Cross-approximate entropy of cortical local field potentials quantifies effects of anesthesia - a pilot study in rats

<p>Abstract</p> <p>Background</p> <p>Anesthetics dose-dependently shift electroencephalographic (EEG) activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. Additionally, they uncouple brain areas in higher (gamma) frequency ranges possibly underlying conscious perception. It is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. But what happens at the local network level? Local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. As anesthetics bias cortical networks towards inhibition, we hypothesized that they may cause excessive synchrony and compromise information processing already on a small spatial scale. Using a recently introduced measure of signal independence, cross-approximate entropy (XApEn), we investigated to what degree anesthetics synchronized local cortical network activity. We recorded local field potentials (LFP) from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control (awake state) with those at increasing concentrations of isoflurane, enflurane and halothane.</p> <p>Results</p> <p>Cortical LFP signals were more synchronous, as expressed by XApEn, in the presence of anesthetics. Specifically, XApEn was a monotonously declining function of anesthetic concentration. Isoflurane and enflurane were indistinguishable; at a concentration of 1 MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimuli in 50% of subjects) both volatile agents reduced XApEn by about 70%, whereas halothane was less potent (50% reduction).</p> <p>Conclusions</p> <p>The results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of XApEn has a similar discriminatory power as changes of spontaneous action potential rates. Thus, XApEn of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain.</p

EEG responses to standardised noxious stimulation during clinical anaesthesia: a pilot study.

BACKGROUND During clinical anaesthesia, the administration of analgesics mostly relies on empirical knowledge and observation of the patient's reactions to noxious stimuli. Previous studies in healthy volunteers under controlled conditions revealed EEG activity in response to standardised nociceptive stimuli even at high doses of remifentanil and propofol. This pilot study aims to investigate the feasibility of using these standardised nociceptive stimuli in routine clinical practice. METHODS We studied 17 patients undergoing orthopaedic trauma surgery under general anaesthesia. We evaluated if the EEG could track standardised noxious phase-locked electrical stimulation and tetanic stimulation, a time-locked surrogate for incisional pain, before, during, and after the induction of general anaesthesia. Subsequently, we analysed the effect of tetanic stimulation on the surgical pleth index as a peripheral, vegetative, nociceptive marker. RESULTS We found that the phase-locked evoked potentials after noxious electrical stimulation vanished after the administration of propofol, but not at low concentrations of remifentanil. After noxious tetanic stimulation under general anaesthesia, there were no consistent spectral changes in the EEG, but the vegetative response in the surgical pleth index was statistically significant (Hedges' g effect size 0.32 [95% confidence interval 0.12-0.77], P=0.035). CONCLUSION Our standardised nociceptive stimuli are not optimised for obtaining consistent EEG responses in patients during clinical anaesthesia. To validate and sufficiently reproduce EEG-based standardised stimulation as a marker for nociception in clinical anaesthesia, other pain models or stimulation settings might be required to transfer preclinical studies into clinical practice. CLINICAL TRIAL REGISTRATION DRKS00017829

A mobile phone based alarm system for supervising vital parameters in free moving rats

Background: Study protocols involving experimental animals often require the monitoring of different parameters not only in anesthetized, but also in free moving animals. Most animal research involves small rodents, in which continuously monitoring parameters such as temperature and heart rate is very stressful for the awake animals or simply not possible. Aim of the underlying study was to monitor heart rate, temperature and activity and to assess inflammation in the heart, lungs, liver and kidney in the early postoperative phase after experimental cardiopulmonary bypass involving 45 min of deep hypothermic circulatory arrest in rats. Besides continuous monitoring of heart rate, temperature and behavioural activity, the main focus was on avoiding uncontrolled death of an animal in the early postoperative phase in order to harvest relevant organs before autolysis would render them unsuitable for the assessment of inflammation. Findings: We therefore set up a telemetry-based system (Data Science International, DSI™) that continuously monitored the rat’s temperature, heart rate and activity in their cages. The data collection using telemetry was combined with an analysis software (Microsoft excel™), a webmail application (GMX) and a text message-service. Whenever an animal’s heart rate dropped below the pre-defined threshold of 150 beats per minute (bpm), a notification in the form of a text message was automatically sent to the experimenter’s mobile phone. With

