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

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

1011-116 Myocardial Rb Extraction Fraction: Determination in Humans

Ouantitation of myocardial blood flow (MBF) with diffusion-limited radiotracers as 82Rb and positron emission tomography (PET) requires knowledge of flow dependence of myocardial 82Rb extraction fraction. To determine this dependence we evaluated 7 patients (mean age (61.0±9.7) years, 4 males, 3 females) who had undergone coronary angiography with exclusion of relevant coronary stenoses and normal left ventricular function. 82Rb-PET clearance was simultaneously assessed with global MBF by the argon (Ar) inert gas method. 82Rb clearance was dynamically measured by a CTI-Siemens ECAT 931-08-12 scanner after i.v. injection of 1–1.2 GBq 82Rb. Ar gas desaturation was obtained by simultaneous arterial and coronary sinus blood sampling. Measurements were performed at rest and during vasodilatation induced by i.v. dipyridamole (0.7mg/kg/4min). Mean 82Rb clearance and Ar flow values were (0.39±0,03)ml/g/min and (0.69±0.14)ml/g/min at rest, respectively, and (0.47±0.09)ml/g/min and (1.48±0.49)ml/g/min during hyperemia. A fit with a two compartment model yielded E=PS/(PS+MBF) with PS=(0.82±0.09)ml/g/min (PS: permeability surface area product). These data (figure) provide for the best of our knowledge the first measured 82Rb extraction fraction in humans and may form the basis for more accurate quantitation of myocardial blood flow with 82Rb-PET

Anaesthesia Monitoring by Recurrence Quantification Analysis of EEG Data

Appropriate monitoring of the depth of anaesthesia is crucial to prevent deleterious effects of insufficient anaesthesia on surgical patients. Since cardiovascular parameters and motor response testing may fail to display awareness during surgery, attempts are made to utilise alterations in brain activity as reliable markers of the anaesthetic state. Here we present a novel, promising approach for anaesthesia monitoring, basing on recurrence quantification analysis (RQA) of EEG recordings. This nonlinear time series analysis technique separates consciousness from unconsciousness during both remifentanil/sevoflurane and remifentanil/propofol anaesthesia with an overall prediction probability of more than 85%, when applied to spontaneous one-channel EEG activity in surgical patients

Low Dose Isoflurane Exerts Opposing Effects on Neuronal Network Excitability in Neocortex and Hippocampus

The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity

Time delay of the qCON monitor and its performance during state transitions

We investigated the performance of the qCON index regarding its time delay for sudden changes in the anesthetic level as well as to separate responsiveness from unresponsiveness during loss and return of responsiveness (LOR and ROR). For evaluation of the time delay, we replayed relevant EEG episodes to the qCON to simulate sudden changes between the states (i) awake/sedation, (ii) adequate anesthesia, or (iii) suppression. We also replayed EEG from 40 patients during LOR and ROR to evaluate the qCON's ability to separate responsiveness from unresponsiveness. The time delays depended on the type of transition. The delays for the important transition between awake/sedation and adequate anesthesia were 21(5) s from awake/sedation to adequate anesthesia and 26(5) s in the other direction. The performance of the qCON to separate responsiveness from unresponsiveness depended on signal quality, the investigation window, i.e. ± 30 s or ± 60 s around LOR/ROR, and the specific transition being tested. AUC was 0.63-0.90 for LOR and 0.61-0.79 for ROR. Time delay and performance during state transitions of the qCON were similar to other monitoring systems such as bispectral index. The better performance of qCON during LOR than ROR probably reflects the sudden change in EEG activity during LOR and the more heterogeneous EEG during ROR