EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery

The first attempts to introduce computerized power spectrum analysis of the electroencephalogram (EEG) as an intraoperative anaesthesia monitoring device started approximately 30 years ago. Since that time, the effects of various anaesthetic agents, sedative and analgesic drugs on the EEG pattern have been addressed in numerous studies in human patients and different animal species. These studies revealed dose-dependent changes in the EEG power spectrum for many intravenous and volatile anaesthetics. Moreover, EEG responses evoked by surgical stimuli during relative light levels of surgical anaesthesia have been classified as 'arousal' and 'paradoxical arousal' reaction, previously referred to as 'desynchronization' and 'synchronization', respectively. Contrasting reports on the correlation between quantitative EEG (QEEG) variables derived from power spectrum analysis (i.e. spectral edge frequency, median frequency) and simultaneously recorded clinical signs such as movement and haemodynamic responses, however, limited the routine use of intraoperative EEG monitoring. In addition, the appearance of EEG burst suppression pattern and isoelectricity at clinically relevant concentrations/doses of newer general anaesthetics (i.e. isoflurane, sevoflurane, propofol) may have weakened the dose-related EEG changes previously reported. Despite these findings, the EEG power spectrum analysis may still provide valuable information during intraoperative monitoring in the individual subject. The information obtained from EEG power spectrum analysis may be further supplemented by newer EEG indices such as bispectral index and approximate entropy or other neurophysiological monitors including auditory evoked potentials or somatosensory evoked potentials.     

The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs

The noble gas xenon seems to have minimal cardiovascular side-effects and so may be an ideal anaesthetic agent when investigating cardiovascular physiology. In comparison with standard modern anaesthetics, we investigated the haemodynamic and hormonal effects of xenon in Beagle dogs. After a 30 min baseline period, anaesthesia was induced with propofol and maintained with either (1) 1.2% isoflurane/70% nitrous oxide (N(2)O), (2) 0.8% isoflurane/0.5 microg/kg/min remifentanil or (3) 63% xenon/0.5 microg/kg/min remifentanil (n = 6 per group). Haemodynamics were recorded and blood samples taken before and 60 min after induction. Mean arterial blood pressure (MAP) was higher in conscious dogs than during isoflurane/N(2)O (86 +/- 2 vs. 65 +/- 2 mmHg, mean +/- SEM) and isoflurane/remifentanil anaesthesia (95 +/- 2 vs. 67 +/- 3 mmHg), whereas MAP did not decrease significantly in response to xenon/remifentanil anaesthesia (96 +/- 4 vs. 85 +/- 6 mmHg). Bradycardia was present during isoflurane/remifentanil (54 +/- 2/min) and xenon/remifentanil (40 +/- 3/min), but not during isoflurane/N(2)O anaesthesia (98 +/- 3/min, P < 0.05). Xenon/remifentanil anaesthesia induced the highest reduction in cardiac output (CO) (-61%), and the highest increase in systemic vascular resistance (+120%) among all treatment groups (P < 0.05). A simultaneous increase in endogenous adrenaline and noradrenaline concentrations could only be observed in the xenon/remifentanil group, whereas angiotensin II and vasopressin concentrations increased in all groups. In conclusion, xenon/remifentanil anaesthesia maintains MAP but reduces heart rate and CO and is associated with a considerable stimulation of vasopressor hormones in Beagle dogs. Therefore, xenon/remifentanil exerts a new quality of adverse haemodynamic effects different from volatile anaesthetics and may not perform better during studies of cardiovascular physiology.     

Single-sweep cortical somatosensory evoked potentials: N20 and evoked bursts in sevoflurane anaesthesia

Cortical evoked responses to median nerve stimulation were recorded from 21 subjects during sevoflurane anaesthesia at the level of burst suppression in EEG. The N20/P22 wave had the typical form of a negative wave postcentrally, and positive precentrally. The amplitude exceeded 4 μV in all patients, making it easily visible without averaging on the low-amplitude suppression. These results show that two kinds of somatosensory evoked potential can be studied without averaging during EEG suppression in deep anaesthesia. One is the localised N20/P22 wave, which is seen regularly during suppression after stimuli with intervals exceeding 1 s. The other is the burst, involving the whole cortex, which is not evoked by every stimulus. We suggest that somatosensory evoked potentials can be monitored during sevoflurane-induced EEG suppression, and often can be evaluated reliably from a couple of single sweeps with stimulation interval exceeding 1 s. The enhancement of early cortical components of SEP, their adaptation to repeated stimuli, and the disappearance of later polysynaptic components during EEG suppression, give new possibilities to study the generators of SEP and the different effects of anaesthetics.     

