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

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.

A micropower tilt-processing circuit.

This paper describes a novel analog circuit for extracting the tilt angle from the output of a linear microelectromechanical-system accelerometer. The circuit uses the accelerometer signal, together with the gravitational acceleration vector, to generate the tilt signal. Using a current-mode representation with metal-oxide semiconductor devices operating in weak inversion, the appropriate trigonometric function has been realized to compute tilt. Furthermore, implementing a long-time constant filter to extract the mean tilt level provides adaptation to the static tilt level. Specifically, this circuit has been designed as part of an implantable vestibular prosthesis to provide inclination signals for bypassing dysfunctional otolith end organs. The circuit has been fabricated in AustriaMicroSystems 0.35-mum 2P4M complementary metal-oxide semiconductor technology, and this paper presents the theory, implementation, and measured results.

A partial-current-steering biphasic stimulation driver for vestibular prostheses.

This paper describes a novel partial-current-steering stimulation circuit for implantable vestibular prostheses. The drive hardware momentarily delivers a charge-balanced asymmetric stimulus to a dummy load before steering towards the stimulation electrodes. In this fashion, power is conserved while still gaining from the benefits of current steering. The circuit has been designed to be digitally programmable as part of an implantable vestibular prosthesis. The hardware has been implemented in AMS 0.35 mum 2P4M CMOS technology.