# Mechanisms and Functions of Cortical Activity to Restore Behavior

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $487,477

## Abstract

Project Summary
Monitoring the transition to wakefulness is critical during restoration to consciousness after brain injury,
anesthesia, and in those COVID-19 survivors that have altered consciousness. However, we have an imprecise
understanding of neural dynamics linked to behavioral changes as subjects awaken. Our previous work
discovered that stimulating the anterior nucleus gigantocellularis (aNGC) promotes arousal from a coma-like
state. We proposed recruiting multiple arousal pathways through aNGC as an avenue to triggering widespread
activation resulting in wakefulness. Notably, aNGC activation increased frontal-motor cortical activity and
restored full mobility through modulation of an aNGC-to-frontal-motor-cortex pathway despite high anesthetic
concentration exposure. We also showed that animals emerging from diverse coma-like states share a common
dynamic process of cortical and motor arousal that can be consistently sequenced from deep to high arousal
levels. We identified five cortical periods that tracked restored motor behavior in a hypoglycemic coma and a
range of anesthetics, whether inhaled or injected, alongside conventional righting reflex assays. Based on these
findings, we postulate that restoring waking is a common progressive process in which cortical patterns contain
metrics of consciousness that distinguish reflexive from purposeful movements. We hypothesize that cortical
measurements that link neural responsiveness to defined behaviors are an applicable method that can
extend the analysis of the recovery of consciousness beyond monitoring reflexive movements.
Our proposal deepens our understanding of the contribution of cortical neural subtypes, the neuronal pathways
underlying aNGC-induced changes in frontal-motor cortical activity, and the temporal dynamics that distinguish
reflexive from the initiation of voluntary behaviors in our rodent-low arousal models. In addition, we will establish
the cortical patterns that unpack these behavioral transitions. Since pathological states of unconsciousness are
vastly heterogeneous, having a clear understanding of ordinary recovery serves to better appreciate the
variability imposed by the injury to cortical activity and behavior. Thus, we will identify how damaged neural
circuits affect established cortical activity pathways and dynamics that underlie behavior recovery. The proposed
studies are thus significant because they will establish the mechanistic correspondence, examining activation of
neural pathways and their dynamics linked to habitual and intentional behaviors that reveal novel, medically
relevant biomarkers that promote a robust inference of arousal states during emergence from anesthesia and
after brain injury.

## Key facts

- **NIH application ID:** 10874730
- **Project number:** 5R01NS129836-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Diany Paola Calderon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $487,477
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874730

## Citation

> US National Institutes of Health, RePORTER application 10874730, Mechanisms and Functions of Cortical Activity to Restore Behavior (5R01NS129836-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10874730. Licensed CC0.

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