General Anesthetics and Cerebral Cortical Sensory Integration

The overall goal of this research project is to investigate local neuronal mechanisms in the cerebral cortex associated with complex, natural sensory experience and to determine how general anesthetics may alter sensory-specific contents of consciousness. Our general hypothesis is that anesthetic modulation of consciousness is closely tied to the modification of specific spatiotemporal patterns of neuronal activity in local cortical circuits. We will test our hypothesis in the rat visual and association cortex as a model system in vivo.

The project has three specific aims. In the first aim, we will use multineuronal recording with chronically implanted microelectrode arrays to determine stereotypic neuronal firing sequences that conform to moving visual stimuli presented by virtual reality projection while the subject is allowed run on a spherical treadmill along a virtual path.  We will examine how anesthetics at incremental doses may influence both spontaneous and visual stimulus-related firing sequences, comparing behaviorally defined conscious and unconscious states. We hypothesize that navigating virtual reality will induce reproducible spatiotemporal sequences of neuron ensembles and that sensory specificity of these sequences would be reduced by anesthetics particularly at a dose they produce observable signs of unconsciousness.

In the second aim, we will apply electrical microstimulation to elicit reproducible local network activity patterns and map the effective connectivity of neuronal networks. We hypothesize that input-specific multineuronal firing sequences will be stabilized by repeated stimulation, will be spontaneously replayed in the absence of stimulation as a result of network plasticity and that anesthesia will degrade but not necessarily abolish all stimulus-selective sequences.

In the third aim, multichannel recording and microstimulation will be combined with an adaptive artificial neuronal network model to create a closed-loop hybrid brain-to-brain assay of visual stimulus-specific information transfer between two virtual reality-embedded subjects. This will be a novel attempt to read out meaningful sensory neuronal information from a subject’s brain and transfer it to another subject as a task performance agent to use it for an assessment of the first subject’s state of consciousness.

This project builds upon our two decades-long investigation into the neuronal mechanisms of anesthesia at systems level. The work should advance our understanding of the neurobiological basis of consciousness and anesthesia.  The anticipated results will augment our basic science knowledge that may lead, on the long term, to the development of improved bedside-applicable monitoring of the state of consciousness during general anesthesia and in patients with disorders of consciousness. The results may also inspire new approaches to ameliorate deficits and replace or restore neural functions in patients with physical or mental disabilities.