Neural fragility as an EEG marker of the seizure onset zone

Adam Li; Chester Huynh; Zachary Fitzgerald; Iahn Cajigas; Damian Brusko; Jonathan Jagid; Angel O. Claudio; Andres M. Kanner; Jennifer Hopp; Stephanie Chen; Jennifer Haagensen; Emily Johnson; William Anderson; Nathan Crone; Sara Inati; Kareem A. Zaghloul; Juan Bulacio; Jorge Gonzalez-Martinez; Sridevi V. Sarma

doi:10.1038/s41593-021-00901-w

Neural fragility as an EEG marker of the seizure onset zone

Adam Li, Chester Huynh, Zachary Fitzgerald, Iahn Cajigas, Damian Brusko, Jonathan Jagid, Angel O. Claudio, Andres M. Kanner, Jennifer Hopp, Stephanie Chen, Jennifer Haagensen, Emily Johnson, William Anderson, Nathan Crone, Sara Inati, Kareem A. Zaghloul, Juan Bulacio, Jorge Gonzalez-Martinez, Sridevi V. Sarma

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Over 15 million patients with epilepsy worldwide do not respond to drugs. Successful surgical treatment requires complete removal or disconnection of the seizure onset zone (SOZ), brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30 and 70% because no clinically validated biological marker of the SOZ exists. We develop and retrospectively validate a new electroencephalogram (EEG) marker—neural fragility—in a retrospective analysis of 91 patients by using neural fragility of the annotated SOZ as a metric to predict surgical outcomes. Fragility predicts 43 out of 47 surgical failures, with an overall prediction accuracy of 76% compared with the accuracy of clinicians at 48% (successful outcomes). In failed outcomes, we identify fragile regions that were untreated. When compared to 20 EEG features proposed as SOZ markers, fragility outperformed in predictive power and interpretability, which suggests neural fragility as an EEG biomarker of the SOZ.

Original language	English (US)
Pages (from-to)	1465-1474
Number of pages	10
Journal	Nature neuroscience
Volume	24
Issue number	10
DOIs	https://doi.org/10.1038/s41593-021-00901-w
State	Published - Oct 2021

ASJC Scopus subject areas

General Neuroscience

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10.1038/s41593-021-00901-w

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Li, A., Huynh, C., Fitzgerald, Z., Cajigas, I., Brusko, D., Jagid, J., Claudio, A. O., Kanner, A. M., Hopp, J., Chen, S., Haagensen, J., Johnson, E., Anderson, W., Crone, N., Inati, S., Zaghloul, K. A., Bulacio, J., Gonzalez-Martinez, J., & Sarma, S. V. (2021). Neural fragility as an EEG marker of the seizure onset zone. Nature neuroscience, 24(10), 1465-1474. https://doi.org/10.1038/s41593-021-00901-w

Li, A, Huynh, C, Fitzgerald, Z, Cajigas, I, Brusko, D, Jagid, J, Claudio, AO, Kanner, AM, Hopp, J, Chen, S, Haagensen, J, Johnson, E , Anderson, W , Crone, N, Inati, S, Zaghloul, KA, Bulacio, J, Gonzalez-Martinez, J & Sarma, SV 2021, 'Neural fragility as an EEG marker of the seizure onset zone', Nature neuroscience, vol. 24, no. 10, pp. 1465-1474. https://doi.org/10.1038/s41593-021-00901-w

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title = "Neural fragility as an EEG marker of the seizure onset zone",

abstract = "Over 15 million patients with epilepsy worldwide do not respond to drugs. Successful surgical treatment requires complete removal or disconnection of the seizure onset zone (SOZ), brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30 and 70% because no clinically validated biological marker of the SOZ exists. We develop and retrospectively validate a new electroencephalogram (EEG) marker—neural fragility—in a retrospective analysis of 91 patients by using neural fragility of the annotated SOZ as a metric to predict surgical outcomes. Fragility predicts 43 out of 47 surgical failures, with an overall prediction accuracy of 76% compared with the accuracy of clinicians at 48% (successful outcomes). In failed outcomes, we identify fragile regions that were untreated. When compared to 20 EEG features proposed as SOZ markers, fragility outperformed in predictive power and interpretability, which suggests neural fragility as an EEG biomarker of the SOZ.",

