Moira L. Steyn-Ross

The Bispectral Index: A Measure of Depth of Sleep?

UNLABELLED How does physiological sleep affect the Bispectral Index (BIS)? We collected electroencephalographic (EEG) data from five subjects during the early part of the night, comparing the changes in the BIS with the conventional EEG stages of sleep. We found that the BIS was a consistent marker of depth of sleep. Light sleep occurred at BIS values of 75-90, slow-wave sleep occurred at BIS values of 20-70, and rapid eye movement sleep occurred at BIS values of 75-92. The effects of natural sleep on the BIS seem to be similar to the effects of general anesthesia on the BIS. The BIS may have a role in monitoring depth of sleep. IMPLICATIONS Electroencephalographic data were collected from five subjects during sleep. We found that the Bispectral Index decreased during increasing depth of sleep in a fashion very similar to the decrease in Bispectral Index that occurs during general anesthesia. This study further highlights the electroencephalographic similarities of states of sleep and general anesthesia.

Cortical entropy changes with general anaesthesia: theory and experiment

Commonly used general anaesthetics cause a decrease in the spectral entropy of the electroencephalogram as the patient transits from the conscious to the unconscious state. Although the spectral entropy is a configurational entropy, it is plausible that the spectral entropy may be acting as a reliable indicator of real changes in cortical neuronal interactions. Using a mean field theory, the activity of the cerebral cortex may be modelled as fluctuations in mean soma potential around equilibrium states. In the adiabatic limit, the stochastic differential equations take the form of an Ornstein-Uhlenbeck process. It can be shown that spectral entropy is a logarithmic measure of the rate of synaptic interaction. This model predicts that the spectral entropy should decrease abruptly from values approximately 1.0 to values of approximately 0.7 as the patient becomes unconscious during induction of general anaesthesia, and then not decrease significantly on further deepening of anaesthesia. These predictions were compared with experimental results in which electrocorticograms and brain concentrations of propofol were recorded in seven sheep during induction of anaesthesia with intravenous propofol. The observed changes in spectral entropy agreed with the theoretical predictions. We conclude that spectral entropy may be a sensitive monitor of the consciousness-unconsciousness transition, rather than a progressive indicator of anaesthetic drug effect.

The sleep cycle modelled as a cortical phase transition.

We present a mean-field model of the cortex that attempts to describe the gross changes in brain electrical activity for the cycles of natural sleep. We incorporate within the model two major sleep modulatory effects: slow changes in both synaptic efficiency and in neuron resting voltage caused by the ∼90-min cycling in acetylcholine, together with even slower changes in resting voltage caused by gradual elimination during sleep of somnogens (fatigue agents) such as adenosine. We argue that the change from slow-wave sleep (SWS) to rapid-eye-movement (REM) sleep can be understood as a first-order phase transition from a low-firing, coherent state to a high-firing, desychronized cortical state. We show that the model predictions for changes in EEG power, spectral distribution, and correlation time at the SWS-to-REM transition are consistent not only with those observed in clinical recordings of a sleeping human subject, but also with the on-cortex EEG patterns recently reported by Destexhe et al. [J. Neurosci.19(11), (1999) 4595–4608] for the sleeping cat.

General Anesthetic-induced Seizures Can Be Explained by a Mean-field Model of Cortical Dynamics

