# Mechanisms of Cognitive Impairment Following Early-Life Seizures

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $376,680

## Abstract

Project Summary
Epilepsy is a complex disorder which involves much more than seizures. As emphasized by the National
Academy of Science-sponsored Committee on the Public Health Dimensions of the Epilepsies,1 epilepsy may
be accompanied by a range of associated co-morbid health conditions that can have significant health and
quality of life implications. Of these comorbidities, cognitive impairment is one of the most common and
distressing aspects of epilepsy. Because the risk of cognitive impairment is greatest in young children, the
educational, vocational, social and economic implications are enormous. Remarkably, there are only a handful
of laboratories attempting to understand the pathophysiological basis of cognitive disturbances in early-life
seizures (ELS). It is the view of our laboratory that prior to preventing, limiting and reversing cognitive
comorbidities, it is essential to understand the neurobiological basis of developmental cognitive dysfunction
associated with ELS. One of the major difficulties in decoding the complex issue of cognitive outcomes
following ELS in children is the gulf between the behavioral/mental spheres in which these deficits are
substantiated and the underlying physiological/developmental domains that are both the cause of these deficits
and the most likely domains for therapy and intervention. Based on strong preliminary data showing
abnormalities in rate and temporal coding in cognitive impairment following ELS, we propose that aberrant
neural circuit dynamics are the neurophysiological underpinnings of cognitive impairment. In this proposal, we
wish to rigorously study the consequences of ELS on temporal coding using multi-site single cell and local field
potentials. To move from correlative to causal experimentation, we will first determine if cognitive rehabilitation
following ELS reverses coding abnormalities. Secondly, we will use optogenetic-induced modulation of
neuronal circuits to modify coding abnormalities and correct spatial cognitive deficits. Based on compelling
preliminary data, we believe our findings will support the concept of dynamic neural discoordination as a causal
factor of cognitive dysfunction following ELS.

## Key facts

- **NIH application ID:** 9889192
- **Project number:** 5R01NS108765-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Gregory L. Holmes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,680
- **Award type:** 5
- **Project period:** 2018-06-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889192

## Citation

> US National Institutes of Health, RePORTER application 9889192, Mechanisms of Cognitive Impairment Following Early-Life Seizures (5R01NS108765-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9889192. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*