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.

Antagonistic contact on a dental restoration may produce surface and subsurface stresses leading to fatigue wear as well as to bulk stressing, eventually causing catastrophic failure. It was the aim of the present work to study the outcome of two different approaches to fatigue testing of materials involving either surface contact fatigue or flexural fatigue mechanisms. A range of materials was tested, including conventional glass-ionomers, resin-modified glass-ionomers, poly-acid modified composites, and composites. Materials were prepared and tested using both surface contact and flexural fatigue. The results show that conventional glass-ionomers have the least resistance to fatigue under both regimes while composites have the longest fatigue lives and the highest values of flexural fatigue limit. However, the results also support the fact that catastrophic failure should be investigated separately from surface contact fatigue. Within the group of composite products tested, a hybrid composite material had a significantly greater flexural fatigue limit than a microfilled one, but the latter material had a significantly greater surface contact fatigue life, indicating that wear behavior cannot be predicted from bulk fracture characteristics and vice versa. The process of wear occurs by a combination of a number of fundamental processes, and the contribution fatigue makes will vary according to the environment and nature of the material.