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Research Article

Time-evolving controllability of effective connectivity networks during seizure progression

View ORCID ProfileBrittany H. Scheid, View ORCID ProfileArian Ashourvan, View ORCID ProfileJennifer Stiso, Kathryn A. Davis, View ORCID ProfileFadi Mikhail, View ORCID ProfileFabio Pasqualetti, View ORCID ProfileBrian Litt, and View ORCID ProfileDanielle S. Bassett
  1. aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
  2. bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
  3. cDepartment of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104;
  4. dDepartment of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104;
  5. eDepartment of Mechanical Engineering, University of California, Riverside, CA 92521;
  6. fDepartment of Electrical & Systems Engineering, University of Pennsylvania, Philadelphia, PA 19104;
  7. gDepartment of Physics & Astronomy, University of Pennsylvania, Philadelphia, PA 19104;
  8. hDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
  9. iSanta Fe Institute, Santa Fe, NM 87501

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PNAS February 2, 2021 118 (5) e2006436118; https://doi.org/10.1073/pnas.2006436118
Brittany H. Scheid
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
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  • ORCID record for Brittany H. Scheid
Arian Ashourvan
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
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  • ORCID record for Arian Ashourvan
Jennifer Stiso
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
cDepartment of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104;
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Kathryn A. Davis
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
dDepartment of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104;
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Fadi Mikhail
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
dDepartment of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104;
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Fabio Pasqualetti
eDepartment of Mechanical Engineering, University of California, Riverside, CA 92521;
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  • ORCID record for Fabio Pasqualetti
Brian Litt
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
dDepartment of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104;
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  • ORCID record for Brian Litt
Danielle S. Bassett
aDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
bCenter for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
fDepartment of Electrical & Systems Engineering, University of Pennsylvania, Philadelphia, PA 19104;
gDepartment of Physics & Astronomy, University of Pennsylvania, Philadelphia, PA 19104;
hDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
iSanta Fe Institute, Santa Fe, NM 87501
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  • ORCID record for Danielle S. Bassett
  • For correspondence: dsb@seas.upenn.edu
  1. Edited by György Buzsáki, New York University Langone Medical Center, New York, NY, and approved December 24, 2020 (received for review April 7, 2020)

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Significance

Responsive neurostimulation is an increasingly accessible treatment for medication-resistant epilepsy that aims to suppress seizures using electrical stimulation from implanted intracranial electrodes. However, the optimal cortical location and time point for intervening once a seizure begins are not well understood. Here we represent a seizure as a series of effective connectivity networks over time and compute metrics of network controllability and optimal control energy. Our results allow us to characterize when and where the brain network may be the most responsive to an external stimulus.

Abstract

Over one third of the estimated 3 million people with epilepsy in the United States are medication resistant. Responsive neurostimulation from chronically implanted electrodes provides a promising treatment alternative to resective surgery. However, determining optimal personalized stimulation parameters, including when and where to intervene to guarantee a positive patient outcome, is a major open challenge. Network neuroscience and control theory offer useful tools that may guide improvements in parameter selection for control of anomalous neural activity. Here we use a method to characterize dynamic controllability across consecutive effective connectivity (EC) networks based on regularized partial correlations between implanted electrodes during the onset, propagation, and termination regimes of 34 seizures. We estimate regularized partial correlation adjacency matrices from 1-s time windows of intracranial electrocorticography recordings using the Graphical Least Absolute Shrinkage and Selection Operator (GLASSO). Average and modal controllability metrics calculated from each resulting EC network track the time-varying controllability of the brain on an evolving landscape of conditionally dependent network interactions. We show that average controllability increases throughout a seizure and is negatively correlated with modal controllability throughout. Our results support the hypothesis that the energy required to drive the brain to a seizure-free state from an ictal state is smallest during seizure onset, yet we find that applying control energy at electrodes in the seizure onset zone may not always be energetically favorable. Our work suggests that a low-complexity model of time-evolving controllability may offer insights for developing and improving control strategies targeting seizure suppression.

  • effective connectivity
  • network topology
  • controllability
  • epilepsy
  • GLASSO

Footnotes

  • ↵1To whom correspondence should be addressed. Email: dsb{at}seas.upenn.edu.
  • Author contributions: B.H.S. and D.S.B. designed research; B.H.S. performed research; B.H.S., A.A., K.A.D., F.M., B.L., and D.S.B. analyzed data; and B.H.S., A.A., J.S., F.P., B.L., and D.S.B. wrote the paper.

  • The authors declare no competing interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2006436118/-/DCSupplemental.

Data Availability.

Anonymized iEEG were retrieved from the publicly accessible database hosted on the International Epilepsy Electrophysiology Portal (www.ieeg.org) (50).

  • Copyright © 2021 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

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Time-evolving controllability of effective connectivity networks during seizure progression
Brittany H. Scheid, Arian Ashourvan, Jennifer Stiso, Kathryn A. Davis, Fadi Mikhail, Fabio Pasqualetti, Brian Litt, Danielle S. Bassett
Proceedings of the National Academy of Sciences Feb 2021, 118 (5) e2006436118; DOI: 10.1073/pnas.2006436118

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Time-evolving controllability of effective connectivity networks during seizure progression
Brittany H. Scheid, Arian Ashourvan, Jennifer Stiso, Kathryn A. Davis, Fadi Mikhail, Fabio Pasqualetti, Brian Litt, Danielle S. Bassett
Proceedings of the National Academy of Sciences Feb 2021, 118 (5) e2006436118; DOI: 10.1073/pnas.2006436118
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  • Biological Sciences
  • Neuroscience
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Proceedings of the National Academy of Sciences: 118 (5)
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