# General Anesthetics and Cerebral Cortical Sensory Integration

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $423,705

## Abstract

The overall goal of this project is to apply novel approaches to probe local neuronal activity in 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.
We propose 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. In all aims, we will use four drugs
representing four canonical pharmacological classes of anesthetics: desflurane, propofol, dexmedetomidine,
and ketamine to find a common, agent-invariant neuronal correlate of unconsciousness. The proposed project
builds upon our two decades-long integrative investigations 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 should augment our basic science knowledge that may lead, on the long
term, to the development of improved bedside-applicable monitoring of the state o...

## Key facts

- **NIH application ID:** 10369683
- **Project number:** 5R01GM056398-23
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Anthony George Hudetz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,705
- **Award type:** 5
- **Project period:** 1997-08-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369683

## Citation

> US National Institutes of Health, RePORTER application 10369683, General Anesthetics and Cerebral Cortical Sensory Integration (5R01GM056398-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10369683. Licensed CC0.

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