DyNeuMo Mk-2: An Investigational Circadian-Locked Neuromodulator with Responsive Stimulation for Applied Chronobiology.

ABSTRACT

Deep brain stimulation (DBS) for Parkinson's disease, essential tremor and epilepsy is an established palliative treatment. DBS uses electrical neuromodulation to suppress symptoms. Most current systems provide a continuous pattern of fixed stimulation, with clinical follow-ups to refine settings constrained to normal office hours. An issue with this management strategy is that the impact of stimulation on circadian, i.e. sleep-wake, rhythms is not fully considered; either in the device design or in the clinical follow-up. Since devices can be implanted in brain targets that couple into the reticular activating network, impact on wakefulness and sleep can be significant. This issue will likely grow as new targets are explored, with the potential to create entraining signals that are uncoupled from environmental influences. To address this issue, we have designed a new brain-machine-interface for DBS that combines a slow-adaptive circadian-based stimulation pattern with a fast-acting pathway for responsive stimulation, demonstrated here for seizure management. In preparation for first-in-human research trials to explore the utility of multi-timescale automated adaptive algorithms, design and prototyping was carried out in line with ISO risk management standards, ensuring patient safety. The ultimate aim is to account for chronobiology within the algorithms embedded in brain-machine-interfaces and in neuromodulation technology more broadly.