State-related Electroencephalography Microstate Complexity during Propofol- and Esketamine-induced Unconsciousness.

BACKGROUND: Identifying the state-related "neural correlates of consciousness" for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine). METHODS: The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia. RESULTS: The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001). CONCLUSIONS: Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.

Changes in information integration and brain networks during propofol-, dexmedetomidine-, and ketamine-induced unresponsiveness.

BACKGROUND: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. METHODS: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. RESULTS: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05). CONCLUSIONS: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science.

Age-dependent cross frequency coupling features from children to adults during general anesthesia.

BACKGROUND: The frequency coupling characteristics in electroencephalogram (EEG) induced by anesthetics have been well studied in adults, but the investigation of the age-dependent cross frequency coupling features from children to adults is still lacking. METHODS: We analyzed EEG signals recorded from pediatric to adult patients (n = 131), separated into six age groups: <1 year (n = 15), 1-3 years (n = 23), 3-6 years (n = 19), 6-12 years (n = 18), 12-18 years (n = 16), and 18-45 years (n = 40). Age related EEG power and cross frequency coupling analysis (phase amplitude coupling (PAC) and quadratic phase coupling) of data from maintenance of a surgical state of anesthesia (MOSSA) was conducted. Also, for patients of ages less than 6 years, we analyzed the performance of cross frequency coupling derived indices in distinguishing the states of wakefulness, MOSSA, and recovery of consciousness (ROC). RESULTS: (1) During MOSSA, EEG power substantially increased with age from infancy to 3-6 years then decreased with age in the theta-gamma frequency bands. The infant group (<1 year) had the highest slow oscillation (SO) power among all age groups. (2) The distinct PAC pattern is absent in patients less than 1 year of age both in SO-alpha and delta-alpha frequency band coupling during propofol induced unconsciousness. The modulation index between delta and alpha oscillations in MOSSA increased with age. (3) Wavelet bicoherence derived indices reach their peaks in the 3-6 years group and then decrease with age growth. (4) The Diag_En index (normalized entropy of the diagonal bicoherence entries of the bicoherence matrix) performed the best at distinguishing different states for ages less than 6 years (p<0.05). CONCLUSIONS: The combination of propofol induction and sevoflurane maintenance exhibited age-dependent EEG power spectra, PAC, and bicoherence, likely related to brain development. These observations suggest new rules for infant and child brain state monitoring during general anesthesia are needed.

Information Integration and Mesoscopic Cortical Connectivity during Propofol Anesthesia.

BACKGROUND: The neurophysiologic mechanisms of propofol-induced loss of consciousness have been studied in detail at the macro (scalp electroencephalogram) and micro (spiking or local field potential) scales. However, the changes in information integration and cortical connectivity during propofol anesthesia at the mesoscopic level (the cortical scale) are less clear. METHODS: The authors analyzed electrocorticogram data recorded from surgical patients during propofol-induced unconsciousness (n = 9). A new information measure, genuine permutation cross mutual information, was used to analyze how electrocorticogram cross-electrode coupling changed with electrode-distances in different brain areas (within the frontal, parietal, and temporal regions, as well as between the temporal and parietal regions). The changes in cortical networks during anesthesia-at nodal and global levels-were investigated using clustering coefficient, path length, and nodal efficiency measures. RESULTS: In all cortical regions, and in both wakeful and unconscious states (early and late), the genuine permutation cross mutual information and the percentage of genuine connections decreased with increasing distance, especially up to about 3 cm. The nodal cortical network metrics (the nodal clustering coefficients and nodal efficiency) decreased from wakefulness to unconscious state in the cortical regions we analyzed. In contrast, the global cortical network metrics slightly increased in the early unconscious state (the time span from loss of consciousness to 200 s after loss of consciousness), as compared with wakefulness (normalized average clustering coefficient: 1.05 ± 0.01 vs. 1.06 ± 0.03, P = 0.037; normalized average path length: 1.02 ± 0.01 vs. 1.04 ± 0.01, P = 0.021). CONCLUSIONS: The genuine permutation cross mutual information reflected propofol-induced coupling changes measured at a cortical scale. Loss of consciousness was associated with a redistribution of the pattern of information integration; losing efficient global information transmission capacity but increasing local functional segregation in the cortical network.

