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 journalArticlepeer-review


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 languageEnglish
Pages (from-to)559–575
Number of pages17
JournalNature Biomedical Engineering
Issue number4
Early online date20 Oct 2022
Publication statusPublished - 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 ( ). A.J. is a Wellcome Trust Senior Research Fellow (grant no. 106149; to A.J.).


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


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