Closed-loop optogenetic control of the dynamics of neural activity in non-human primates

Boubker Zaaimi; Douglass M. Turnbull; A. Hazra; Yucan Wang; C. Gandara; F. McLeod; E. E. McDermott; E. Escobedo-Cousin; A. Shah Idil; R. G. Bailey; S. Tardio; A. Patel; N. Ponon; J. Gausden; D. Walsh; F. Hutchings; M. Kaiser; Mark O. Cunningham; G. J. Clowry; Fiona E. N. LeBeau; T. G. Constandinou; S. N. Baker; N. Donaldson; P. Degenaar; A. O’Neill; A. J. Trevelyan; A. Jackson

doi:10.1038/s41551-022-00945-8

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates

Boubker Zaaimi, Douglass M. Turnbull, A. Hazra, Yucan Wang, C. Gandara, F. McLeod, E. E. McDermott, E. Escobedo-Cousin, A. Shah Idil, R. G. Bailey, S. Tardio, A. Patel, N. Ponon, J. Gausden, D. Walsh, F. Hutchings, M. Kaiser, Mark O. Cunningham, G. J. Clowry, Fiona E. N. LeBeauT. G. Constandinou, S. N. Baker, N. Donaldson, P. Degenaar, A. O’Neill, A. J. Trevelyan, A. Jackson^*

^*Corresponding author for this work

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

Abstract

Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

Original language	English
Pages (from-to)	559–575
Number of pages	17
Journal	Nature Biomedical Engineering
Volume	7
Issue number	4
Early online date	20 Oct 2022
DOIs	https://doi.org/10.1038/s41551-022-00945-8
Publication status	Published - Apr 2023

Bibliographical note

Funding Information:
The project CANDO (Controlling Abnormal Network Dynamics with Optogenetics) is co-funded by the Wellcome Trust (grant no. 102037; to A.J., A.O., S.N.B., G.J.C., M.O.C., P.D., M.K., F.E.N.L. and A.J.T.) and the Engineering and Physical Sciences Research Council (grant no. A000026; to A.J., A.O., S.N.B., G.J.C., M.O.C., P.D., M.K., F.E.N.L. and A.J.T.). We thank all members of the CANDO consortium ( www.cando.ac.uk ). A.J. is a Wellcome Trust Senior Research Fellow (grant no. 106149; to A.J.).

Keywords

Biomedical Engineering
Computational Neuroscience
Neurology
Closed-loop Optogenetic Control
Network Dynamics
Excitatory Opsins (CLOSe)
Electrical Neurostimulation

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Zaaimi, B., Turnbull, D. M., Hazra, A., Wang, Y., Gandara, C., McLeod, F., McDermott, E. E., Escobedo-Cousin, E., Idil, A. S., Bailey, R. G., Tardio, S., Patel, A., Ponon, N., Gausden, J., Walsh, D., Hutchings, F., Kaiser, M., Cunningham, M. O., Clowry, G. J., ... Jackson, A. (2023). Closed-loop optogenetic control of the dynamics of neural activity in non-human primates. Nature Biomedical Engineering, 7(4), 559–575. https://doi.org/10.1038/s41551-022-00945-8

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title = "Closed-loop optogenetic control of the dynamics of neural activity in non-human primates",

abstract = "Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.",

keywords = "Biomedical Engineering, Computational Neuroscience, Neurology, Closed-loop Optogenetic Control, Network Dynamics, Excitatory Opsins (CLOSe), Electrical Neurostimulation",

author = "Boubker Zaaimi and Turnbull, {Douglass M.} and A. Hazra and Yucan Wang and C. Gandara and F. McLeod and McDermott, {E. E.} and E. Escobedo-Cousin and Idil, {A. Shah} and Bailey, {R. G.} and S. Tardio and A. Patel and N. Ponon and J. Gausden and D. Walsh and F. Hutchings and M. Kaiser and Cunningham, {Mark O.} and Clowry, {G. J.} and LeBeau, {Fiona E. N.} and Constandinou, {T. G.} and Baker, {S. N.} and N. Donaldson and P. Degenaar and A. O{\textquoteright}Neill and Trevelyan, {A. J.} and A. Jackson",