Vascular effects of caffeine found in BOLD fMRI.

The blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) measures neuronal activation indirectly. Previous studies have found aperiodic, systemic low-frequency oscillations (sLFOs, ~0.1 Hz) in BOLD signals from resting state (RS) fMRI, which reflects the non-neuronal cerebral perfusion information. In this study, we investigated the possibility of extracting vascular information from the sLFOs in RS BOLD fMRI, which could provide complementary information to the neuronal activations. Two features of BOLD signals were exploited. First, time delays between the sLFOs of big blood vessels and brain voxels were calculated to determine cerebral circulation times and blood arrival times. Second, voxel-wise standard deviations (SD) of LFOs were calculated to represent the blood densities. We explored those features on the publicly available Myconnectome data set (a 2-year study of an individual subject (Male)), which contains 45 RS scans acquired after the subject had coffee, and 45 coffee-free RS scans, acquired on different days. Our results showed that shorter time delays and smaller SDs were detected in caffeinated scans. This is consistent with the vasoconstriction effects of caffeine, which leads to increased blood flow velocity. We also compared our results with previous findings on neuronal networks from the same data set. Our finding showed that brain regions with the significant vascular effect of caffeine coincide with those with a significant neuronal effect, indicating close interaction. This study provides methods to assess the physiological information from RS fMRI. Together with the neuronal information, we can study simultaneously the underlying correlations and interactions between vascular and neuronal networks, especially in pharmacological studies.

Cerebral circulation time derived from fMRI signals in large blood vessels.

BACKGROUND: The systemic low-frequency oscillation (sLFO) functional (f)MRI signals extracted from the internal carotid artery (ICA) and the superior sagittal sinus (SSS) are found to have valuable physiological information. PURPOSE: 1) To further develop and validate a method utilizing these signals to measure the delay times from the ICAs and the SSS. 2) To establish the delay time as an effective perfusion biomarker that associates with cerebral circulation time (CCT). 3) To explore within subject variations, and the effects of gender and age on the delay times. STUDY TYPE: Prospective. SUBJECTS: In all, 100 healthy adults (Human Connectome Project [HCP], age range 22-36 years, 54 females and 46 males), 56 healthy children (Adolescent Brain Cognitive Development project) were included. FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI) sequence at 3T. ASSESSMENT: The sLFO fMRI signals from the ICAs and the SSSs were extracted from the resting state fMRI data. The maximum cross-correlation coefficients and their corresponding delay times were calculated. The gender and age differences of delay times were assessed statistically. STATISTICAL TESTS: T-tests were conducted to measure the gender differences. The Kruskal-Wallis test was used to detect age differences. RESULTS: Consistent and robust results were found from 80% of the 400 HCP scans included. Negative correlations (-0.67) between the ICA and the SSS signals were found with the ICA signal leading the SSS signal by ∼5 sec. Within subject variation was 2.23 sec at the 5% significance level. The delay times were not significantly different between genders (P = 0.9846, P = 0.2288 for the left and right ICA, respectively). Significantly shorter delay times (4.3 sec) were found in the children than in the adults (P < 0.01). DATA CONCLUSION: We have shown that meaningful perfusion information (ie, CCT) can be derived from the sLFO fMRI signals of the large blood vessels. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1504-1513.

Use of Multiple EEG Features and Artificial Neural Network to Monitor the Depth of Anesthesia.

