# Establishing novel properties of dynamic systems models to identify epileptogenic networks in patients with drug resistant epilepsy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $446,959

## Abstract

PROJECT SUMMARY
Over 15 million epilepsy patients worldwide have medically refractory epilepsy (MRE), i.e., they do not respond
to drugs [1]. Successful surgery is a hopeful alternative for seizure freedom but can only be achieved through
complete resection or disconnection of the epileptogenic zone (EZ), the brain region(s) where seizures originate.
Unfortunately, surgical success rates vary between 30%-70% because no clinically validated biological markers
of the EZ exist. Localizing the EZ has thus become a costly and time-consuming process during which a team
of clinicians obtain imaging data (e.g. MRI, PET) and scalp EEG recordings, which is often followed by invasive
monitoring involving days-to-weeks of EEG recordings captured intracranially (iEEG). Clinicians visually inspect
iEEG data, looking for abnormal activity (e.g. low-voltage high frequency activity) on individual channels
occurring immediately before seizures. They also look for abnormal iEEG spikes that last a few seconds
occurring in between seizures. In the end, clinicians use <1% of the iEEG data captured to assist in EZ
localization (minutes of seizure data versus days of recordings), which begs the question-“are we missing
significant opportunities to leverage these largely ignored data sets to better diagnose and treat patients?”
Intracranial EEG offers a unique opportunity to observe rich epileptic cortical network dynamics, which are only
visible by the naked eye during seizures. But, waiting for seizures to occur is risky for the patient as invasive
monitoring is associated with complications including bleedings, infections, and neurological deficits. Further,
the costs of monitoring are very high, with one estimate quoting that the cost is at least $5,000 per day. In the
proposed study, we aim to leverage iEEG data in between seizures by (ii) testing a new networked-based inter-
ictal (between seizure) iEEG marker of the EZ, and by (i) modulating seizure networks with single-pulse electrical
stimulation (SPES) and analyzing the associated cortico-cortical evoked potentials (CCEPs). We hypothesize
that patient-specific dynamical network models (DNMs), built from each patient’s inter-ictal iEEG and CCEPs
data, can characterize brain network dynamics and reveal pathological nodes, i.e., the EZ. The DNM
characterizes how each iEEG node (channel) dynamically influences the rest of the network and how the network
responds to exogenous stimuli. Our team has expertise in dynamical systems modeling, signal processing of
iEEG data, electrophysiology, and surgical treatment of epilepsy, and is uniquely positioned to test our main
hypothesis through the following aims: (i) to investigate source-sink properties of DNMs derived from interictal
iEEG data to localize the EZ, (ii) to investigate resonance properties of DNMs derived from SPES evoked
responses to localize the EZ, and (iii) to test whether stimulating suspected EZ nodes with resonant periodic
pulse inputs triggers seizure...

## Key facts

- **NIH application ID:** 10445867
- **Project number:** 1R01NS122927-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jorge Alvaro Gonzalez-Martinez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $446,959
- **Award type:** 1
- **Project period:** 2022-02-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445867

## Citation

> US National Institutes of Health, RePORTER application 10445867, Establishing novel properties of dynamic systems models to identify epileptogenic networks in patients with drug resistant epilepsy (1R01NS122927-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445867. Licensed CC0.

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