# Network dynamics of sleep-wake states in epilepsy

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $216,972

## Abstract

PROJECT SUMMARY/ABSTRACT
Of 46 million people worldwide with active epilepsy, one third are drug-resistant. Emerging neuromodulation-
based therapies have demonstrated great potential to reduce seizure frequency and improve the quality of life
in patients with drug-resistant epilepsy over time. The mechanisms underlying such therapies are thought to
relate to the progressive restructuring of the epileptogenic network toward dynamics that reduce epileptic
activity. Yet, the network properties underlying low and high epileptic potential are poorly understood, and the
management of neuromodulatory therapies thus remains largely empiric with variable outcomes. To move
toward rational approaches rooted in mechanistic understanding, there is a critical need to first fundamentally
understand how network dynamics influence epileptogenic activity. In this proposal, we turn to the rich
relationship between sleep and epilepsy, as sleep-wake states offer a robust and systematic way to cycle
through a wide range of network dynamics that are strongly associated with different epileptic potentials. By
leveraging sleep-wake states as a portal to probing dynamic brain networks, the overall objective of this
proposal is to identify salient network features that represent states of variable epileptogenic potential and to
determine associated network mechanisms that indicate reconfiguration into epileptogenic states. Using a
combination of magnetoencephalography (MEG) imaging and diffusion tensor imaging (DTI)/tractography, I will
first identify physiologic network dynamics of sleep-wake states in patients with focal epilepsy (Aim 1). I will
then identify state-dependent network predictors and develop biophysical models of pathologic states
predictive of interictal epileptiform activity (Aim 2). The expected outcome of this work is to gain a deeper
understanding of key network features that augment epileptic potential and insight into their underlying
mechanisms. This proposal combines an innovative research project with translational implications and a
rigorous training and career development plan, which are highly complementary and together will facilitate my
transition into an independent physician-scientist. I have assembled a leading, multidisciplinary mentorship
team that has a constellation of expertise aligned with my research and training goals, including in epilepsy,
sleep, MEG imaging, structural-function network analysis, neural computation, and biostatistics. In addition,
through formal training, coursework, and directed mentorship, I will advance my skills in the areas of signal
processing, machine learning, dynamical models, sleep electrophysiology, and clinical trials, which I will
continue to use throughout my scientific career. The knowledge and training obtained during this award period
will enable me to establish a robust independent research program that leverages multimodal
electrophysiology and imaging in humans and insights from the rich rela...

## Key facts

- **NIH application ID:** 10763413
- **Project number:** 5K23NS125123-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Joline Fan
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,972
- **Award type:** 5
- **Project period:** 2023-01-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763413

## Citation

> US National Institutes of Health, RePORTER application 10763413, Network dynamics of sleep-wake states in epilepsy (5K23NS125123-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10763413. Licensed CC0.

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