The electroencephalogram (EEG) can reflect brain activity and contains abundant information of different anesthetic states of the brain. It has been widely used for monitoring depth of anesthesia (DoA). In this study, we propose a method that combines multiple EEG-based features with artificial neural network (ANN) to assess the DoA. Multiple EEG-based features can express the states of the brain more comprehensively during anesthesia. First, four parameters including permutation entropy, 95% spectral edge frequency, BetaRatio and SynchFastSlow were extracted from the EEG signal. Then, the four parameters were set as the inputs to an ANN which used bispectral index (BIS) as the reference output. 16 patient datasets during propofol anesthesia were used to evaluate this method. The results indicated that the accuracies of detecting each state were 86.4% (awake), 73.6% (light anesthesia), 84.4% (general anesthesia), and 14% (deep anesthesia). The correlation coefficient between BIS and the index of this method was 0.892 ( p < 0.001 ). The results showed that the proposed method could well distinguish between awake and other anesthesia states. This method is promising and feasible for a monitoring system to assess the DoA.

A comparison of different synchronization measures in electroencephalogram during propofol anesthesia.

Electroencephalogram (EEG) synchronization is becoming an essential tool to describe neurophysiological mechanisms of communication between brain regions under general anesthesia. Different synchronization measures have their own properties to reflect the changes of EEG activities during different anesthetic states. However, the performance characteristics and the relations of different synchronization measures in evaluating synchronization changes during propofol-induced anesthesia are not fully elucidated. Two-channel EEG data from seven volunteers who had undergone a brief standardized propofol anesthesia were then adopted to calculate eight synchronization indexes. We computed the prediction probability (P K ) of synchronization indexes with Bispectral Index (BIS) and propofol effect-site concentration (C eff ) to quantify the ability of the indexes to predict BIS and C eff . Also, box plots and coefficient of variation were used to reflect the different synchronization changes and their robustness to noise in awake, unconscious and recovery states, and the Pearson correlation coefficient (R) was used for assessing the relationship among synchronization measures, BIS and C eff . Permutation cross mutual information (PCMI) and determinism (DET) could predict BIS and follow C eff better than nonlinear interdependence (NI), mutual information based on kernel estimation (KerMI) and cross correlation. Wavelet transform coherence (WTC) in α and ß frequency bands followed BIS and C eff better than that in other frequency bands. There was a significant decrease in unconscious state and a significant increase in recovery state for PCMI and NI, while the trends were opposite for KerMI, DET and WTC. Phase synchronization based on phase locking value (PSPLV) in δ, θ, α and γ1 frequency bands dropped significantly in unconscious state, whereas it had no significant synchronization in recovery state. Moreover, PCMI, NI, DET correlated closely with each other and they had a better robustness to noise and higher correlation with BIS and C eff than other synchronization indexes. Propofol caused EEG synchronization changes during the anesthetic period. Different synchronization measures had individual properties in evaluating synchronization changes in different anesthetic states, which might be related to various forms of neural activities and neurophysiological mechanisms under general anesthesia.

[Thalamocortical Neural Mass Model Simulation and Study Based on Field Programmable Gate Array].

Using the computer to imitate the neural oscillations of the brain is of great significance for the analysis of brain functions.Thalamocortical neural mass model(TNMM)reflects the mechanisms of neural activities by establishing the relationships between the thalamus and the cortex,which contributes to the understanding of some specific cognitive functions of the brain and the neural oscillations of electroencephalogram(EEG)rhythms.With the increasing complexity and scale of neural mass model,the performance of conventional computer system can not achieve rapid and large-scale model simulation.In order to solve this problem,we proposed a computing method based on Field Programmable Gate Array(FPGA)hardware in this study.The Altera's DSP Builder module combined with MATLAB/Simulink was used to achieve the construction of complex neural mass model algorithm,which is transplanted to the FPGA hardware platform.This method takes full advantage of the ability of parallel computing of FPGA to realize fast simulation of large-scale and complex neural mass models,which provides new solutions and ideas for computer implementation of neural mass models.

[Portable Epileptic Seizure Monitoring Intelligent System Based on Android System].

