Study On The Monitoring Of Anesthesia Effect Based On Auditory Response Time

Anesthetic is essential in clinical and animal studies. The use of anesthetics in the clinical work in order to protect patient safety and smooth operation. In animal experiments, the anesthetic to meet the need for operation and safety of researchers and experimental animals. In these two processes, the correct assessment of the anesthetic effect, that is, to accurately monitor the depth of anesthesia is very necessary. Currently what plays a dominant role by monitoring the cerebral cortex activity to monitor depth of anesthesia is EEG signal. However, many studies have found that this signal has drug differences, lack of timeliness, and accuracy and reliability to be improved.Auditory system as a model to study the anesthesia monitoring has its own superiority. Most neurons of the auditory pathway discharge spikes locked to the onset of an acoustic stimulus and maintained a sober state of alterniss to the outside world even in the state of anesthesia, coma, sleep and other state. And acoustic stimuli is not only simple and easy to control, but also can be combined into a variety of simple and complex stimulus conditions in the laboratory. In up to eight hearing levels. the inferior colliculus is a very important information integration center, which has an important role in the ascending and descending auditory pathways. Especially taking into account the experimental method, the inferior colliculus has been a information carrier in a lot of auditory researches.Encoding of sensory stimuli by the timing of neural discharges in central nervous system has received more and more agreements. The timing of spikes, especially the first spike latency may carry a lot of sensory information, causing more and more attention. The evidences have been uncovered in several systems such as visual, somatosensory, olfactory, hippocampus and auditory, in which the sensory representation is coded by timing of neural discharges. Anesthesia process generally takes a long recording time, so we have chosen local auditory evoked potential, which has the same spatial and temporal characteristics to single action potentials, as a research object, to study the changes of the evoked potential under anesthesia.Urethane is often used as an anesthetic because of its favourable anesthetic effect in auditory research. Animal model of this experiment is based on urethane anesthesia to change the state of the nervous system of mice, and we observed continuous changes of auditory evoked local potential during anesthesia to study the impact of the urethane, aimed at finding a more suitable indicators for monitoring the depth of anesthesia.In our study, extracellular recordings were made with metal micropipettes in inferior colliculus of mice to achieve responses to sound stimulation under anesthesia. A length of about1.5cm nails was glued to the dorsal surface of mouse skull with dental cement. Exposing the inferior colliculus, and thereafter the third day the awake mouse would be fixed in polyethylene-foam body mold, which was set in a flat-bottomed plate full of water. The plate was placed on a anti-vibration table in a sound-proof room. Pure tone bursts were used as acoustic stimuli and were generated and delivered using a Tucker-Davis Technologies System3. The tone burst signals lasting50ms each with a5ms rise-fall time. Pure tone bursts were played back using a computer with Brainware software which controlled the frequency and amplitude of pure tone bursts either manually or automatically.Results was collected and analysised with TDT3. The CF was first measured approximately by manually varying the frequency and amplitude of tone bursts after an IC neuron was isolated with noise stimulation. Then, the animals was injected with urethane, the stimulus conditions replaced the corresponding frequency-intensity combination. The waveforms were collected and stored as data sets. The data were monitored with respect to post-stimulus time histograms(PSTH) using Brain ware. Based on these data, the relationship between latency or amplitude and time was ploted, and fitting analysis of the corresponding coefficient of variation were plotted as functions of latency in offline processing.During the experiment, we continuously recorded the responses of inferior colliculus in13mice under different intensity levels. The recording session was divided into three stages:the first phase is to find the suitable neurons; the second phase is to determine the best frequency of the corresponding neurons; the third phase is to record the waveforms of auditory evoked potential every10minutes from the moment of completion of urethane injection. Matlab software platform is used to identify the latency and amplitude of evoked potentials under each stimulus condition. And comparison is made between latency and amplitude with time.After intraperitoneal administration of anesthetics, drug concentration of blood would gradually change because of anesthetic diffusion, uptake and metabolism This process may vary between mice due to reasons such as the mouse’s physique, but the general process is always the same. Our results show that, in this process, the latency of auditory local evoked potential changed in a identical way in different animals under stimuli of different intensities. While the amplitude function is more complex. Therefore, we qualitatively believe that latency of auditory evoked potential is a better indicator to described anesthesia depth. Further analysis was completed by Poincare plot. The scatter of the results can be carried out from two aspects:the aera of these points covered and the form of gathered. We study latency and amplitude of23recordings. The results show that, the area of latency was small, and the form was regular, illustrating the latency itself correlated well with the time. While the amplitude point covered a larger area, and gathered randomly, illustrating amplitude had no clear change rule. Further quantitative analysis were carried out to affirm that latency of auditory evoked potential was suitable as a index to indicate the depth of anaesthesia.Have selected indicator, we describe the changes in the depth of anesthesia with the indicator. We study the dependency the latency of the coefficient of variation on the recording time. The results showed that the CV period of2h was almost stable after the injection was finished2hours. Then the recording was divided into three parts:the accumulation, the stabilization and the period regain consciousness. This process was carried out by fitting method combined with the real experimental observations. And then we compared the duration of stabilization and consciousness. The stabilization was longer, indicating that the latency was to maintain a constant in a particular period of time when the urethane an anesthetic.We know that anesthetics act on the nervous system in the body leading to the changes of drug concentration of blood, and then the anesthesia was produced. Generally after administration of anesthetics, the concentration first gradually increased the maximum and then began to decreased, that is,the degree of inhibition of anesthetics on the nervous system gradually reaches its maximum and then began a slow recovery process. This results of this article was completely different. The latency of urethane reduced after the injection completed within2h, and then tends to be relatively stable and unchanged, until the animals were awake.Urethane as an anesthetic mainly inhibites the activity of acetylcholinesterase, resulting in the accumulation of acetylcholine. then normal nerve conduction of animals was affected. So changes of latency of urethane-induced may be derived from the conduction delay of the nerve fibers. As for the experimental results,that the changes in plasma concentration under urethane anesthesia is completely incompatible, we believe that this result was related with the effect of urethane on the blood glucose level.In discussing the effect urethane role, we also doubt whether the results shown was their own characteristics of the inferior colliculus. Based on the characteristics of frequency topology organizations of the inferior colliculus, we considered the location of groups of neurons recouded and the corresponding changes of their latency. The results confirmed the effect of urethane on the inferior colliculus is common, nothing to do with the location of neuron groups.Our results suggest that:the latency of the local potential as the indicator of anesthesia depth in the case of the urethane is reasonable, and the result that the period of latency was relatively stable within some time implied urethane could be anesthesia in other time-related hearing research.