GENERAL anesthesia is a state in which cerebral activity is usually profoundly suppressed. It is paradoxical that some general anesthetic agents—drugs whose primary action is to decrease central nervous system activity and that have been widely used to treat seizures—can also provoke cortical seizures when the patient is deeply anesthetized. Traditionally, the explanation for this phenomenon has been sought at a molecular or synaptic level of description, by finding differences between general anesthetic drugs that commonly precipitate seizure activity and those drugs that do not cause seizures. It has been suggested that proconvulsant drugs (such as enflurane) may (1) act to decrease the amplitude of miniature inhibitory postsynaptic currents or (2) elicit greater calcium-induced presynaptic mobilization of excitatory neurotransmitters than anticonvulsant drugs (such as isoflurane or thiopentone). These descriptions are qualitative. Are these observations of true causative mechanisms of seizure genesis, or are they simply observations of epiphenomena? It is not clear exactly how these observations at synaptic and molecular scales would quantitatively result in repetitive synchronous widespread burst firing of cortical neurons—the signature of seizure activity. In this article, we describe a mathematical model of cerebral cortical function (the so-called mean-field model). In our model, we are able to input the known molecular-scale effects of anesthetic drugs and see how they alter the output (a “pseudoencephalogram”) of the computer-simulated “pseudocortex.” We incorporate the values of inhibitory postsynaptic potential (IPSP) amplitude and duration that have been previously published and studied in detail for isoflurane and enflurane, and we compare the output from simulations run on our theoretical mathematical model with various experimental and clinical observations that have been previously reported in the scientific literature. We find that subtle changes in the shape of the IPSP—induced by enflurane—are sufficient to cause the model of the cerebral cortex to undergo a sudden change in behavior from a general anesthetic state (in which neuronal firing is suppressed) into a seizure-like state—manifest as oscillation between neuronal silence and supramaximal neuronal firing. We use the example of enflurane-induced seizures as a dramatic demonstration of the application of mean-field models of cortical dynamics to link molecular and macroscopic descriptions of nervous system phenomena.

The K-complex and slow oscillation in terms of a mean-field cortical model

We use a mean-field macrocolumn model of the cerebral cortex to offer an interpretation of the K-complex of the electroencephalogram to complement those of more detailed neuron-by-neuron models. We interpret the K-complex as a momentary excursion of the cortex from a stable low-firing state to an unstable high-firing state, and hypothesize that the related slow oscillation can be considered as the periodic oscillation between two meta-stable solutions of the mean-field model. By incorporating a Hebbian-style learning rule that links the growth in synapse strength to fluctuations in soma potential, we demonstrate a self-organization behaviour that draws the modelled cortex close to the edge of stability of the low-firing state. Furthermore, a very slow oscillation can occur in the excitability of the cortex that has similarities with the infra-slow oscillation of sleep.

Connexin36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors

OBJECTIVE Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model. METHODS Mice (2-3months old) with Cx36 wildtype (WT) or Cx36KO genotype were treated with vehicle or 10-40mg/kg of the convulsant PTZ by intraperitoneal injection. Seizure and seizure-like behaviors were scored by examination of video collected for 20min. Quantitative real-time PCR (QPCR) was performed to measure potential compensatory neuronal connexin (Cx30.2, Cx37, Cx43 and Cx45), pannexin (PANX1 and PANX2) and gamma-aminobutyric acid type A (GABA(A)) receptor α1 subunit gene expression. RESULTS Cx36KO animals exhibited considerably more severe seizures; 40mg/kg of PTZ caused severe generalized (≥grade III) seizures in 78% of KO, but just 5% of WT mice. A lower dose of PTZ (20mg/kg) induced grade II seizure-like behaviors in 40% KO vs. 0% of WT animals. There was no significant difference in either connexin, pannexin or GABA(A) α1 gene expression between WT and KO animals. CONCLUSION Increased sensitivity of Cx36KO animals to PTZ-induced seizure suggests that Cx36 gap junctional communication functions as a physiological anti-convulsant mechanism, and identifies the Cx36 gap junction as a potential therapeutic target in epilepsy.

Estimating Biomass for New Zealand Pasture Using Optical Remote Sensing Techniques

Abstract One essential requirement for an increase in the efficiency of pastoral grazing management in New Zealand is the development of a quick, reliable, and objective method for assessing pasture bulk. The traditional method for estimating biomass entails harvesting and dry‐weighing sample quadrats, then extrapolating from the sample to the paddock. This is labour‐intensive and slow, so we seek a means of ‘remote weighing’ of the pasture using optical remote sensing techniques. Field trials in the Waikato region (latitude 38°S) of New Zealand have demonstrated that measuring pasture reflectance in three wavelength bands (near‐infrared, red, green) permits us to retrieve green biomass to within an average root-mean square error of 260 kg / ha, for pasture green‐bulk ranging from 70 to 4000 kg / ha, using a three‐band regression. We find that the usual remote measure of greenness, NDVI (normalized difference vegetation index), saturates at moderate pasture densities, so is not useful in the New Zealand p...

Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex

During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state might be an indication of failure to form coherent neuronal assemblies necessary for consciousness. A generalized seizure event is a pathological brain state that is the clearest manifestation of waves of synchronized neuronal activity. Since gap junctions provide a direct electrical connection between adjoining neurons, thus enhancing synchronous behavior, reducing gap-junction conductance should suppress seizures; however there is no clear experimental evidence for this. Here we report theoretical predictions for a physiologically-based cortical model that describes the general anesthetic phase transition from consciousness to coma, and includes both chemical synaptic and direct electrotonic synapses. The model dynamics exhibits both Hopf (temporal) and Turing (spatial) instabilities; the Hopf instability corresponds to the slow (≲8 Hz) oscillatory states similar to those seen in slow-wave sleep, general anesthesia, and seizures. We argue that a delicately balanced interplay between Hopf and Turing modes provides a canonical mechanism for the default non-cognitive rest state of the brain. We show that the Turing mode, set by gap-junction diffusion, is generally protective against entering oscillatory modes; and that weakening the Turing mode by reducing gap conduction can release an uncontrolled Hopf oscillation and hence an increased propensity for seizure and simultaneously an increased sensitivity to GABAergic anesthesia.

The electrocortical effects of enflurane: experiment and theory.

BACKGROUND: High concentrations of enflurane will induce a characteristic electroencephalogram pattern consisting of periods of suppression alternating with large short paroxysmal epileptiform discharges (PEDs). In this study, we compared a theoretical computer model of this activity with real local field potential (LFP) data obtained from anesthetized rats. METHODS: After implantation of a high-density 8 × 8 electrode array in the visual cortex, the patterns of LFP and multiunit spike activity were recorded in rats during 0.5, 1.0, 1.5, and 2.0 minimum alveolar anesthetic concentration (MAC) enflurane anesthesia. These recordings were compared with computer simulations from a mean field model of neocortical dynamics. The neuronal effect of increasing enflurane concentration was simulated by prolonging the decay time constant of the inhibitory postsynaptic potential (IPSP). The amplitude of the excitatory postsynaptic potential (EPSP) was modulated, inverse to the neocortical firing rate. RESULTS: In the anesthetized rats, increasing enflurane concentrations consistently caused the appearance of suppression pattern (>1.5 MAC) in the LFP recordings. The mean rate of multiunit spike activity decreased from 2.54/s (0.5 MAC) to 0.19/s (2.0 MAC). At high MAC, the majority of the multiunit action potential events became synchronous with the PED. In the theoretical model, prolongation of the IPSP decay time and activity-dependent EPSP modulation resulted in output that was similar in morphology to that obtained from the experimental data. The propensity for rhythmic seizure-like activity in the model could be determined by analysis of the eigenvalues of the equations. CONCLUSION: It is possible to use a mean field theory of neocortical dynamics to replicate the PED pattern observed in LFPs in rats under enflurane anesthesia. This pattern requires a combination of a moderately increased total area under the IPSP, prolonged IPSP decay time, and also activity-dependent modulation of EPSP amplitude.

Frontal-Temporal Synchronization of EEG Signals Quantified by Order Patterns Cross Recurrence Analysis During Propofol Anesthesia

Characterizing brain dynamics during anesthesia is a main current challenge in anesthesia study. Several single channel electroencephalogram (EEG)-based commercial monitors like the Bispectral index (BIS) have suggested to examine EEG signal. But, the BIS index has obtained numerous critiques. In this study, we evaluate the concentration-dependent effect of the propofol on long-range frontal-temporal synchronization of EEG signals collected from eight subjects during a controlled induction and recovery design. We used order patterns cross recurrence plot and provide an index named order pattern laminarity (OPL) to assess changes in neuronal synchronization as the mechanism forming the foundation of conscious perception. The prediction probability of 0.9 and 0.84 for OPL and BIS specified that the OPL index correlated more strongly with effect-site propofol concentration. Also, our new index makes faster reaction to transients in EEG recordings based on pharmacokinetic and pharmacodynamic model parameters and demonstrates less variability at the point of loss of consciousness (standard deviation of 0.04 for OPL compared with 0.09 for BIS index). The result show that the OPL index can estimate anesthetic state of patient more efficiently than the BIS index in lightly sedated state with more tolerant of artifacts.