Anesthesia Task Details

Anesthesia Task have five experiments:

• Anesthesia Experiments

  Ketamine and medetomidine (KtMd)

  Propofol (Pf)

  Ketamine (Kt)

  Medetomidine (Md)

• Natural Sleep Experiment (Slp)

Task Design:

• Anesthesia Experiments

• Natural Sleep Experiment

Detail Method:

• Anesthesia Experiment

We did 4 experiments in which the monkey was under anesthesia. Two anesthetic agents, ketamine and medetomidine, were used in the first experiment. In other experiments, only propofol, ketamine or medetomidine were used respectively.

During the experiments, the monkey was seated in a primate chair with both arms and head movement restricted. Neural data were acquired during the experiment. There were three conditions that were awake, anesthetized and recovery conditions. The awake condition had eyes-opened and eyes-closed conditions. At first monkey’s eyes were opened and the monkey sat calmly for up to 20 min. Next the monkey’s eyes were covered by an eye-mask to refrain from evoking visual response. During the eyes-closed condition, the monkey would sat calmly for up to 20 min at which time we would start to monitor heart rate.

In experiments where the ketamine-medetomidine cocktail was used to induce anesthesia, the ketamine (～5.0 mg/kg for M1–M3, 8.8 mg/kg for M4) and medetomidine (～0.016 mg/kg for M1–M3, 0.053 mg/kg for M4) were injected intramuscularly (see Table). In contrast, propofol-induced anesthesia was achieved through intravenous propofol (5.2 mg/kg for M1 and M2) injection (see Table). In ketamine-induced anesthesia experiment, the ketamine (~5.1 mg/kg for M1 and M2) was injected intramuscularly (see Table). In medetomidine-induced anesthesia experiment, the medetomidine (～0.018 mg/kg for M1 and M2) was injected intramuscularly (see Table). Loss of consciousness (LOC) was defined as the point at which a monkey no longer responded to manipulation of the monkey’s hand or touching of the nostril or philtrum with a cotton swab. As an additional confirmation that the monkey had achieved LOC, we could observe slow wave oscillations in the neural signal. After LOC was established, neural activity was recorded for ~25 min for the ketamine-medetomidine-induced anesthesia experiment, and ~10 min for the propofol-, ketamine-, and medetomidine-induced anesthesia experiments respectively (Anesthetized condition). Heart rate and breathing were monitored carefully throughout the length of the experiment.

After LOC, the monkey recovered from anesthesia (Recovery condition). In ketamine-medetomidine- and medetomidine-induced anesthesia experiments, atipamezole which is an antagonist of medetomidine was injected intramuscularly and the monkey recovered quickly after the injection. In propofol- and ketamine-induced anesthesia experiments, the monkey was left alone for the recovery condition. In the recovery condition, there were eyes-closed and eyes-opened conditions. The onset of eyes-closed condition in recovery condition was defined as the point at which the slow wave oscillation in the neural signal disappeared in ketamine-medetomidine- and medetomidine-induced anesthesia experiments, and the monkey started to respond to manipulation of the monkey’s hand or touching of the nostril or philtrum with a cotton swab in propofol- and ketamine-induced anesthesia experiments.

During eyes-closed condition, the monkey’s eyes were closed and the monkey sat calmly for about 15 min. Next the monkey’s eyes were opened by removing the eye-mask. During the eyes-opened condition, the monkey would sat calmly for about 15 min.

We performed two to three recording sessions for each monkey, all on separate days (See Table).

• Natural Sleep Experiment

Natural sleep experiment: During the sleep experiment under the conditions of sleep, awake with eyes closed, and awake with eyes open, the state of the monkey was monitored by recording electrooculogram (EOG) and electromyography (EMG) signals.

EOG and EMG were performed at a sampling rate of 1 kHz by a Cerebus data acquisition system (Blackrock Microsystems, Salt Lake City, UT, USA)). EOG signals were recorded from the muscles of the right eye by placing 2 electrodes (Nihon Kohden, Disposable electrode for ECG Monitoring M-150) on near the outer and inner canthi of the right eye. The difference in potential between the 2 electrodes was then used as the EOG signal. Two electrodes were put on the chin, and the difference in the potential between these electrodes was used as the EMG signal.

In the sleep condition, the eyes were covered by an eye mask, and the experimental room was kept quiet and dark for up to 1.5 hours. During this period, slow wave oscillation appeared intermittently in the ECoG signal. Immediately following the sleep condition, the light was turned on, and data acquisition was continued under the eyes closed condition for 10 minutes. The eye mask was removed for the eyes open condition, which lasted for 10 minutes. For monkeys M1 and M2, 3 and 4 recording sessions were performed on separate days, respectively (See Table). The sleep state was defined by the degree of spatial synchronization in slow wave oscillations (See Yanagawa 2013 for the detail method).