Characterizing the role of the structural connectome in seizure dynamics

How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal ep...

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Published in:	Brain (London, England : 1878) Vol. 142; no. 7; p. 1955
Main Authors:	Shah, Preya, Ashourvan, Arian, Mikhail, Fadi, Pines, Adam, Kini, Lohith, Oechsel, Kelly, Das, Sandhitsu R, Stein, Joel M, Shinohara, Russell T, Bassett, Danielle S, Litt, Brian, Davis, Kathryn A
Format:	Journal Article
Language:	English
Published:	England 01.07.2019
Subjects:	Adult Brain - physiopathology Connectome Diffusion Magnetic Resonance Imaging Drug Resistance Electrocorticography Epilepsies, Partial - physiopathology Female Humans Male Middle Aged Neural Pathways - physiopathology Neuroimaging Seizures - physiopathology White Matter - physiopathology Young Adult epilepsy structural connectivity functional connectivity high-angular resolution diffusion imaging intracranial EEG
ISSN:	1460-2156, 1460-2156
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Abstract	How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural-through surgery or laser ablation-but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered intracranial EEG. Across all frequency bands, we find significant increases in structure-function coupling from pre-ictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are highly stereotyped for each patient. These results suggest that seizures harness the underlying structural connectome as they propagate. Mapping the relationship between structural and functional connectivity in epilepsy may inform new therapies to halt seizure spread, and pave the way for targeted patient-specific interventions.
AbstractList	How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural-through surgery or laser ablation-but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered intracranial EEG. Across all frequency bands, we find significant increases in structure-function coupling from pre-ictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are highly stereotyped for each patient. These results suggest that seizures harness the underlying structural connectome as they propagate. Mapping the relationship between structural and functional connectivity in epilepsy may inform new therapies to halt seizure spread, and pave the way for targeted patient-specific interventions. How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural-through surgery or laser ablation-but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered intracranial EEG. Across all frequency bands, we find significant increases in structure-function coupling from pre-ictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are highly stereotyped for each patient. These results suggest that seizures harness the underlying structural connectome as they propagate. Mapping the relationship between structural and functional connectivity in epilepsy may inform new therapies to halt seizure spread, and pave the way for targeted patient-specific interventions.How does the human brain's structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural-through surgery or laser ablation-but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered intracranial EEG. Across all frequency bands, we find significant increases in structure-function coupling from pre-ictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are highly stereotyped for each patient. These results suggest that seizures harness the underlying structural connectome as they propagate. Mapping the relationship between structural and functional connectivity in epilepsy may inform new therapies to halt seizure spread, and pave the way for targeted patient-specific interventions.
Author	Shinohara, Russell T Bassett, Danielle S Kini, Lohith Oechsel, Kelly Shah, Preya Litt, Brian Ashourvan, Arian Mikhail, Fadi Davis, Kathryn A Das, Sandhitsu R Pines, Adam Stein, Joel M
Author_xml	– sequence: 1 givenname: Preya surname: Shah fullname: Shah, Preya organization: Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA – sequence: 2 givenname: Arian surname: Ashourvan fullname: Ashourvan, Arian organization: Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA – sequence: 3 givenname: Fadi surname: Mikhail fullname: Mikhail, Fadi organization: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 4 givenname: Adam surname: Pines fullname: Pines, Adam organization: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 5 givenname: Lohith surname: Kini fullname: Kini, Lohith organization: Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA – sequence: 6 givenname: Kelly surname: Oechsel fullname: Oechsel, Kelly organization: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 7 givenname: Sandhitsu R surname: Das fullname: Das, Sandhitsu R organization: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 8 givenname: Joel M surname: Stein fullname: Stein, Joel M organization: Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 9 givenname: Russell T surname: Shinohara fullname: Shinohara, Russell T organization: Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 10 givenname: Danielle S surname: Bassett fullname: Bassett, Danielle S organization: Department of Physics and Astronomy, College of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA – sequence: 11 givenname: Brian surname: Litt fullname: Litt, Brian organization: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA – sequence: 12 givenname: Kathryn A surname: Davis fullname: Davis, Kathryn A organization: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Copyright	The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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SubjectTerms	Adult Brain - physiopathology Connectome Diffusion Magnetic Resonance Imaging Drug Resistance Electrocorticography Epilepsies, Partial - physiopathology Female Humans Male Middle Aged Neural Pathways - physiopathology Neuroimaging Seizures - physiopathology White Matter - physiopathology Young Adult
Title	Characterizing the role of the structural connectome in seizure dynamics
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