The clinical electroencephalogram (EEG) monitoring systems based on personal computer system can not meet the requirements of portability and home usage. The epilepsy patients have to be monitored in hospital for an extended period of time, which imposes a heavy burden on hospitals. In the present study, we designed a portable 16-lead networked monitoring system based on the Android smart phone. The system uses some technologies including the active electrode, the WiFi wireless transmission, the multi-scale permutation entropy (MPE) algorithm, the back-propagation (BP) neural network algorithm, etc. Moreover, the software of Android mobile application can realize the processing and analysis of EEG data, the display of EEG waveform and the alarm of epileptic seizure. The system has been tested on the mobile phones with Android 2. 3 operating system or higher version and the results showed that this software ran accurately and steadily in the detection of epileptic seizure. In conclusion, this paper provides a portable and reliable solution for epileptic seizure monitoring in clinical and home applications.

Detection of burst suppression patterns in EEG using recurrence rate.

Burst suppression is a unique electroencephalogram (EEG) pattern commonly seen in cases of severely reduced brain activity such as overdose of general anesthesia. It is important to detect burst suppression reliably during the administration of anesthetic or sedative agents, especially for cerebral-protective treatments in various neurosurgical diseases. This study investigates recurrent plot (RP) analysis for the detection of the burst suppression pattern (BSP) in EEG. The RP analysis is applied to EEG data containing BSPs collected from 14 patients. Firstly we obtain the best selection of parameters for RP analysis. Then, the recurrence rate (RR), determinism (DET), and entropy (ENTR) are calculated. Then RR was selected as the best BSP index one-way analysis of variance (ANOVA) and multiple comparison tests. Finally, the performance of RR analysis is compared with spectral analysis, bispectral analysis, approximate entropy, and the nonlinear energy operator (NLEO). ANOVA and multiple comparison tests showed that the RR could detect BSP and that it was superior to other measures with the highest sensitivity of suppression detection (96.49%, P = 0.03). Tracking BSP patterns is essential for clinical monitoring in critically ill and anesthetized patients. The purposed RR may provide an effective burst suppression detector for developing new patient monitoring systems.

Multi-scale sample entropy of electroencephalography during sevoflurane anesthesia.

The electroencephalogram (EEG) has been widely applied in the assessment of depth of anesthesia (DoA). Recent research has found that multi-scale EEG analysis describes brain dynamics better than traditional non-linear methods. In this study, we have adopted a modified sample entropy (MSpEn) method to analyze anesthetic EEG series as a measure of DoA. EEG data from a previous study consisting of 19 adult subjects undergoing sevoflurane anesthesia were used in the present investigation. In addition to the modified sample entropy method, the well-established EEG indices approximate entropy (ApEn), response entropy (RE), and state entropy (SE) were also computed for comparison. Pharmacokinetic/pharmacodynamic modeling and prediction probability (P k ) were used to assess and compare the performance of the four methods for tracking anesthetic concentration. The influence of the number of scales on MSpEn was also investigated using a linear regression model. MSpEn correlated closely with anesthetic effect. The P k (0.83 ± 0.05, mean ± SD) and the coefficient of determination R (2) (0.87 ± 0.21) for the relationship between MSpEn and sevoflurane effect site concentration were highest for MSpEn (P k : RE = 0.73 ± 0.08, SE = 0.72 ± 0.07, ApEn = 0.81 ± 0.04; R (2): RE = 0.75 ± 0.08, SE = 0.64 ± 0.09, ApEn = 0.81 ± 0.10). Scales 1, 3 and 5 tended to make the greatest contribution to MSpEn. For this data set, the MSpEn is superior to the ApEn, the RE and the SE for tracking drug concentration change during sevoflurane anesthesia. It is suggested that the MSpEn may be further studied for application in clinical monitoring of DoA.

[Analysis of corticomuscular coherence during rehabilitation exercises after stroke].

To better evaluate neuromuscular function of patients with stroke related motor dysfunction, we proposed an effective corticomuscular coherence analysis and coherent significant judgment method. Firstly, the related functional frequency bands in the electroencephalogram (EEG) were extracted via wavelet decomposition. Secondly, coherence were analysed between surface electromyography (sEMG) and sub-bands extracted from EEG. Further more, a coherent significant indicator was defined to quantitatively describe the similarity in certain frequency domain and phase lock activity between EEG and sEMG. Through the analysis of corticomuscular coherence during knee flexion-extension of stroke patients and healthy controls, we found that the stroke patients exhibited significantly lower gamma-band corticomuscular coherence in performing the task with their affected leg, and there was no statistically significant difference between their unaffected lag and the healthy controls, but with the rehabilitation training, the bilateral difference of corticomuscular coherence in patients decreased gradually.

