Bruce MacIver

The Center of Consciousness; Neurophysiological Evidence For consideration as a Plenary talk in: PL-11: Altered States of Consciousness High Frequency (> 1.0 KHz) Signals in Frontal Cortex at Loss and Recovery of Consciousness M Bruce MacIver, Department of Anesthesiology, Perioperative and Pain Medicine, and The Neuroscience Institute, Stanford University, Stanford CA 94305 maciver@stanford.edu Introduction: Brain oscillations have rarely been studied at frequencies beyond 200 Hz, and it remains unknown what the highest frequency of brain bioelectric activity is. To study this, we used high frequency recording of oscillations when rats fell asleep and awakened. In addition, we used the volatile anesthetic, isoflurane, to depress activity at behavioral endpoints of loss of righting reflex (LORR) and loss tail clamp responses (LOTC). These endpoints provided surrogate measures of loss of consciousness (LORR) and surgical anesthesia (LOTC) in rats. We recorded signals from DC to 20KHz; extending analysis of oscillatory cortical activity well beyond traditional frequency ranges. Methods: Local field potentials were recorded from layer 2/3 of frontal cortex in rats using chronically implanted electrodes. Custom amplifiers and analysis were used to measure potentials recorded and digitized at 20 KHz frequencies. Rats were placed in an air-tight chamber with a controlled atmosphere of room air and recorded as animals went to sleep and awoke. For comparison, we also studied loss and recovery of consciousness induced by anesthesia, where room air was slowly replaced with increasing concentrations of isoflurane in oxygen, delivered from a calibrated vaporizer. Animal behavior and physiology were carefully monitored to ensure body temperature remained constant and to determine LORR and LOTC responses. Rats recovered following each experiment after awakening from natural sleep or upon replacing isoflurane/O2 with room air. Results: Both natural sleep and isoflurane produced a characteristic profile of effects, consistent with previous reports. At LORR high amplitude slow wave activity was evident, similar to but with lower gamma frequencies than seen in natural slow-wave (delta) sleep, this transitioned to a burst suppression pattern at LOTC. Spectral analysis revealed that increased slow wave activity was accompanied by decreased higher frequencies in the gamma, high-gamma bands, as previously reported, and extending to >1.0 KHz at LORR. We tested whether this high frequency activity was due to action potential discharge recorded from neurons near the electrode tip and found that it was not. High frequency activity also did not appear to be harmonics from lower frequency oscillations, since the power decay was smooth, not peaked like for harmonics. Discussion: Sleep and isoflurane depressed high frequency cortical activity well beyond the traditional EEG frequency range of 200 Hz. Our presentation will discuss brain processes that could be associated with this high frequency brain activity, between 300 and 1200 Hz, including: molecular (NMDA proteins, microtubules, K channels, etc.), synaptic (decreased glutamate, increased GABA) and circuit level (decreased complexity) targets that contribute to loss of consciousness. Key words: Sleep, Anesthetic, EEG, Cortex, Unconscious, High-gamma, high frequency brain activity.

My biographic info is at:

https://profiles.stanford.edu/m-maciver