# Stress-Induced Hormonal Fluctuations and their Relation to Seizure Dynamics in Children with Epilepsy

> **NIH NIH R03** · BOSTON CHILDREN'S HOSPITAL · 2020 · $177,000

## Abstract

PROJECT SUMMARY/ABSTRACT
In the new era of personalized medicine, the epilepsy field is at a tipping point to leverage emerging
therapies that can being tailored to individual patient characteristics. Over 30% of children with
epilepsy suffer from seizures that cannot be managed by mono- or poly-pharmacotherapies. Targeted
neurostimulation and drug delivery are promising alternative therapies but, given the complexity and
heterogeneity of the disorder, these therapies need to be precisely guided by the patient’s seizure
dynamics. Despite decades of basic and clinical research, the latter remain elusive. In particular,
seizure evolution from ictogenesis to ictal onset is poorly understood, in part due to a lack of
fundamental understanding of how seizure precipitants impact the brain’s neurophysiological
equilibrium, trigger ictogenesis and lead to cumulative changes that facilitate ictal onset. Although the
underlying mechanisms of action of common precipitants such as stress and sleep loss are unclear,
there is substantial evidence that they may modulate various hormones and neurotransmitters that
impact the brain’s excitability and/or balance between excitation and inhibition. This project aims to
systematically investigate the impact of large-scale hormonal fluctuations in pediatric epilepsy patients
on brain dynamics, and quantify localized and distributed (network-level) electrophysiological changes
during seizure evolution. Specifically, in a cohort of n = 40 patients with focal epilepsy who are
undergoing continuous noninvasive neurophysiological monitoring as part of their presurgical
evaluation, salivary cortisol and catecholamines will be measured 8 times daily, across all study days
(Aim 1). Continuous scalp electroncephalograms (EEG) collected during this period will be analyzed in
their entirety at the signal and network levels (Aim 2). Pathological high-frequency oscillations, a
promising precursor of seizure activity in the epileptic brain will be estimated and classified across the
entire period of recording. Multiscale brain networks and their topological properties will be quantified
across all dominant frequencies of continuous EEG signals, and their time-dependent seizure
sensitivity and specificity will be assessed. Statistical models will be developed to evaluate the relation
between each patient-specific circadian hormone rhythms and corresponding temporal patterns of
estimated electrophysiological measures, individually and combined into a seizure risk score (Aim 3).
This is a first of its kind study that may significantly improve the field’s understanding of the direct and
indirect (through hormonal modulations) impact of seizure precipitants, such as stress, on seizure
dynamics from ictogenesis to ictal onset. This new knowledge may have a significant impact on the
development of next-generation therapies that need to be guided by patient-specific seizure dynamics.

## Key facts

- **NIH application ID:** 10105451
- **Project number:** 1R03NS119799-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Catherine Stamoulis
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105451

## Citation

> US National Institutes of Health, RePORTER application 10105451, Stress-Induced Hormonal Fluctuations and their Relation to Seizure Dynamics in Children with Epilepsy (1R03NS119799-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10105451. Licensed CC0.

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