author = "Adam Li and Chester Huynh and Zachary Fitzgerald and Iahn Cajigas and Damian Brusko and Jonathan Jagid and Claudio, {Angel O.} and Kanner, {Andres M.} and Jennifer Hopp and Stephanie Chen and Jennifer Haagensen and Emily Johnson and William Anderson and Nathan Crone and Sara Inati and Zaghloul, {Kareem A.} and Juan Bulacio and Jorge Gonzalez-Martinez and Sarma, {Sridevi V.}",

note = "Funding Information: A.L. is supported by NIH T32 EB003383, the NSF GRFP (DGE-1746891), the Arcs Chapter Scholarship, the Whitaker Fellowship and the Chateaubriand Fellowship. S.V.S. is supported by NIH R21 NS103113, the Coulter Foundation, the Maryland Innovation Initiative, a US NSF Career Award 1055560 and the Burroughs Wellcome Fund CASI Award 1007274. E.J. is supported by NIA K23 AG063899. I.C. was partially supported by NIH R25NS108937-02. K.A.Z. and S.I. are supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. S.C. is supported by 1UL1TR003098-01 and the UMB Institute for Clinical and Translational Research. J. Hopp is supported by NINDS 1 UO1 NS08803401—Established Status Epilepticus Treatment Trial (ESETT), MII TA Grant 20180828 TEDCO—EpiWatch: A Mobile Health Application for Epilepsy Management and U10 NS058932-01 NIH NINDS—{\textquoteleft}Neurological Emergencies Treatment Trials (NETT) Network Clinical/Site Hub{\textquoteright}. Computational resources were also provided by the Maryland Advanced Research Computing Center (MARCC). The authors would like to thank C. Priebe for useful discussions on statistical analyses, J. Vogelstein for introducing A.L. to the concepts of structured RFs, S. Kim and R. J. Smith for very helpful reviews of the manuscript and M. Breault for help in creating brain figures. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2021",

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doi = "10.1038/s41593-021-00901-w",

language = "English (US)",

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AU - Li, Adam

AU - Huynh, Chester

AU - Fitzgerald, Zachary

AU - Cajigas, Iahn

AU - Brusko, Damian

AU - Jagid, Jonathan

AU - Claudio, Angel O.

AU - Kanner, Andres M.

AU - Hopp, Jennifer

AU - Chen, Stephanie

AU - Haagensen, Jennifer

AU - Johnson, Emily

AU - Anderson, William

AU - Crone, Nathan

AU - Inati, Sara

AU - Zaghloul, Kareem A.

AU - Bulacio, Juan

AU - Gonzalez-Martinez, Jorge

AU - Sarma, Sridevi V.

N1 - Funding Information: A.L. is supported by NIH T32 EB003383, the NSF GRFP (DGE-1746891), the Arcs Chapter Scholarship, the Whitaker Fellowship and the Chateaubriand Fellowship. S.V.S. is supported by NIH R21 NS103113, the Coulter Foundation, the Maryland Innovation Initiative, a US NSF Career Award 1055560 and the Burroughs Wellcome Fund CASI Award 1007274. E.J. is supported by NIA K23 AG063899. I.C. was partially supported by NIH R25NS108937-02. K.A.Z. and S.I. are supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. S.C. is supported by 1UL1TR003098-01 and the UMB Institute for Clinical and Translational Research. J. Hopp is supported by NINDS 1 UO1 NS08803401—Established Status Epilepticus Treatment Trial (ESETT), MII TA Grant 20180828 TEDCO—EpiWatch: A Mobile Health Application for Epilepsy Management and U10 NS058932-01 NIH NINDS—‘Neurological Emergencies Treatment Trials (NETT) Network Clinical/Site Hub’. Computational resources were also provided by the Maryland Advanced Research Computing Center (MARCC). The authors would like to thank C. Priebe for useful discussions on statistical analyses, J. Vogelstein for introducing A.L. to the concepts of structured RFs, S. Kim and R. J. Smith for very helpful reviews of the manuscript and M. Breault for help in creating brain figures. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

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Neural fragility as an EEG marker of the seizure onset zone

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