Neural correlates of category learning in monkey inferior temporal cortex.

We trained two monkeys implanted with multi-electrode arrays to categorize natural images of cats and dogs, in order to observe changes in neural activity related to category learning. We recorded neural activity from area TE, which is required for normal learning of visual categories based on perceptual similarity. Neural activity during a passive viewing task was compared pre- and post-training. After the category training, the accuracy of abstract category decoding improved. Specifically, the proportion of single units with category selectivity increased, and units sustained their category-specific responses for longer. Visual category learning thus appears to enhance category separability in area TE by driving changes in the stimulus selectivity of individual neurons and by recruiting more units to the active network.

The histamine H1 receptor antagonist hydroxyzine enhances sevoflurane and propofol anesthesia: A quantitative EEG study.

OBJECTIVE: The aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia. METHODS: We analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50-60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics. RESULTS: Hydroxyzine increased the α bicoherence peaks in both sevoflurane anesthesia (mean difference, 11.2%; 95% confidence interval (CI), 7.6 to 14.8; P < 0.001) and propofol anesthesia (mean difference, 5.6%; 95% CI, 1.7 to 9.4; P = 0.008). Hydroxyzine increased the averaged δ bicoherence values in both sevoflurane anesthesia (mean difference, 5.5%; 95% CI, 2.1 to 8.8; P = 0.003) and propofol anesthesia (mean difference, 3.9%; 95% CI, 1.0 to 6.8; P = 0.011). CONCLUSIONS: Hydroxyzine enhances both sevoflurane anesthesia and propofol anesthesia probably by facilitation of GABAergic neural circuit mechanisms. SIGNIFICANCE: The findings provide a new insight into the role of histaminergic neurons during general anesthesia in humans.

A convolutional neural network for estimating synaptic connectivity from spike trains.

The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset. Here we present another method using a Convolutional Neural Network for Estimating synaptic Connectivity from spike trains. After adaptation to huge amounts of simulated data, this method robustly captures the specific feature of monosynaptic impact in a noisy cross-correlogram. There are no user-adjustable parameters. With this new method, we have constructed diagrams of neuronal circuits recorded in several cortical areas of monkeys.

Hierarchical Poincaré analysis for anaesthesia monitoring.

Although the degree of dispersion in Poincaré plots of electroencephalograms (EEG), termed the Poincaré-index, detects the depth of anaesthesia, the Poincaré-index becomes estranged from the bispectral index (BIS) at lighter anaesthesia levels. The present study introduces Poincaré-index20-30 Hz, targeting the 20- to 30-Hz frequency, as the frequency range reported to contain large electromyogram (EMG) portions in frontal EEG. We combined Poincaré-index20-30 Hz with the conventional Poincaré-index0.5-47 Hz using a deep learning technique to adjust to BIS values, and examined whether this layered Poincaré analysis can provide an index of anaesthesia level like BIS. A total of 83,867 datasets of these two Poincaré-indices and BIS-monitor-derived parameters were continuously obtained every 3 s from 30 patients throughout general anaesthesia, and were randomly divided into 75% for a training dataset and 25% for a test dataset. Two Poincaré-indices and two supplemental EEG parameters (EMG70-110 Hz, suppression ratio) in the training dataset were trained in a multi-layer perceptron neural network (MLPNN), with reference to BIS as supervisor. We then evaluated the trained MLPNN model using the test dataset, by comparing the measured BIS (mBIS) with BIS predicted from the model (PredBIS). The relationship between mBIS and PredBIS using the two Poincaré-indices showed a tight linear regression equation: mBIS = 1.00 × PredBIS + 0.15, R = 0.87, p < 0.0001, root mean square error (RMSE) = 7.09, while the relationship between mBIS and PredBIS simply using the original Poincaré-index0.5-47 Hz was weaker (R = 0.82, p < 0.0001, RMSE = 7.32). This suggests the 20- to 30-Hz hierarchical Poincaré analysis has potential to improve on anaesthesia depth monitoring constructed by simple Poincaré analysis.

The fundamental contribution of the electromyogram to a high bispectral index: a postoperative observational study.