Description of a technique for anaesthetizing pregnant ewes for fetal surgery

General anaesthesia in 12 pregnant ewes undergoing surgery for fetal physiological research was supplemented with an intravenous infusion of remifentanil. This allowed us to employ a lighter plane of surgical anaesthesia and to use intermittent positive pressure ventilation. Our aim was to improve fetomaternal outcome. We monitored maternal pulse, blood pressure, transcutaneous oxygen saturation and end-tidal carbon dioxide levels. Remifentanil doses of 0.75-2.0 microg/kg/min were needed and typically this allowed halothane concentrations of 1-1.5% to be used for maintenance of anaesthesia. Surgery lasted up to 2.5 h. All 12 ewes and their singleton fetuses survived the peri- and postoperative period in good condition.     

NeuMonD: a tool for the development of new indicators of anaesthetic effect.

Electroencephalogram (EEG) signals and auditory evoked potentials (AEPs) have been suggested as a measure of depth of anaesthesia, because they reflect activity of the main target organ of anaesthesia, the brain. The online signal processing module NeuMonD is part of a PC-based development platform for monitoring "depth" of anaesthesia using EEG and AEP data. NeuMonD allows collection of signals from different clinical monitors, and calculation and simultaneous visualisation of several potentially useful parameters indicating "depth" of anaesthesia using different signal processing methods. The main advantage of NeuMonD is the possibility of early evaluation of the performance of parameters or indicators by the anaesthetist in the clinical environment which may accelerate the process of developing new, multiparametric indicators of anaesthetic "depth".     

Incidence of epileptiform EEG activity in children during mask induction of anaesthesia with brief administration of 8% sevoflurane

Background

A high incidence of epileptiform activity in the electroencephalogram (EEG) was reported in children undergoing mask induction of anaesthesia with administration of high doses of sevoflurane for 5 minutes and longer. This study was performed to investigate whether reducing the time of exposure to a high inhaled sevoflurane concentration would affect the incidence of epileptiform EEG activity. It was hypothesized that no epileptiform activity would occur, when the inhaled sevoflurane concentration would be reduced from 8% to 4% immediately after the loss of consciousness.

Methodology/Principal Findings

70 children (age 7–96 months, ASA I–II, premedication with midazolam) were anaesthetized with 8% sevoflurane in 100% oxygen via face mask. Immediately after loss of consciousness, the sevoflurane concentration was reduced to 4%. EEGs were recorded continuously and were later analyzed visually with regard to epileptiform EEG patterns. Sevoflurane at a concentration of 8% was given for 1.2±0.4 min (mean ± SD). In 14 children (20%) epileptiform EEG patterns without motor manifestations were observed (delta with spikes (DSP), rhythmic polyspikes (PSR), epileptiform discharges (PED) in 10, 10, 4 children (14%, 14%, 6%)). 38 children (54%) had slow, rhythmic delta waves with high amplitudes (DS) appearing on average before DSP.

Conclusions/Significance

The hypothesis that no epileptiform potentials would occur during induction of anaesthesia with a reduction of the inspired sevoflurane concentration from 8% to 4% directly after LOC was not proved. Even if 8% sevoflurane is administered only briefly for induction of anaesthesia, epileptiform EEG activity may be observed in children despite premedication with midazolam.     

Bispectral analysis does not differentiate between anaesthesia EEG and a linear random process]

Bispectral analysis of the electroencephalogram (EEG) has been used to monitor depth of anaesthesia. In the majority of publications this has involved the use of the so called BIS-Index TM (Aspect Medical Systems, Inc.). The exact relationship of this index to such bispectral parameters as the bispectrum and bicoherence has not yet been reported. If the EEG is considered as a linear random process, bicoherence is trivial, i.e. it is independent of the EEG frequency. The aim of this study was to determine the proportion of EEG epochs with non-trivial bicoherence during isoflurane/N20 anaesthesia. We reanalyzed 25.5 hours of digitalised EEG signal from 9 patients undergoing gynaecological surgery. The test developed by Hinich for Gaussian distribution and linearity was then applied. The test was validated using various synthetic surrogate data: Gaussian random data, the z-component of the Lorenz attractor, the phase randomized EEG and the phase randomized z-component of the Lorenz attractor. The percentage of epochs (8.192 s, 1024 data points) with non-trivial bicoherence was: Lorenz data 95.4%, phase randomized Lorenz data 9.4%, synthetic Gaussian data 14.8%, original EEG 9.1%, phase randomized EEG 5.1%. The original EEG data were not found to contain a higher percentage of epochs with non-trivial bicoherence than the phase randomized data and the synthetic Gaussian data. We conclude that bispectral analysis does not substantially add to the information obtained with other methods of quantitative EEG analysis.     

Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia

Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (≥3 g/m² die), 4 with standard dose (100 mg/m² die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6 months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.     

Intraperitoneal propofol and propofol fentanyl, sufentanil and remifentanil combinations for mouse anaesthesia

The combination of propofol and a rapid-acting opioid, such as fentanyl, sufentanil or remifentanil, is a relatively safe, total intravenous anaesthesia technique, commonly used in humans and which has been investigated in laboratory animals. The objective of this study was to evaluate these combinations for anaesthesia of mice by the intraperitoneal (i.p.) route. Sixty-seven mice, divided into groups of four, were used to test 28 combinations of propofol alone and propofol with fentanyl, sufentanil or remifentanil administered i.p. The dose ranges of drugs studied were propofol 50-200 mg/kg, fentanyl 0.2-0.4 mg/kg, sufentanil 0.05-0.1 mg/kg and remifentanil 0.2-1.0 mg/kg. The loss of righting reflex (RR) and the loss of pedal withdrawal reflex (PWR) were recorded along with the duration and quality of recovery. The results obtained in these studies were unpredictable. The same dose combinations of propofol and opioids were associated with different responses in different individuals. Higher doses did not induce loss of RR and PWR in all animals and were associated with high mortality rates. An adequate hypnotic level was only observed with higher doses of propofol. The synergistic effect of propofol and the opioids was not sufficient to allow surgical procedures. Animals that reached PWR loss showed tail rigidity, shaking limbs and scratched their heads with their forefeet. Higher opioid doses induced respiratory depression and higher death rates. The inconsistency between and within groups may be associated with the i.p. route. The results reported here show that the i.p. route is not appropriate for mouse anaesthesia using propofol alone or in combination with fentanyl, sufentanil or remifentanil.     

Suppression of F-VEP during isoflurane-induced EEG suppression

We recorded visual evoked potentials (VEPs) to flash stimuli in moderately deep anaesthesia when EEG showed burst suppression pattern. Flash VEPs could consistently be recorded in all 8 test subjects during bursts but not during suppressions. We conclude that during isoflurane-induced EEG suppression VEPs to flash stimuli are also suppressed. This effect should be taken into account in evoked potential testing during anaesthesia.     

Post-radiation effect on the interhemispheric asymmetry in EEG and thermography characteristics

Complex analysis of EEG and thermographic parameters carried out in 10 healthy subjects and 34 patients, Chernobyl clean-up participants revealed a correlation between EEG and brain temperature changes in the baseline state and during mental arithmetic. During cognitive activity the maximal increase in the average EEG coherence and temperature shifts in healthy subjects were observed in the left frontotemporal and right parietotemporal areas. In patients changes in both parameters under study were most pronounced, the interhemispheric relations were impaired. The visual analysis revealed "flat" and "hypersynchronous" EEG types in patients. The dominant pathologic activity in the betal range indicative of mediobasal and oral brainstem lesions was characteristic of the flat EEG. This type of activity was observed in 60% of patients. In these cases, a general decrease in EEG coherence and temperature was most pronounced in the left hemisphere. The hypersynchronou EEG type (40% patients) was characterized by paroxysmal activity in the theta and alpha ranges suggesting diencephalic brain lesions. In these cases, EEG coherence and temperature were more variable; changes in the right hemisphere were significant, be it increase or decrease. Our complex approach to investigation of brain activity in different aspects seems to be promising in estimation of the brain functional state both in healthy persons and patients in remote terms after exposure to radiation. The specific hemispheric temperature changes revealed in Chernobyl patients especially during cognitive activity can be the sequels of postradiation disorders of vascular neuro-circulation. The EEG findings suggest subcortical disorders at different levels (diencephalic or brainstem) and functional failure of the right or left hemispheres in remote terms after exposure to radiation.     

Population pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery

Background

The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Methods

We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied. Arterial blood samples taken prior to, during and after CPB were analyzed for remifentanil concentrations using a validated gas-chromatographic mass-spectrophotometric assay. We used population mixed-effects modeling to characterize remifentanil pharmacokinetics. The final model was evaluated by its predictive performance.

Results

The pharmacokinetics of remifentanil was described by a 1-compartment model with adjustments for CPB. Population mean parameter estimates were 1.41 L for volume of distribution (V) and 0.244 L/min for clearance. V was increased during CPB and post-CPB to 2.41 times the pre-CPB value. The median prediction error and the median of individual median absolute prediction error were 2.44% and 21.6%, respectively.

