propofol-Remifentanil Anesthesia.

BACKGROUND: Current electroencephalogram (EEG)-derived measures provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. Recently, the neurophysiologically based EEG measures of cortical input (CI) and cortical state (CS) have been shown to be prospective indicators of analgesia/antinociception and hypnosis, respectively. In this study, we compared CI and an alternate measure of CS, the composite cortical state (CCS), with the Bispectral Index (BIS) and another recently developed measure of antinociception, the composite variability index (CVI). CVI is an EEG-derived measure based on a weighted combination of BIS and estimated electromyographic activity. By assessing the relationship between these indices for equivalent levels of hypnosis (as quantified using the BIS) and the nociceptive-antinociceptive balance (as determined by the predicted effect-site concentration of remifentanil), we sought to evaluate whether combining hypnotic and analgesic measures could better predict movement in response to a noxious stimulus than when used alone. METHODS: Time series of BIS and CVI indices and the raw EEG from a previously published study were reanalyzed. In our current study, the data from 80 patients, each randomly allocated to a target hypnotic level (BIS 50 or BIS 70) and a target remifentanil level (Remi-0, -2, -4 or -6 ng/mL), were included in the analysis. CCS, CI, BIS, and CVI were calculated or quantified at baseline and at a number of intervals after the application of the Observer's Assessment of Alertness/Sedation scale and a subsequent tetanic stimulus. The dependency of the putative measures of antinociception CI and CVI on effect-site concentration of remifentanil was then quantified, together with their relationship to the hypnotic measures CCS and BIS. Finally, statistical clustering methods were used to evaluate the extent to which simple combinations of antinociceptive and hypnotic measures could better detect and predict response to stimulation. RESULTS: Before stimulation, both CI and CVI differentiated patients who received remifentanil from those who were randomly allocated to the Remi-0 group (CI: Cohen's d = 0.65, 95% confidence interval, 0.48-0.83; CVI: Cohen's d = 0.72, 95% confidence interval, 0.56-0.88). Strong correlations between BIS and CCS were found (at different periods: 0.55 < R2 < 0.68, P < 0.001). Application of the Observer's Assessment of Alertness/Sedation stimulus was associated with changes in CI and CCS, whereas, subsequent to the application of both stimuli, changes in all measures were seen. Pairwise combinations of CI and CCS showed higher sensitivity in detecting response to stimulation than CVI and BIS combined (sensitivity [99% confidence interval], 75.8% [52.7%-98.8%] vs 42% [15.4%-68.5%], P = 0.006), with specificity for CI and CCS approaching significance (52% [34.7%-69.3%] vs 24% [9.1%-38.9%], P = 0.0159). CONCLUSIONS: Combining electroencephalographically derived hypnotic and analgesic quantifiers may enable better prediction of patients who are likely to respond to tetanic stimulation.

Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 µg/kg (fentanyl low dose, FLD) or 24 µg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

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

BACKGROUND: 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. METHODS: Children aged 5 to 15 yr had multichannel electroencephalographic recordings during induction and emergence from anesthesia during minor surgical procedures. Of these, five children displayed ED after sevoflurane anesthesia. Measures of cortical functional connectivity previously used to evaluate anesthetic action in adults were compared between ED and age-, sex-, and anesthetic-matched non-ED children during emergence from anesthesia. RESULTS: At the termination of sevoflurane anesthesia, the electroencephalogram in both ED and control patients showed delta frequency slowing and frontally dominant alpha activity, followed by a prolonged state with low-voltage, fast frequency activity (referred to as an indeterminate state). In children with ED, arousal with delirious behavior and a variety of electroencephalogram patterns occurred during the indeterminate state, before the appearance of normal wake or sleep patterns. The electroencephalogram in children without ED progressed from the indeterminate state to classifiable sleep or drowsy states, before peaceful awakening. Statistically significant differences in frontal lobe functional connectivity were identified between children with ED and non-ED. CONCLUSIONS: ED is associated with arousal from an indeterminate state before the onset of sleep-like electroencephalogram patterns. Increased frontal lobe cortical functional connectivity observed in ED, immediately after the termination of sevoflurane anesthesia, will have important implications for the development of methods to predict ED, the design of preventative strategies, and efforts to better understand its pathophysiology.

Four dimensional chaos and intermittency in a mesoscopic model of the electroencephalogram.