The electromyogram (EMG) activity has been reported to falsely increase BIS. Conversely, EMG seems necessary to constitute the high BIS indicative of an awake condition, and may play a fundamental role in calculating BIS, rather than distorting the appropriate BIS. However, exactly how EMG is associated with a high BIS remains unclear. We intended to clarify the respective contributions of EMG and various electroencephalogram (EEG) parameters to high BIS. In 79 courses of anaesthesia, BIS monitor-derived EMG parameters (EMGLOW), and other processed EEG parameters [SEF95 (spectral edge frequency 95%), SynchFastSlow (bispectral parameter), BetaRatio (frequency parameter), total power subtypes in five frequency range], were obtained simultaneously with BIS, every 3 s. These EEG parameters were used for receiver operating characteristic (ROC) analysis of detecting three BIS levels (BIS > 80, BIS > 70, and BIS > 60) to assess their diagnosabilities. A total of 218,418 data points derived from 79 cases were used for analysis. Area under the ROC curve (AUC) was calculated and optimal cut-off (threshold) was determined by Youden index. As the results, for detecting BIS > 80, the AUC of EMGLOW was 0.975 [0.974-0.977] (mean [95% confidence interval]), significantly higher than any other processed EEG parameters such as BetaRatio (0.832 [0.828-0.835]), SEF95 (0.821 [0.817-0.826]) and SynchFastSlow (0.769 [0.764-0.774]) (p < 0.05 each). The threshold of EMGLOW for detecting BIS > 80 was 35.7 dB, with high sensitivity (92.5%) and high specificity (96.5%). Our results suggest EMG contributes considerably to the diagnosis of high BIS, and is particularly essential for determining BIS > 80.

Dopamine D2-receptor Antagonist Droperidol Deepens Sevoflurane Anesthesia.

BACKGROUND: Although midbrain dopaminergic pathways are known to contribute to arousal and emergence from anesthesia, few reports exist regarding the anesthetic effects of dopamine D2 receptor antagonism in humans. This study examined the effect of the D2 receptor antagonist droperidol on sevoflurane anesthesia by examining α and slow wave electroencephalogram oscillations. METHODS: Forty-five patients, age 20 to 60 yr, were enrolled. Frontal electroencephalograms were continuously collected for offline analysis via Bispectral Index monitoring. After induction of anesthesia, end-tidal sevoflurane concentration was deliberately maintained at 1%, and intravenous droperidol (0.05 mg/kg bolus) was administered. Electroencephalogram changes were examined in power spectrum and bicoherence, before and 10 min after droperidol injection, then compared using the Wilcoxon signed-ranks test and/or paired t test. RESULTS: Droperidol significantly augmented the α-bicoherence peak induced by sevoflurane from 30.3% (24.2%, 42.4%) to 50.8% (41.7%, 55.2%) (median [25th, 75th percentiles]; P < 0.0001), Hodges-Lehman median difference, 15.8% (11.3 to 21.4%) (95% CI). The frequency of the α-bicoherence peak was simultaneously shifted to the lower frequency; from 11.5 (11.0, 13.0) to 10.5 (10.0, 11.0) Hz (median [25th, 75th percentiles], P < 0.0001). Averaged bicoherence in the δ-θ area increased conspicuously from 17.2% (15.6 to 18.7%) to 25.1% (23.0 to 27.3%) (mean [95% CI]; P < 0.0001), difference, 8.0% (6.0 to 9.9%). CONCLUSIONS: Droperidol augments both α and δ-θ bicoherences while shifting the α-bicoherence peaks to lower frequencies, and enhances the effect of sevoflurane anesthesia on the electroencephalogram via γ-aminobutyric acid-mediated oscillatory network regulation.

Electroencephalographic monitoring during sevoflurane anaesthesia in an amyotrophic lateral sclerosis patient with locked-in state.