Poly-acrylic Acid Brushes and Adsorbed Proteins

Planar polyelectrolyte brushes are prepared by Langmuir-Schaefer based grafting of perdeuterated (styrene)49-b-(acrylic acid)222 block copolymer (dPS-b-PAA) to dPS pre-coated silicon supports with grafting density σPAA from 0.07 to 0.11 nm-2. The structure of the solvent-swollen brushes, i. e. the volume fraction profile of polymer segments, ϕPAA, as a function of altitude z from the grafting plane into the liquid phase is extracted from neutron reflectivity measurements. We find that for all cases investigated ϕPAA(z) resembles a Gaussian profile. Although very condensed, the PAA brushes can be loaded with bovine serum albumin (BSA). The integral amount of adsorbed BSA scales linearly with grafting density. We compare our z-resolved volume fraction profile ϕBSA(z) of BSA on PAA brushes with existing literature on that system. It is found that a cross-over takes place in the adsorption scheme from ternary compressive, where proteins can approach the grafting surface only by compressing the brush, to ternary insertive, where proteins enter the brush with only local perturbation of the concentration profile, as a function of RP/Hmax, where RP is the Stokes-Radius of the protein, and Hmax is the experimentally determined maximum height of the brush

A Product Formula for the Normalized Volume of Free Sums of Lattice Polytopes

The free sum is a basic geometric operation among convex polytopes. This note focuses on the relationship between the normalized volume of the free sum and that of the summands. In particular, we show that the normalized volume of the free sum of full dimensional polytopes is precisely the product of the normalized volumes of the summands.Comment: Published in the proceedings of 2017 Southern Regional Algebra Conferenc

The impact of tethered recording techniques on activity and sleep patterns in rats

Funding Information: The project was supported by grants of Deutsche Forschungsgemeinschaft (FOR 2591, GZ: PO681/9-1 and 9-2). The authors thank Sarah Glisic, Helen Stirling, Claudia Siegl, Sieglinde Fischlein, Andreas Kutschka and Isabella Waclawczyk for their excellent technical assistance. The authors thank Helen Stirling for language revision. Open Access funding enabled and organized by Projekt DEALPeer reviewedPublisher PD

Permutation entropy is not an age-independent parameter for EEG-based anesthesia monitoring.

BACKGROUND An optimized anesthesia monitoring using electroencephalographic (EEG) information in the elderly could help to reduce the incidence of postoperative complications. Processed EEG information that is available to the anesthesiologist is affected by the age-induced changes of the raw EEG. While most of these methods indicate a "more awake" patient with age, the permutation entropy (PeEn) has been proposed as an age-independent measure. In this article, we show that PeEn is also influenced by age, independent of parameter settings. METHODS We retrospectively analyzed the EEG of more than 300 patients, recorded during steady state anesthesia without stimulation, and calculated the PeEn for different embedding dimensions m that was applied to the EEG filtered to a wide variety of frequency ranges. We constructed linear models to evaluate the relationship between age and PeEn. To compare our results to published studies, we also performed a stepwise dichotomization and used non-parametric tests and effect sizes for pairwise comparisons. RESULTS We found a significant influence of age on PeEn for all settings except for narrow band EEG activity. The analysis of the dichotomized data also revealed significant differences between old and young patients for the PeEn settings used in published studies. CONCLUSION Based on our findings, we could show the influence of age on PeEn. This result was independent of parameter, sample rate, and filter settings. Hence, age should be taken into consideration when using PeEn to monitor patient EEG

Feeding of the probiotic bacterium Enterococcus faecium NCIMB 10415 differentially affects shedding of enteric viruses in pigs

Effects of probiotic bacteria on viral infections have been described previously. Here, two groups of sows and their piglets were fed with or without feed supplementation of the probiotic bacterium Enterococcus faecium NCIMB 10415. Shedding of enteric viruses naturally occurring in these pigs was analyzed by quantitative real-time RT-PCR. No differences between the groups were recorded for hepatitis E virus, encephalomyocarditis virus and norovirus. In contrast, astrovirus was exclusively detected in the non-supplemented control group. Rotavirus was shedded later and with lower amounts in the probiotic piglet group (p < 0.05); rotavirus-shedding piglets gained less weight than non-infected animals (p < 0.05). Serum titres of anti-rotavirus IgA and IgG antibodies were higher in piglets from the control group, whereas no difference was detected between sow groups. Phenotype analysis of immune cell antigens revealed significant differences of the CD4 and CD8β (p < 0.05) as well as CD8α and CD25 (p < 0.1) T cell populations of the probiotic supplemented group compared to the non-supplemented control group. In addition, differences were evident for CD21/MHCII-positive (p < 0.05) and IgM- positive (p < 0.1) B cell populations. The results indicate that probiotic bacteria could have effects on virus shedding in naturally infected pigs, which depend on the virus type. These effects seem to be caused by immunological changes; however, the distinct mechanism of action remains to be elucidated