note = "Funding Information: The project CANDO (Controlling Abnormal Network Dynamics with Optogenetics) is co-funded by the Wellcome Trust (grant no. 102037; to A.J., A.O., S.N.B., G.J.C., M.O.C., P.D., M.K., F.E.N.L. and A.J.T.) and the Engineering and Physical Sciences Research Council (grant no. A000026; to A.J., A.O., S.N.B., G.J.C., M.O.C., P.D., M.K., F.E.N.L. and A.J.T.). We thank all members of the CANDO consortium ( www.cando.ac.uk ). A.J. is a Wellcome Trust Senior Research Fellow (grant no. 106149; to A.J.). ",

year = "2023",

month = apr,

doi = "10.1038/s41551-022-00945-8",

language = "English",

volume = "7",

pages = "559–575",

number = "4",

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Zaaimi, B, Turnbull, DM, Hazra, A, Wang, Y, Gandara, C, McLeod, F, McDermott, EE, Escobedo-Cousin, E, Idil, AS, Bailey, RG, Tardio, S, Patel, A, Ponon, N, Gausden, J, Walsh, D, Hutchings, F, Kaiser, M, Cunningham, MO, Clowry, GJ, LeBeau, FEN, Constandinou, TG, Baker, SN, Donaldson, N, Degenaar, P, O’Neill, A, Trevelyan, AJ & Jackson, A 2023, 'Closed-loop optogenetic control of the dynamics of neural activity in non-human primates', Nature Biomedical Engineering, vol. 7, no. 4, pp. 559–575. https://doi.org/10.1038/s41551-022-00945-8

TY - JOUR

T1 - Closed-loop optogenetic control of the dynamics of neural activity in non-human primates

AU - Zaaimi, Boubker

AU - Turnbull, Douglass M.

AU - Hazra, A.

AU - Wang, Yucan

AU - Gandara, C.

AU - McLeod, F.

AU - McDermott, E. E.

AU - Escobedo-Cousin, E.

AU - Idil, A. Shah

AU - Bailey, R. G.

AU - Tardio, S.

AU - Patel, A.

AU - Ponon, N.

AU - Gausden, J.

AU - Walsh, D.

AU - Hutchings, F.

AU - Kaiser, M.

AU - Cunningham, Mark O.

AU - Clowry, G. J.

AU - LeBeau, Fiona E. N.

AU - Constandinou, T. G.

AU - Baker, S. N.

AU - Donaldson, N.

AU - Degenaar, P.

AU - O’Neill, A.

AU - Trevelyan, A. J.

AU - Jackson, A.

N1 - Funding Information: The project CANDO (Controlling Abnormal Network Dynamics with Optogenetics) is co-funded by the Wellcome Trust (grant no. 102037; to A.J., A.O., S.N.B., G.J.C., M.O.C., P.D., M.K., F.E.N.L. and A.J.T.) and the Engineering and Physical Sciences Research Council (grant no. A000026; to A.J., A.O., S.N.B., G.J.C., M.O.C., P.D., M.K., F.E.N.L. and A.J.T.). We thank all members of the CANDO consortium ( www.cando.ac.uk ). A.J. is a Wellcome Trust Senior Research Fellow (grant no. 106149; to A.J.).

PY - 2023/4

Y1 - 2023/4

N2 - Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

AB - Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

KW - Biomedical Engineering

KW - Computational Neuroscience

KW - Neurology

KW - Closed-loop Optogenetic Control

KW - Network Dynamics

KW - Excitatory Opsins (CLOSe)

KW - Electrical Neurostimulation

UR - https://www.nature.com/articles/s41551-022-00945-8

UR - https://data.ncl.ac.uk/articles/dataset/Closed-loop_optogenetic_control_of_neural_network_dynamics/19519630

U2 - 10.1038/s41551-022-00945-8

DO - 10.1038/s41551-022-00945-8

M3 - Article

C2 - 36266536

AN - SCOPUS:85140219126

VL - 7

SP - 559

EP - 575

JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 4

ER -

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates

Abstract

Bibliographical note

Keywords

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