The occurrence of so-called four dimensional chaos in dynamical systems represented by coupled, nonlinear, ordinary differential equations is rarely reported in the literature. In this paper, we present evidence that Liley's mesoscopic theory of the electroencephalogram (EEG), which has been used to describe brain activity in a variety of clinically relevant contexts, possesses a chaotic attractor with a Kaplan-Yorke dimension significantly larger than three. This accounts for simple, high order chaos for a physiologically admissible parameter set. Whilst the Lyapunov spectrum of the attractor has only one positive exponent, the contracting dimensions are such that the integer part of the Kaplan-Yorke dimension is three, thus giving rise to four dimensional chaos. A one-parameter bifurcation analysis with respect to the parameter corresponding to extracortical input is conducted, with results indicating that the origin of chaos is due to an inverse period doubling cascade. Hence, in the vicinity of the high order, strange attractor, the model is shown to display intermittent behavior, with random alternations between oscillatory and chaotic regimes. This phenomenon represents a possible dynamical justification of some of the typical features of clinically established EEG traces, which can arise in the case of burst suppression in anesthesia and epileptic encephalopathies in early infancy.

Axonal velocity distributions in neural field equations.

By modelling the average activity of large neuronal populations, continuum mean field models (MFMs) have become an increasingly important theoretical tool for understanding the emergent activity of cortical tissue. In order to be computationally tractable, long-range propagation of activity in MFMs is often approximated with partial differential equations (PDEs). However, PDE approximations in current use correspond to underlying axonal velocity distributions incompatible with experimental measurements. In order to rectify this deficiency, we here introduce novel propagation PDEs that give rise to smooth unimodal distributions of axonal conduction velocities. We also argue that velocities estimated from fibre diameters in slice and from latency measurements, respectively, relate quite differently to such distributions, a significant point for any phenomenological description. Our PDEs are then successfully fit to fibre diameter data from human corpus callosum and rat subcortical white matter. This allows for the first time to simulate long-range conduction in the mammalian brain with realistic, convenient PDEs. Furthermore, the obtained results suggest that the propagation of activity in rat and human differs significantly beyond mere scaling. The dynamical consequences of our new formulation are investigated in the context of a well known neural field model. On the basis of Turing instability analyses, we conclude that pattern formation is more easily initiated using our more realistic propagator. By increasing characteristic conduction velocities, a smooth transition can occur from self-sustaining bulk oscillations to travelling waves of various wavelengths, which may influence axonal growth during development. Our analytic results are also corroborated numerically using simulations on a large spatial grid. Thus we provide here a comprehensive analysis of empirically constrained activity propagation in the context of MFMs, which will allow more realistic studies of mammalian brain activity in the future.

Nitrous oxide paradoxically modulates slow electroencephalogram oscillations: implications for anesthesia monitoring.

BACKGROUND: Nitrous oxide (N(2)O) is one of the oldest analgesics/adjuvant agents still in use today; however, its effects on the human electroencephalogram (EEG) remain unclear. It has been proposed that N(2)O may enhance higher-frequency EEG activity (often indicative of alert states and cognition) duration sedation. This possibly paradoxical effect has been used to explain the failure of many EEG monitors to capture the effects of N(2)O on patient state during anesthesia. To better understand the poor efficacy of current EEG approaches to monitoring N(2)O action, we quantitatively studied the sole effect of N(2)O on the resting EEG in healthy volunteers using multichannel EEG recordings under noise-minimized laboratory conditions. METHODS: Healthy male volunteers were administered 20% (n = 10), 40% (n = 10), or 60% (n = 5) inspired N(2)O mixed with oxygen during noise-shielded EEG recordings. N(2)O was administered over a 20-minute period involving a 5-minute equilibration period and 5-minute washout. EEG spectral edge frequency (95%), median power frequency, total power, and band-limited power (δ, , α, ß, and γ) were used as quantitative EEG parameters. The changes in these EEG parameters were quantified throughout N(2)O inhalation and compared between predrug baseline, peak drug effect, and washout. RESULTS: Quantification of changes in spectral power during N(2)O inhalation showed only minor changes in estimates of spectral edge and median power frequency, whereas significant reductions in total power were observed at frontal sites during peak gas effect (P = 0.001; mean reduction [95% confidence interval]: 41.90 µV(2) [18.19-65.61 µV(2)]) that rebounded during N(2)O washout. Such changes in total power were driven by shifts in low-frequency power (δ/), which were most elevated at frontal sites. CONCLUSION: Rather than directly enhancing high-frequency EEG power (ß or γ bands), N(2)O seems to preserve the awake features of resting EEG (α band) and suppress power in those bands in which increases are typically associated with sedation/hypnosis (δ and ). These data suggest that N(2)O's suppression of low-frequency EEG power may help to explain previously reported difficulties in attempting to monitor patient state with the EEG during anesthesia involving N(2)O. Because increases in low-frequency power typically indicate increasing anesthesia, N(2)O's suppression of such activity and its rebound during washout would paradoxically influence EEG monitoring parameters. Therefore, correcting for such effects is expected to improve future monitoring methods.