Age-dependent coupling characteristics of bilateral frontal EEG during desflurane anesthesia.

Objectives.The purpose of this study is to investigate the age dependence of bilateral frontal electroencephalogram (EEG) coupling characteristics, and find potential age-independent depth of anesthesia monitoring indicators for the elderlies.Approach.We recorded bilateral forehead EEG data from 41 patients (ranged in 19-82 years old), and separated into three age groups: 18-40 years (n= 12); 40-65 years (n= 14), >65 years (n= 15). All these patients underwent desflurane maintained general anesthesia (GA). We analyzed the age-related EEG spectra, phase amplitude coupling (PAC), coherence and phase lag index (PLI) of EEG data in the states of awake, GA, and recovery.Main results.The frontal alpha power shows age dependence in the state of GA maintained by desflurane. Modulation index in slow oscillation-alpha and delta-alpha bands showed age dependence and state dependence in varying degrees, the PAC pattern also became less pronounced with increasing age. In the awake state, the coherence in delta, theta and alpha frequency bands were all significantly higher in the >65 years age group than in the 18-40 years age group (p< 0.05 for three frequency bands). The coherence in alpha-band was significantly enhanced in all age groups in GA (p< 0.01) and then decreased in recovery state. Notably, the PLI in the alpha band was able to significantly distinguish the three states of awake, GA and recovery (p< 0.01) and the results of PLI in delta and theta frequency bands had similar changes to those of coherence.Significance.We found the EEG coupling and synchronization between bilateral forehead are age-dependent. The PAC, coherence and PLI portray this age-dependence. The PLI and coherence based on bilateral frontal EEG functional connectivity measures and PAC based on frontal single-channel are closely associated with anesthesia-induced unconsciousness.

The Impact of Bispectral Index Monitoring on Outcomes in Spinal Cord Stimulation for Chronic Disorders of Consciousness.

Objective: To observe whether maintaining the appropriate depth of anesthesia with Bispectral Index (BIS) can improve the prognosis of Spinal Cord stimulation (SCS) implantation in patients with chronic Disorders of consciousness (DoC). Methods: 103 patients with DoC undergoing SCS implantation were reviewed, and 83 patients with DoC were included according to the standard of inclusion and exclusion Criteria. Patients were divided into a BIS group (n =45) and a non-BIS group (n =38) according to whether BIS monitoring was used during the operation. The depth of anesthesia in the BIS group was maintained between 40-60. The anesthesiologist adjusted the depth of anesthesia in the non-BIS group according to clinical experience. Relevant information such as disease course, cause, anesthesia time, and operation time were collected. Preoperative CRS-R(preoperative) score, postoperative CRS-R(24h), and postoperative CRS-R(3m) changes were collected. Results: The CRS-R(3m) score in the BIS group was higher than that in the non-BIS group (preoperative), and the difference was statistically significant (P < 0.05). In CRS-R (24h), the BIS group was higher than the non-BIS group, and the difference was statistically significant (X2=8.787, P =0.004). The improvement of consciousness was included in the multivariate Logistic regression analysis model, and it was found that the thalamus was an independent factor affecting the improvement of consciousness (P < 0.05). During follow-up, 1 patient in the BIS group had a decrease in consciousness from MCS- to VS/ UWS and 2 patients in the non-BIS group died during follow-up. Conclusion: Patients can be benefit in hearing in CRS-R (24h). We recommend the use of BIS to monitor the depth of anesthesia in patients with DoC to improve patient outcomes.

Evaluation of brain function in adult patent ductus arteriosus surgery: A multimodal monitoring approach.

