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.
|Journal||Nature Biomedical Engineering|
|Publication status||Published - 20 Oct 2022|
Bibliographical noteFunding 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.).
- Biomedical Engineering
- Computational Neuroscience
- Closed-loop Optogenetic Control
- Network Dynamics
- Excitatory Opsins (CLOSe)
- Electrical Neurostimulation