Conclusion

Remifentanil dosage adjustments are required during and after CPB due to marked changes in the V of the drug. Simulations indicate that a targeted blood concentration of 14 ng/mL is achieved and maintained in 50% of typical patients by administration of an initial dose of 18 μg remifentanil followed by an infusion of 3.7 μg/min before, during and post-CPB, supplemented with a bolus dose of 25 μg given at the start of CPB.     

An empirical EEG analysis in brain death diagnosis for adults

Electroencephalogram (EEG) is often used in the confirmatory test for brain death diagnosis in clinical practice. Because EEG recording and monitoring is relatively safe for the patients in deep coma, it is believed to be valuable for either reducing the risk of brain death diagnosis (while comparing other tests such as the apnea) or preventing mistaken diagnosis. The objective of this paper is to study several statistical methods for quantitative EEG analysis in order to help bedside or ambulatory monitoring or diagnosis. We apply signal processing and quantitative statistical analysis for the EEG recordings of 32 adult patients. For EEG signal processing, independent component analysis (ICA) was applied to separate the independent source components, followed by Fourier and time-frequency analysis. For quantitative EEG analysis, we apply several statistical complexity measures to the EEG signals and evaluate the differences between two groups of patients: the subjects in deep coma, and the subjects who were categorized as brain death. We report statistically significant differences of quantitative statistics with real-life EEG recordings in such a clinical study, and we also present interpretation and discussions on the preliminary experimental results.

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial

BackgroundCatheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.Methods and findingsWe investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (Nadir_HbO, i.e., lowest oxyhemoglobin concentration and Peak_HbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater Nadir_HbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater Peak_HbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher Peak_HbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher Nadir_HbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller Nadir_HbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller Peak_HbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.ConclusionsWe observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02703090","term_id":"NCT02703090"}}NCT02703090

In a randomized controlled trial, Keerthana Karunakaran, Barry Kussman, and colleagues study whether remifentanil attenuates pain-related brain activity during cardiac ablation surgery.     

Implementation of Neural Networks to Frontal Electroencephalography for the Identification of the Transition Responsiveness/Unresponsiveness During Induction of General Anesthesia

ObjectiveGeneral anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness (LOR) due to brainstem inactivation. Precise identification of the LOR during the induction of general anesthesia is extremely important to provide personalized information on anesthetic requirements and could help maintain an adequate level of anesthesia throughout surgery, ensuring safe and effective care and balancing the avoidance of intraoperative awareness and overdose. So, main objective of this paper was to investigate whether a Convolutional Neural Network (CNN) applied to bilateral frontal electroencephalography (EEG) dataset recorded from patients during opioid-propofol anesthetic procedures identified the exact moment of LOR.Material and methodsA clinical protocol was designed to allow for the characterization of different clinical endpoints throughout the transition to unresponsiveness. Fifty (50) patients were enrolled in the study and data from all was included in the final dataset analysis. While under a constant estimated effect-site concentration of 2.5 ng/mL of remifentanil, an 1% propofol infusion was started at 3.3 mL//h until LOR. The level of responsiveness was assessed by an anesthesiologist every six seconds using a modified version of the Richmond Agitation-Sedation Scale (aRASS). The frontal EEG was acquired using a bilateral bispectral (BIS VISTA™ v2.0, Medtronic, Ireland) sensor. EEG data was then split into 5-second epochs, and for each epoch, the anesthesiologist's classification was used to label it as responsiveness (no-LOR) or unresponsiveness (LOR). All 5-second epochs were then used as inputs for the CNN model to classify the untrained segment as no-LOR or LOR.ResultsThe CNN model was able to identify the transition from no-LOR to LOR successfully, achieving 97.90±0.07% accuracy on the cross-validation set.ConclusionThe obtained results showed that the proposed CNN model was quite efficient in the responsiveness/unresponsiveness classification. We consider our approach constitutes an additional technique to the current methods used in the daily clinical setting where LOR is identified by the loss of response to verbal commands or mechanical stimulus. We therefore hypothesized that automated EEG analysis could be a useful tool to detect the moment of LOR, especially using machine learning approaches.     

Coordinated expression in chronically unconscious persons.

