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.

Heated humidified high-flow nasal cannula therapy in children.

Heated humidified high-flow nasal cannula therapy (HHHFNC) was originally described as a mode of respiratory support in premature neonates and is now increasingly used in the management of acute respiratory failure in older infants and children. Heating and humidification of gas mixtures allow comfortable delivery of flow rates that match or exceed the patient's inspiratory flow rate. Emerging evidence from observational studies suggests that the use of HHHFNC therapy may be associated with reduced work of breathing, improved ventilation efficiency and a decreased need for intubation in children with respiratory insufficiency. There are several proposed mechanisms of action, and the potential for provision of unpredictable positive distending pressure has caused concern. Randomised controlled trial evidence comparing clinical outcomes with those achieved using other forms of respiratory support is, however, awaited. We review the proposed mechanisms of actions, indications, advantages and complications of HHHFNC therapy in children and describe our approach to its use in the paediatric ward environment.