# Noninvasive Mapping of Functional and Effective Connectivity in Children with Drug Resistant Epilepsy

> **NIH NIH R01** · COOK CHILDREN'S MEDICAL CENTER · 2024 · $454,820

## Abstract

Project Summary
For children with drug-resistant epilepsy (DRE), resective surgery is the most effective treatment to achieve
seizure-freedom. Its success depends on the resection of the epileptogenic zone (EZ). The gold standard to
estimate the EZ is by recording seizures with intracranial EEG (iEEG) and localize their onset, namely the seizure
onset zone (SOZ). Yet, the SOZ does not always predict outcome, and its delineation often requires several
days of recordings to capture seizures. Moreover, iEEG presents limitations due to its invasiveness and often
leads to erroneous results. Noninvasive electrophysiological techniques, which can record interictal spikes from
the whole brain, could overcome the iEEG limitations. However, spikes suffer from low specificity to the EZ
mostly because they propagate across large brain areas forming epileptic networks. These networks are often
larger than the EZ and thus may overlap with eloquent areas that should be preserved. Understanding of the
functional architecture of the epileptic networks may allow for selective disruption (or modulation) of key
components of these networks to halt seizures without removing the entire network. This approach could
potentially improve the post-operative seizure control and help prevent post-operative functional deficits. This
application aims to construct normative functional and effective connectivity brain maps from typically developing
children, assess whether functional and effective connectivity deviations from normative predict the EZ and
surgical outcome in children with DRE, and reveal the relationship between propagating interictal activity and
information flow among spikes onset and areas of spread. We hypothesize that: (1) hubs with deviated functional
and effective connectivity (i.e., high functional connectivity and outwards information flow) from normative identify
the EZ in children with DRE; (2) resection of pathological hubs disrupts the epileptogenic network predicting
outcome better than the SOZ; (3) information flows outwards from spike onset to areas of spread; and (4) hubs
with deviated (from normative) functional and effective connectivity values overlap with the onset of spike
propagation. To test our hypotheses, we will pursue the following specific aims: (1) construct normative maps
from noninvasive data and compare with data from children with DRE; (2) assess whether functional and effective
connectivity deviations from normative maps predict the EZ and surgical outcome; and (3) reveal the relationship
between information flow and epileptiform propagating activity. To pursue these aims, we will record HD-EEG
and MEG data from 70 children (4-18 years old) with MRE and 70 age- and gender-matched typically developing
children. This application combines the use of cutting-edge pediatric neuroimaging instruments and innovative
signal processing tools together with extensive neuroimaging experience with children. Our research will have a
direct imp...

## Key facts

- **NIH application ID:** 10779862
- **Project number:** 1R01NS134944-01
- **Recipient organization:** COOK CHILDREN'S MEDICAL CENTER
- **Principal Investigator:** Christos Papadelis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,820
- **Award type:** 1
- **Project period:** 2024-02-09 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779862

## Citation

> US National Institutes of Health, RePORTER application 10779862, Noninvasive Mapping of Functional and Effective Connectivity in Children with Drug Resistant Epilepsy (1R01NS134944-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10779862. Licensed CC0.

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