Adult patent ductus arteriosus (PDA) repair surgery often involves hypothermic cardiopulmonary bypass (CPB) and is associated with postoperative neurological complications. Our study evaluates brain function during PDA surgery using regional cerebral oxygen saturation (rSO2) and bispectral index (BIS) monitoring to mitigate these complications. Patients were categorized into moderate (26-31 â„ƒ) and mild (32-35 â„ƒ) hypothermia groups. Findings indicate a positive correlation between PDA diameter and pulmonary artery systolic blood pressure, and a strong correlation between delirium and average rSO2-AUC. The mild hypothermia group had longer extubation and hospitalization times. During CPB, rSO2 levels fluctuated significantly, and EEG analysis revealed changes in brain wave patterns. One case of nerve injury in the mild hypothermia group showed incomplete recovery after a year. Our results advocate for moderate hypothermia during CPB in adult PDA repair, suggesting that combined rSO2 and BIS monitoring can reduce neurological complications post-surgery.

Parameter selection in permutation entropy for an electroencephalographic measure of isoflurane anesthetic drug effect.

The permutation entropy (PE) of the electroencephalographic (EEG) signals has been proposed as a robust measure of anesthetic drug effect. The calculation of PE involves the somewhat arbitrary selection of embedding dimension (m) and lag (τ) parameters. Previous studies of PE include the analysis of EEG signals under sevoflurane or propofol anesthesia, where different parameter settings were determined using a number of different criteria. In this study we choose parameter values based on the quantitative performance, to quantify the effect of a wide range of concentrations of isoflurane on the EEG. We analyzed a set of previously published EEG data, obtained from 29 patients who underwent elective abdominal surgery under isoflurane general anesthesia combined with epidural anesthesia. PE indices using a range of different parameter settings (m = 3-7, τ = 1-5) were calculated. These indices were evaluated as regards: the correlation coefficient (r) with isoflurane end-tidal concentration, the relationship with isoflurane effect-site concentration assessed by the coefficient of determination (R (2)) of the pharmacokinetic-pharmacodynamic models, and the prediction probability (PK). The embedding dimension (m) and lag (τ) have significant effect on the r values (Two-way repeated-measures ANOVA, p < 0.001). The proposed new permutation entropy index (NPEI) [a combination of PE(m = 3, τ = 2) and PE(m = 3, τ = 3)] performed best among all the parameter combinations, with r = 0.89(0.83-0.94), R (2) = 0.82(0.76-0.87), and PK = 0.80 (0.76-0.85). Further comparison with previously suggested PE measures, as well as other unrelated EEG measures, indicates the superiority of the NPEI. The PE can be utilized to indicate the dynamical changes of EEG signals under isoflurane anesthesia. In this study, the NPEI measure that combines the PE with m = 3, τ = 2 and that with m = 3, τ = 3 is optimal.

Kendall transfer entropy: a novel measure for estimating information transfer in complex systems.

Objective.Transfer entropy (TE) has been widely used to infer causal relationships among dynamical systems, especially in neuroscience. Kendall transformation provides a novel quantization method for estimating information-theoretic measures and shows potential advantages for small-sample neural signals. But it has yet to be introduced into the framework of TE estimation, which commonly suffers from the limitation of small sample sizes. This paper aims to introduce the idea of Kendall correlation into TE estimation and verify its effect.Approach.We proposed the Kendall TE (KTE) which combines the improved Kendall transformation and the TE estimation. To confirm its effectiveness, we compared KTE with two common TE estimation techniques: the adaptive partitioning algorithm (D-V partitioning) and the symbolic TE. Their performances were estimated by simulation experiments which included linear, nonlinear, linear + nonlinear models and neural mass models. Moreover, the KTE was also applied to real electroencephalography (EEG) recordings to quantify the directional connectivity between frontal and parietal regions with propofol-induced general anesthesia.Main results.The simulation results showed that the KTE outperformed the other two methods by many measures: (1) identifying the coupling direction under a small sample size; (2) the sensitivity to coupling strength; (3) noise resistance; and (4) the sensitivity to time-dependent coupling changes. For real EEG recordings, the KTE clearly detected the disrupted frontal-to-parietal connectivity in propofol-induced unconsciousness, which is in agreement with previous findings.Significance.We reveal that the proposed KTE method is a robust and powerful tool for estimating TE, and is particularly suitable for small sample sizes. The KTE also provides an innovative form of quantizing continuous time series for information-theoretic measures.

