Towards network-guided neuromodulation for epilepsy

Rory J. Piper; R. Mark Richardson; Gregory Worrell; David W. Carmichael; Torsten Baldeweg; Brian Litt; Timothy Denison; Martin M. Tisdall

doi:10.1093/brain/awac234

Towards network-guided neuromodulation for epilepsy

Rory J. Piper^*, R. Mark Richardson, Gregory Worrell, David W. Carmichael, Torsten Baldeweg, Brian Litt, Timothy Denison, Martin M. Tisdall

^*Corresponding author for this work

Biomedical Engineering Department

Research output: Contribution to journal › Review article › peer-review

32 Citations (Scopus)

Abstract

Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.

Original language	English
Pages (from-to)	3347-3362
Number of pages	16
Journal	Brain
Volume	145
Issue number	10
DOIs	https://doi.org/10.1093/brain/awac234
Publication status	Published - 1 Oct 2022

Keywords

connectivity
deep brain stimulation
epilepsy
networks
responsive neurostimulation

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10.1093/brain/awac234

Cite this

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title = "Towards network-guided neuromodulation for epilepsy",

abstract = "Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.",

keywords = "connectivity, deep brain stimulation, epilepsy, networks, responsive neurostimulation",

author = "Piper, {Rory J.} and Richardson, {R. Mark} and Gregory Worrell and Carmichael, {David W.} and Torsten Baldeweg and Brian Litt and Timothy Denison and Tisdall, {Martin M.}",

note = "Funding Information: This work is supported by the NIHR GOSH BRC. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. R.J.P. is funded by the Great Ormond Street Hospital Children's Charity Lewis Spitz Surgeon-Scientist PhD programme. B.L. is funded by National Institutes of Health grants 1DP1 OD029758-01, R56 NS 099348-05A1, The Pennsylvania Health Research Formula Fund, and the Mirowski Family Foundation. D.W.C. is supported by the Wellcome Centre for Medical Engineering. R.M.R. is funded by National Institutes of Health grant R01 NS110424. G.W. is supported by National Institutes of Health (UH2/UH3 NS95495 and R01 NS09288203). Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.",

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T1 - Towards network-guided neuromodulation for epilepsy

AU - Piper, Rory J.

AU - Richardson, R. Mark

AU - Worrell, Gregory

AU - Carmichael, David W.

AU - Baldeweg, Torsten

AU - Litt, Brian

AU - Denison, Timothy

AU - Tisdall, Martin M.

N1 - Funding Information: This work is supported by the NIHR GOSH BRC. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. R.J.P. is funded by the Great Ormond Street Hospital Children's Charity Lewis Spitz Surgeon-Scientist PhD programme. B.L. is funded by National Institutes of Health grants 1DP1 OD029758-01, R56 NS 099348-05A1, The Pennsylvania Health Research Formula Fund, and the Mirowski Family Foundation. D.W.C. is supported by the Wellcome Centre for Medical Engineering. R.M.R. is funded by National Institutes of Health grant R01 NS110424. G.W. is supported by National Institutes of Health (UH2/UH3 NS95495 and R01 NS09288203). Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.

PY - 2022/10/1

Y1 - 2022/10/1

N2 - Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.

AB - Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.

KW - connectivity

KW - deep brain stimulation

KW - epilepsy

KW - networks

KW - responsive neurostimulation

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U2 - 10.1093/brain/awac234

DO - 10.1093/brain/awac234

M3 - Review article

C2 - 35771657

AN - SCOPUS:85144669699

SN - 0006-8950

VL - 145

SP - 3347

EP - 3362

JO - Brain

JF - Brain

IS - 10

ER -

Towards network-guided neuromodulation for epilepsy

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Keywords

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