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 anesthetized 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 have translational therapeutic applications.

Objective. Neural interfaces and other implantable micro-devices that use polymerencapsulated integrated circuits will only be allowed in medical devices when their lifetimes can be estimated from experimental data. An apparatus has been developed and tested that allows hundreds of insulated samples (interdigitated combs) to be aged under accelerated conditions of high temperature and voltage stress. Occasionally, aging is paused while the sample's impedance is measured; the impedance spectrogram may show degradation as it progresses before failure. Approach. The design was based on practical considerations which are reviewed. A Solartron Modulab provides the frequency response analyser and the femtoammeter. The apparatus can accommodate batches of samples at several temperatures and with different aging voltage waveforms. It is important to understand features of the spectra that are not due to comb-comb leakage, but come from other places (for example substrate-solution leakage); some have been observed and investigated using SPICE. Main results. The design is described in detail and test results show that it is capable of making measurements over long periods, at least up to 67 °C. Despite the size of the apparatus, background capacitance is about 1 pF and comb-comb capacitances of about 30 pF can be measured down to 10 mHz, an impedance of about 100 GΩ. An important discovery was the advantage of grounding the bathing solution, primarily in that it raises the measurement ceiling. Observation and SPICE simulation shows that leakage from the substrate to the bathing solution can give phase lags >90°, in contrast to comb-comb leakage which reduces phase lag to <90°. Significance. The value of this paper is that it will facilitate research into the endurance of small implanted devices because, given a description of a proven apparatus, researchers can start building their own apparatus relatively quickly and with confidence.

Objective. Ensuring the longevity of implantable devices is critical for their clinical usefulness. This is commonly achieved by hermetically sealing the sensitive electronics in a water impermeable housing, however, this method limits miniaturisation. Alternatively, silicone encapsulation has demonstrated long-term protection of implanted thick-film electronic devices. However, much of the current conformal packaging research is focused on more rigid coatings, such as parylene, liquid crystal polymers and novel inorganic layers. Here, we consider the potential of silicone to protect implants using thin-film technology with features 33 times smaller than thick-film counterparts. Approach. Aluminium interdigitated comb structures under plasma-enhanced chemical vapour deposited passivation (SiO x , SiO x N y , SiO x N y + SiC) were encapsulated in medical grade silicones, with a total of six passivation/silicone combinations. Samples were aged in phosphate-buffered saline at 67 ∘ C for up to 694 days under a continuous ±5 V biphasic waveform. Periodic electrochemical impedance spectroscopy measurements monitored for leakage currents and degradation of the metal traces. Fourier-transform infrared spectroscopy, x-ray photoelectron spectroscopy, focused-ion-beam and scanning-electron- microscopy were employed to determine any encapsulation material changes. Main results. No silicone delamination, passivation dissolution, or metal corrosion was observed during ageing. Impedances greater than 100 GΩ were maintained between the aluminium tracks for silicone encapsulation over SiO x N y and SiC passivations. For these samples the only observed failure mode was open-circuit wire bonds. In contrast, progressive hydration of the SiO x caused its resistance to decrease by an order of magnitude. Significance. These results demonstrate silicone encapsulation offers excellent protection to thin-film conducting tracks when combined with appropriate inorganic thin films. This conclusion corresponds to previous reliability studies of silicone encapsulation in aqueous environments, but with a larger sample size. Therefore, we believe silicone encapsulation to be a realistic means of providing long-term protection for the circuits of implanted electronic medical devices.