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Lookup NU author(s): Dr Boubker Zaaimi, Mark Turnbull, Dr Anupam Hazra, Professor Yujiang WangORCiD, Dr Carolina Gandara de Souza, Dr Faye McLeodORCiD, Dr Elaine Mcdermott, Dr Enrique Escobedo-Cousin, Dr Richard Bailey, Dr Sabrina Tardio, Aaliyah Patel, Dr Nilhil Ponon, Dr Johannes Gausden, Dr Darren Walsh, Frances Hutchings, Professor Marcus Kaiser, Dr Gavin ClowryORCiD, Dr Fiona LeBeauORCiD, Professor Stuart BakerORCiD, Professor Patrick Degenaar, Professor Anthony O'Neill, Professor Andrew Trevelyan, Professor Andrew Jackson
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© 2022, The Author(s), under exclusive licence to Springer Nature Limited. 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.
Author(s): Zaaimi B, Turnbull M, 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
Publication type: Article
Publication status: Published
Journal: Nature Biomedical Engineering
Year: 2023
Volume: 7
Pages: 559-575
Print publication date: 01/04/2023
Online publication date: 20/10/2022
Acceptance date: 14/08/2022
ISSN (electronic): 2157-846X
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41551-022-00945-8
DOI: 10.1038/s41551-022-00945-8
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