The EEG complexity, information integration and brain network changes in minimally conscious state patients during general anesthesia.

Objective.General anesthesia (GA) can induce reversible loss of consciousness. Nonetheless, the electroencephalography (EEG) characteristics of patients with minimally consciousness state (MCS) during GA are seldom observed.Approach.We recorded EEG data from nine MCS patients during GA. We used the permutation Lempel-Ziv complexity (PLZC), permutation fluctuation complexity (PFC) to quantify the type I and II complexities. Additionally, we used permutation cross mutual information (PCMI) and PCMI-based brain network to investigate functional connectivity and brain networks in sensor and source spaces.Main results.Compared to the preoperative resting state, during the maintenance of surgical anesthesia state, PLZC decreased (p< 0.001), PFC increased (p< 0.001) and PCMI decreased (p< 0.001) in sensor space. The results for these metrics in source space are consistent with sensor space. Additionally, node network indicators nodal clustering coefficient (NCC) (p< 0.001) and nodal efficiency (NE) (p< 0.001) decreased in these two spaces. Global network indicators normalized average path length (Lave/Lr) (p< 0.01) and modularity (Q) (p< 0.05) only decreased in sensor space, while the normalized average clustering coefficient (Cave/Cr) and small-world index (σ) did not change significantly. Moreover, the dominance of hub nodes is reduced in frontal regions in these two spaces. After recovery of consciousness, PFC decreased in the two spaces, while PLZC, PCMI increased. NCC, NE, and frontal region hub node dominance increased only in the sensor space. These indicators did not return to preoperative levels. In contrast, global network indicatorsLave/LrandQwere not significantly different from the preoperative resting state in sensor space.Significance.GA alters the complexity of the EEG, decreases information integration, and is accompanied by a reconfiguration of brain networks in MCS patients. The PLZC, PFC, PCMI and PCMI-based brain network metrics can effectively differentiate the state of consciousness of MCS patients during GA.

Propofol modulates neural dynamics of thalamo-cortical system associated with anesthetic levels in rats.

The thalamocortical system plays an important role in consciousness. How anesthesia modulates the thalamocortical interactions is not completely known.  We simultaneously recorded local field potentials(LFPs) in thalamic reticular nucleus(TRN) and ventroposteromedial thalamic nucleus(VPM), and electrocorticographic(ECoG) activities in frontal and occipital cortices in freely moving rats (n = 11). We analyzed the changes in thalamic and cortical local spectral power and connectivities, which were measured with phase-amplitude coupling (PAC), coherence and multivariate Granger causality, at the states of baseline, intravenous infusion of propofol 20, 40, 80 mg/kg/h and after recovery of righting reflex. We found that propofol-induced burst-suppression results in a synchronous decrease of spectral power in thalamus and cortex (p < 0.001 for all frequency bands). The cross-frequency PAC increased by propofol, characterized by gradually stronger 'trough-max' pattern in TRN and stronger 'peak-max' pattern in cortex. The cross-region PAC increased in the phase of TRN modulating the amplitude of cortex. The functional connectivity (FC) between TRN and cortex for α/ß bands also significantly increased (p < 0.040), with increased directional connectivity from TRN to cortex under propofol anesthesia. In contrast, the corticocortical FC significantly decreased (p < 0.047), with decreased directional connectivity from frontal cortex to occipital cortex. However, the thalamothalamic functional and directional connectivities remained largely unchanged by propofol anesthesia.  The spectral powers and connectivities are differentially modulated with the changes of propofol doses, suggesting the changes in neural dynamics in thalamocortical system could be used for distinguishing different vigilance levels caused by propofol. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09912-0.