The clinically described ''persistent vegetative state'' (PVS), consists of wakefulness unaccompanied by any evidence of the subject''s awareness of self or environment. Past studies from our own and other laboratories have used positron emission tomography (PET) to study brain metabolism in approximately 20 such patients during wakeful periods. All those efforts identified global cerebral glucose metabolism at or below levels encountered during deep barbiturate anaesthesia. Nevertheless, the clinical literature includes rare reports of relatively isolated cognitive functions expressed by PVS patients late in their course. The observation raises the question of whether such activity reflects awareness or unconscious automatic behaviour. We employed magnetometry (MEG), PET scanning, MR imaging and 24-hour EEG recordings to evaluate three patients clinically vegetative between six months and 20 years after onset. Neither meticulous clinical examinations nor 24-hour EEG and video monitoring provided any hint of cognitive interaction in any subject. Nevertheless, patient 1 uttered single words once every 48 hours or more; patient 2 frequently expressed coordinated, non-purposeful, non-dystonic movements in arms and/or legs; and, patient 3 expressed strong emotional negativity without motor responses to noxious stimuli with occasional quieting in response to prosodic stimuli. All patients had whole-brain averaged global metabolism levels below 50% of normal. Patient 1, however, demonstrated preserved islands of increased metabolism in the posterior frontal and posterior temporal lobes, as well as MEG activations of Heschl''s gyrus all located in the left hemisphere. In patient 2, selected increased metabolism was confined to the frontal poles and related subcortical structures. MRI in patient 3 demonstrated severe, bilateral post-traumatic cerebral atrophy. PET metabolism was diffusely reduced to 40% of normal but MEG evoked potentials indicated early and late sensory processing with abnormal later evoked components. The correlation of fragmentary behaviour with preserved metabolic and physiologic activity in cortical and subcortical regions known to support specific modular functions is novel. The finding demonstrates the capacity of severely damaged brains to partially express surviving modular functions without evidence of integrative processes that would be necessary to produce consciousness. We conclude that the mere expression of isolated neuropsychologic activity by isolated modules is insufficient to generate consciousness in overwhelmingly damaged brains.     

Identification of BDNF Sensitive Electrophysiological Markers of Synaptic Activity and Their Structural Correlates in Healthy Subjects Using a Genetic Approach Utilizing the Functional BDNF Val66Met Polymorphism

Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF) is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such “synaptogenic” therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load) on electrophysiological (EEG) markers of synaptic activity and their structural (MRI) correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met). Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN); and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left) prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early clinical development to examine target engagement or drug related efficacy of synaptic repair therapies in humans.     

咪达唑仑用于上肢创伤病人麻醉前给药的遗忘作用与脑电变化

目的:评价咪达唑仑用于上肢创伤病人行高位硬膜外阻滞的遗忘作用和相应的脑电变化。方法:选择40例单纯上肢创伤病人行高位硬膜外阻滞随机双盲分为四组:咪达唑仑0.15mg/kg和0.10mg/kg,安定0.20mg/kg,生理盐水2ml,麻醉前30分钟肌注,观察用药前后脑电改变,镇静分级对麻醉操作的遗忘率和程度以及术后心理状况。结果:用咪达唑仑后,镇静程度与遗忘效果有显著变化。0.10mg/kg咪达唑仑的遗忘率为70%,其中90%为不全遗忘;0.15mg/kg咪达唑仑可达到100%完全遗忘;咪达唑仑的脑电功率谱变化为δ和β相对功率明显增加,而θ和α相对功率明显下降。结论:肌注咪达唑仑完全可以消除病人对高位硬膜外麻醉穿刺操作过程的不良回忆,并与剂量相关。     

食物奖赏和渴求行为相关的大鼠左侧眶额叶皮质Delta频段脑电活动(英文）

眶额叶皮质与中脑边缘多巴胺奖赏系统有着复杂的相互纤维联系。先前的研究探讨了药物成瘾过程中眶额叶皮质的脑电活动。在本实验中,将探讨食物奖赏和渴求过程中该皮质的脑电活动。实验采用了两个环境:对照环境和食物刺激相关的环境。首先,训练大鼠在食物刺激相关的环境中吃巧克力花生豆,而后在该环境中设置两种不同的刺激方式:能看到和闻到但不能吃到(渴求实验),或者仍旧可以吃到巧克力花生豆(奖赏实验);同时进行左侧眶额叶皮质的脑电记录。结果发现,在食物刺激相关的环境中大鼠 Delta 频段(2-4 Hz)的脑电活动与食物刺激显著相关,此外,与在对照环境中相比,其相对功率在食物渴求时下降而在食物奖赏时升高。本实验表明,食物相关的奖励可以改变大鼠眶额叶皮质的脑电活动,而且,Delta 频段的脑电活动能够作为监测该奖励的一个指标。