Recently, the cognitive abilities of patients with amyotrophic lateral sclerosis (ALS) have been found to be impaired along with the neurodegeneration of motor neurons. Electroencephalography (EEG) of end-stage ALS patients has reportedly shown specific features based on neuronal network modulations, differing from EEG of other patients with cognitive failure and dementia. However, EEG of end-stage ALS patients during anaesthesia has not yet been reported. A 64-year-old male ALS patient with locked-in state (LIS), supported by tracheostomy positive-pressure ventilation (TPPV) and enteral nourishment for 9years, underwent scheduled general anaesthesia for repair of a fractured mandible. He could blink and open his eyes, but seldom opened or closed his eyes on instruction. Sevoflurane anaesthesia was induced under continuous EEG monitoring with bispectral index (BIS), which is commonly used to examine the level of anaesthesia. Prominent alpha oscillations with lower peak frequency and high amplitude appeared during anaesthesia, differing from the characteristics of EEG seen in patients with general cognitive failure. Conversely, BIS reflected the sevoflurane concentration in this ALS patient, similar to healthy individuals, and BIS monitoring was useful for estimating the depth of anaesthesia. The prominent alpha oscillation revealed in this rare case report may suggest modulation of the functional neuronal network system during anaesthesia in patients with progressive ALS, in a manner quite different from typical dementia patients. EEG abnormalities in the present ALS patient did not influence the availability of BIS monitoring.

Unpredictable interference of new transcranial motor-evoked potential monitor against the implanted pacemaker.

Recently, NuVasive NV-M5 nerve monitoring system, a new transcranial motor-evoked potential (TcMEP) monitor, has been introduced with the spread of flank-approach spinal operations such as extreme lateral interbody fusion, to prevent nerve damage. Conventional TcMEP monitors use changes in MEP wave patterns, such as amplitude and/or latency, whereas the NV-M5 nerve monitor system first measures the MEP baseline waveform from the transcranial-evoked potential then measures the electric current necessary to obtain the standard of the previous baseline wave pattern at subsequent monitoring times. The NV-M5 monitor determines nerve damage according to the increase in necessary electric current threshold. The NV-M5 monitor also uses a local electrical stimulation mode to monitor the safety of setting screws into the lumbar vertebrae. In this way, various electrical stimulations with various durations and frequencies are used, and electrical noise may result in unpredictable interference with cardiac pacemakers. We performed anesthetic management of extreme lateral interbody fusion surgery using the NV-M5 in a patient with an implanted pacemaker, during which TcMEP stimulation caused interference with the implanted pacemaker.

[Serious Coagulation Dysfunction in a Patient with Gallstone-related Cholecystitis Successfully Treated with Vitamin K].

An 85-year-old woman with a diagnosis of choledocholithiasis due to common duct stones gradually developed severe coagulation dysfunction over the course of 27 days after hospitalization. Initial clinical findings were fever, general malaise, and obstructive jaundice. She was treated with fasting, and received cephem antibiotics containing N-methyl-thio-tetrazole. Because the common duct stones were not removed endoscopically, cholecystectomy was scheduled. Coagulation on admission was normal, but gradually became impaired. On the scheduled day of the operation, 27 days after hospitalization, coagulation [both prothrombin time (PT) and activated partial thromboplastin time (APTT)] were severely impaired PT, < 10%; PT-international normalized ratio, 6.29; and APTT, 71.6 s. No other abnormalities were identified. Surgery was postponed and antibiotics were discontinued. Simultaneously, administration of vitamin K was initiated. Six days after starting vitamin K, coagulation dysfunction had resolved and the surgery was safely performed under general anesthesia combined with thoracic epidural anesthesia. Care is warranted regarding coagulation dysfunction due to vitamin K deficiency in patients with hepatobiliary disease treated by fasting and antibiotics.

Effect-site concentrations of remifentanil causing bradycardia in hypnotic and non-hypnotic patients.

Although the induction of anaesthesia with remifentanil often causes bradycardia, the relationship between the effect-site concentration (Ce) of remifentanil and instantaneous heart rate (HR) has remained unclear. The present study examined the relationship between instantaneous HR and remifentanil Ce at the induction of anaesthesia with and without propofol hypnosis, to facilitate safe management of anaesthesia induction with remifentanil. Instantaneous HR was calculated every 5 s using an electrocardiographic real-time analysis system (MemCalc/Makin2; GMS, Tokyo, Japan). At the beginning of anaesthesia induction, continuous infusion of remifentanil (1 µg min-1 kg-1) preceded hypnosis with propofol in 13 patients [non-hypnosis group; mean age, 67.8 (17.5) years], while propofol bolus (30-50 mg) was injected together with continuous remifentanil medication in 18 patients [hypnosis group; mean age, 62.9 (16.5) years]. Remifentanil Ce was estimated every 5 s using the three-compartment model proposed by Minto et al. and the relationship between estimated remifentanil Ce and instantaneous HR was examined. In the hypnosis group, HR was significantly lower than basal HR when remifentanil Ce was increased to 3.5 ng ml-1 (p < 0.05), whereas no significant HR reduction was found in the non-hypnosis group until remifentanil Ce reached >5 ng ml-1 (p < 0.05). The induction of anaesthesia using remifentanil with propofol hypnotics significantly reduces HR even in a low remifentanil Ce insufficient to suppress the cardiovascular response at tracheal intubation. Preparations to treat bradycardia are recommended for the safe management of anaesthesia induction when remifentanil is combined with hypnotics.

