# Identifying brain networks to predict treatment resistance and post-surgical outcome: An ENIGMA-Epilepsy initiative

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $586,072

## Abstract

ABSTRACT
 Epilepsy is a devastating neurological illness that affects over 50 million people worldwide.
Approximately one-third of patients do not respond to anti-seizure medication (ASM) and require additional
diagnostic work-up, including consideration for surgery. Structural neuroimaging plays a pivotal role in the
diagnostic evaluation of epilepsy, identifying visible lesions in many patients that co-localize with the seizure
focus. However, up to 40% of patients have normal-appearing MRIs and this number is growing. As a result,
there is increased interest in identifying subtle brain network abnormalities that could help to delineate the
epileptogenic network and aid in the prediction of treatment response (i.e., response to ASMs and surgical
outcomes). Unfortunately, methods for reliably identifying which patients will be drug-responsive versus drug-
resistant, and which patients will achieve successful versus unsuccessful surgical outcomes are lacking.
 A major barrier to progress in this field has been obtaining quantitative imaging, including structural MRI
(sMRI) and diffusion-weighted imaging (dMRI), clinical, and genetic data on large, geographically diverse
samples of patients in whom different treatment outcomes can be evaluated. In the past, sample sizes have
been insufficient to detect subtle, but reliable, brain abnormalities in patients with focal or generalized
epilepsies that are genuinely associated with epilepsy and not with vicissitudes related to small or
geographically restricted samples.
 A new, large-scale data initiative, ENIGMA4-Epilepsy, coupled with technological advancements that
enable improved data harmonization are now lifting these barriers and allowing us to combine multi-site
sMRI/dMRI, clinical, genetic data to predict important clinical outcomes, and making the results generalizable
to a global epilepsy community. In this grant, we will leverage data collected through ENIGMA-Epilepsy—a
consortium of 24 epilepsy centers from 14 countries (more than 2,250 patient and 1,727 healthy control
sMRI/dMRI datasets) and the Human Epilepsy Project (HEP). We will include new network models (i.e.,
individualized connectomes) and polygenic risk scores (PRS) to test whether a combination of imaging,
clinical, and genetic risk can accurately predict two clinical outcomes: drug-resistance and post-operative
seizure outcome. Our scientific premise is that MRI-based assessment of whole-brain network properties, in
combination with clinical data and PRS derived from genetic data, are able to predict (i) drug response in
recently diagnosed epilepsy cases and (ii) postsurgical outcomes in individuals with drug-resistant epilepsy.
 This R01 addresses NIH's call for more reproducible studies by introducing a highly-powered design
capable of capturing variability across patients with diverse clinical characteristics and treatment outcomes.
This grant is also directly aligned with NINDS's 2020 Epilepsy Benchmarks (IIIB), which encou...

## Key facts

- **NIH application ID:** 10849658
- **Project number:** 5R01NS122827-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** CARRIE R MCDONALD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $586,072
- **Award type:** 5
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849658

## Citation

> US National Institutes of Health, RePORTER application 10849658, Identifying brain networks to predict treatment resistance and post-surgical outcome: An ENIGMA-Epilepsy initiative (5R01NS122827-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10849658. Licensed CC0.

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