Interictal spike localization for epilepsy surgery using magnetoencephalography beamforming.

OBJECTIVE: Magnetoencephalography (MEG) kurtosis beamforming is an automated localization method for focal epilepsy. Visual examination of virtual sensors, which are source activities reconstructed by beamforming, can improve performance but can be time-consuming for neurophysiologists. We propose a framework to automate the method and evaluate its effectiveness against surgical resections and outcomes. METHODS: We retrospectively analyzed MEG recordings of 13 epilepsy surgery patients who had one-year minimum post-operative follow-up. Kurtosis beamforming was applied and manual inspection was confined to morphological clusters. The region with the Maximum Interictal Spike Frequency (MISF) was validated against prospectively modelled sLORETA solutions and surgical resections linked to outcome. RESULTS: Our approach localized spikes in 12 out of 13 patients. In eight patients with Engel I surgical outcomes, beamforming MISF regions were concordant with surgical resection at overlap level for five patients and at lobar level for three patients. The MISF regions localized to spike onset and propagation modelled by sLORETA in two and six patients, respectively. CONCLUSIONS: Automated beamforming using MEG can predict postoperative seizure freedom at the lobar level but tends to localize propagated MEG spikes. SIGNIFICANCE: MEG beamforming may contribute to non-invasive procedures to predict surgical outcome for patients with drug-refractory focal epilepsy.

Propofol and remifentanil differentially modulate frontal electroencephalographic activity.

BACKGROUND: The purpose of this study was to evaluate a new, physiologically inspired method for the analysis of the electroencephalogram during propofol-remifentanil anesthesia. Based on fixed-order autoregressive moving-average modeling, this method was hypothesized to be capable of dissociating the effects that hypnotic and analgesic agents have on brain electrical activity. METHODS: Raw electroencephalographic waves from a previously published study were reanalyzed. In this study, 45 American Society of Anesthesiologists status I patients were randomly allocated to one of three groups according to a specific target effect-site remifentanil concentration (0, 2, and 4 ng/ml). All patients received stepwise-increased targeted effect-site concentrations of propofol (CePROP). At each step change in target CePROP, the Observer's Assessment of Alertness/Sedation score was evaluated. Raw electroencephalograph was continuously acquired from frontal electrodes. Electroencephalography traces were analyzed using a fixed-order autoregressive moving average model to give derived measures of Cortical State and Cortical Input. Response surfaces were visualized and modeled using Hierarchical Linear Modeling. RESULTS: Cortical State (a measure of cortical responsiveness) and Cortical Input (a measure of the magnitude of cortical input) were shown to respond differently to CePROP and effect-site remifentanil concentration. Cortical Input decreased significantly with increasing effect-site remifentanil concentration, whereas Cortical State remained unchanged with increasing effect-site remifentanil concentration but decreased with increasing CePROP. CONCLUSION: Because Cortical State responds principally to variations in CePROP, it is a potential measure of hypnosis, whereas the dependence of Cortical Input on effect-site remifentanil concentration suggests that it may be useful as a measure of analgesic efficacy and the nociceptive-antinociceptive balance.

Dissociating the effects of nitrous oxide on brain electrical activity using fixed order time series modeling.

A number of commonly used anesthetics, including nitrous oxide (N2O), are poorly detected by current electroencephalography (EEG)-based measures of anesthetic depth such as the bispectral index. Based on a previously elaborated theory of electrocortical rhythmogenesis we developed a physiologically inspired method of EEG analysis that was hypothesized to be more sensitive in detecting and characterizing N2O effect than the bispectral index, through its combined EEG estimates of cortical input and cortical state. By evaluating sevoflurane-induced loss of consciousness in the presence of low brain concentrations of N2O in 38 elective surgical patients, N2O was associated with a statistically significant reduction in the input the frontal cortex received from other cortical and subcortical areas. In contrast the bispectral index responded only to low, but not to high, concentrations of N2O.