[Use and Safety of Preoperative Oral Rehydration Therapy Using a Jelly Type Oral Rehydration Solution].

BACKGROUND: Traditionally, perioperative nutritional management centered on fluid therapy, but in recent years, with the spread of enhanced recovery after surgery (ERAS) protocols, the utility of oral rehydration therapy (ORT) has been reported. There are few reports, however, on the safety of using jelly type oral rehydration solutions for ORT. We examined the effects of OS-1 jelly on gastric fluid and investigated its safety. METHODS: A total of 147 patients (age range, 4-91 years), scheduled for elective surgery at our institution for whom ORT was indicated, were enrolled in this study. If the surgery was scheduled for the morning, patients were given two bottles of 200 g OS-1 jelly during the previous evening meal. If surgery was scheduled for the afternoon, two additional 200 g bottles were given to the patient with the morning meal on the day of surgery. Patients were allowed to drink water until two hours before the surgery. Gastric fluid was aspirated with a gastric tube after anesthesia induction, after which, volume and pH were measured. RESULTS: In all cases, gastric content was aspirated as a liquid, not a jelly. The volume and pH were 11.4 ± 14.6 ml and 2.8 ± 2.2, respectively. No major difference was seen in comparison with the data for OS-1 liquid. No postoperative aspiration pneumonia or reflux of gastric contents at the time of anesthesia induction was seen in any of the patients. CONCLUSIONS: From the present findings, if the time of water intake is strictly controlled, preoperative rehydration therapy using jelly-type oral rehydration solution is thought to be safe and comparable to liquid solution regarding its effects on gastric fluid.

Appetitive and aversive information coding in the primate dorsal raphé nucleus.

Serotonin is known to play a key role in the regulation of emotional behavior. There have been conflicting hypotheses about whether the central serotonergic system is involved in positive or negative emotional information processing. To reveal whether and how such opposing information processing can be achieved by single neurons in the dorsal raphé nucleus (DRN), the major source of serotonin in the forebrain, we recorded the activity of DRN neurons while monkeys were conditioned in a Pavlovian procedure with two distinct contexts: an appetitive block where a reward was available; and an aversive one where an airpuff was delivered. We found that single DRN neurons were involved in several aspects of both appetitive and aversive information processing. First, more than half of the recorded DRN neurons discriminated between appetitive and aversive contexts by tonic changes in their activity. In the appetitive context, they then kept track of the expected reward value indicated by the conditioned stimuli. Some of them also encoded an error between the obtained and expected values. In the aversive context, the same neurons maintained tonic modulation in their activity throughout the block. However, modulation of their responses to aversive task events depending on airpuff probability was less common. Together, these results indicate that single DRN neurons encode both appetitive and aversive information, but over differing time scales: relatively shorter for appetitive, and longer for aversive. Such temporally distinct processes of value coding in the DRN may provide the neural basis of emotional information processing in different contexts.

Poincaré analysis of the electroencephalogram during sevoflurane anesthesia.

