# Chronic sleep disruption as prognostic biomarker of cognitive recovery following traumatic brain injury.

> **NIH VA I21** · PHILADELPHIA VA MEDICAL CENTER · 2024 · —

## Abstract

Disrupted sleep is a common and persistent symptom after traumatic brain injury, which can significantly
complicate recovery. Memories are formed and encoded in the hippocampus and then consolidated via replay
during sleep. Consolidated memories are then transferred from the hippocampus to the cortex via synchronous
interaction between cortical sleep spindles and hippocampal sharp-wave ripple oscillations. Therefore, chronic
sleep disturbances may lead to memory dysfunction and induce adverse changes in cognitive performance over
time post-TBI. However, the mechanisms underlying cognitive deficits due to chronic sleep disruption following
traumatic brain injury remain poorly understood.
To improve quality of life in Service Members and Veterans with traumatic brain injury, an understanding of the
varied mechanisms triggered by traumatic brain injury is required to prevent or optimally manage cognitive
recovery over time post brain injury. Therefore, our long-term goal is to uncover fundamental principles of
cognitive deficits following brain trauma. Using in vivo electrophysiology, we demonstrated a significant reduction
in duration and depth of slow wave sleep as well as decrease in sleep spindles detected in the CCI-injured
cortex. Moreover, we also demonstrated significant changes in the hippocampal ripple oscillations, potentially
indicating loss of information encoded in the sharp-wave ripple oscillations post-CCI. These preliminary results,
together with histopathological changes observed in the hippocampus and cortex, have led to our central
hypothesis that TBI-induced sleep disturbances may contribute to cognitive dysfunction by disrupting the
memory reactivation loop between cortex and hippocampus.
The goal of this project is to interrogate chronic sleep disruption using a clinically relevant large animal model of
TBI. Our specific objective for this proposal is to determine a prognostic value of sleep spindles as a biomarker
for cognitive recovery following TBI. Our interdisciplinary team of the electrophysiologists and a trauma
neuropathologist is uniquely poised to address this fundamental question by combining our broad background
in swine in vivo electrophysiology, cognitive behavior, and histopathology. In this way, we will use our unique,
large animal model of CCI injury (swine) along with wireless video EEG monitoring and cognitive behavioral
testing to up to 6 months post-CCI injury to provide important insight into the mechanisms underlying the
persistent cognitive deficits post-TBI.
Our proposal directly addresses the Rehabilitation Research and Development (RR&D) Service mission to
restore brain function impaired by injury by pioneering research to maximize Veterans’ physical, psychological,
and social function. Examination of the circuit level changes in a clinically relevant large animal model, in parallel
with neuropathological outcome and cognitive testing, provides a powerful translational approach to
understanding a pro...

## Key facts

- **NIH application ID:** 10801930
- **Project number:** 1I21RX004629-01A1
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Alexandra V. Ulyanova
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801930

## Citation

> US National Institutes of Health, RePORTER application 10801930, Chronic sleep disruption as prognostic biomarker of cognitive recovery following traumatic brain injury. (1I21RX004629-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801930. Licensed CC0.

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