OBJECTIVE: The Poincaré plot is a two-dimensional state-space approach, where a timed signal is plotted against itself after a time delay, enabling determination of the dynamic nature of signals. Quantification of the Poincaré plot is a candidate for estimating anesthesia-dependent changes in the electroencephalogram (EEG). METHODS: In 20 patients, at four different states of anesthesia (0.5%, 1%, 2% and 3% sevoflurane), frontal EEG signals (10s) were used to construct Poincaré plots. The plot pattern was quantified by the standard deviation of the voltage dispersion along the line of identity (SD2), the standard deviation perpendicular to the line of identity (SD1) and their ratio (SD1/SD2), and compared using spectral EEG features. RESULTS: A significant stepwise decrease in the SD1/SD2 ratio was observed with each stepwise increase in sevoflurane concentration (p<0.001 for each). From 0.5% to 3% sevoflurane anesthesia, the ratio of relative ß power to δ power (ß/δ) was highly correlated with SD1/SD2 (R=0.92). CONCLUSIONS: The Poincaré plot of the frontal EEG can detect the significant changes in the depth of anesthesia induced by different sevoflurane concentrations. SIGNIFICANCE: The Poincaré plot is a useful technique for detecting the EEG changes induced by anesthesia.

Simultaneous bicoherence analysis of occipital and frontal electroencephalograms in awake and anesthetized subjects.

OBJECTIVE: Occipital electroencephalogram (EEG) activity is known to be different from the frontal EEG during wakefulness and anesthesia. However, less is known about occipital non-linear dynamics analyzed by EEG-bicoherence, which can reflect the oscillatory features that are dependent on thalamocortical modulation. METHODS: Forty patients were anesthetized using sevoflurane (1% or 3%) combined with remifentanil. Frontal and occipital EEGs were simultaneously collected, and bicoherence was analyzed before and after induction of anesthesia. RESULTS: Occipital awake EEGs often demonstrate a bicoherence α peak, differing from frontal awake EEGs in the absence of bicoherence growth. With 1% sevoflurane, occipital α bicoherence disappeared and frontal α bicoherence peaks appeared. Although 3% sevoflurane caused an increase in occipital δ-θ normalized power, similar to the frontal region (peak relative δ-θ power, 13.1 ± 2.2% vs. 12.2 ± 2.7%, p>0.05), occipital bicoherence showed no growth in any frequency area, contrasting with the frontal bicoherence spectrum with a conspicuous peak in the δ-θ area (19.8 ± 8.9 vs. 43.6 ± 13.8, p<0.05). CONCLUSIONS: The occipital bicoherence spectrum in the peri-anesthesia period is quite different from the frontal bicoherence spectrum, which is not usually obvious in the power spectrum. SIGNIFICANCE: Nonlinear regulation of the occipital EEG is different from the frontal EEG during every stage of anesthesia.

Neonatal electroencephalography shows low sensitivity to anesthesia.

This study examined EEG under clinical anesthesia in neonates and infants, to clarify how growth affects EEG during anesthesia. Subjects comprised 62 neonates and infants. Patients were divided into four groups according to age: Group 1 (neonates), <1 month; Group 2, 1-2 months; Group 3, 3-5 months; and Group 4, 6 months to 2 years. Anesthesia was maintained with sevoflurane and fentanyl and/or caudal block. At four points of sevoflurane concentration (0.5%, 1%, 1.5%, and 2%), 90% spectral edge frequency (SEF90), burst suppression ratio (BSR), relative beta ratio (RBR) and approximate entropy (ApEn) were analyzed. In Group 4, SEF90, BSR, RBR and ApEn changes were dependent on the concentration of anesthesia, along with changes in sevoflurane concentration from 0.5% to 2% (from 14.3 (2.7) [mean (SD)] Hz to 8.2 (3.8) Hz, from 0.0 to 0.32 (0.36), from -1.58 (0.14) to -1.10 (0.15), and from 0.56 (0.25) to 0.24 (0.25) respectively; p<0.05 each). Conversely, these processed EEG parameters in Group 1 showed little anesthesia-dependent change under sevoflurane concentrations between 0.5% and 2% (SEF90: 7.3 (1.2) Hz vs. 7.7 (2.1) Hz; BSR: 0.51 (0.20) vs. 0.62 (0.29); RBR: -1.00 (0.17) vs. -1.03 (0.27); ApEn: 0.32 (0.18) vs. 0.25 (0.14), respectively). The unique EEG features of neonates during anesthesia rapidly change to the usual anesthesia-dependent patterns seen in older children, with a boundary of 3-5 months old. In infants younger than 6 months old, neural network regulation reflected in EEG by anesthesia is weak.