Closed-loop deep brain stimulation by pulsatile delayed feedback with increased gap between pulse phases.

Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals. In this way we combine the desynchronizing delayed feedback approach with the HF DBS technique. We show that such a pulsatile delayed feedback stimulation can effectively and robustly desynchronize a network of model neurons comprising subthalamic nucleus and globus pallidus external and suggest this approach for desynchronizing closed-loop DBS. Intriguingly, an interphase gap introduced between the recharging phases of the charge-balanced biphasic pulses can significantly improve the stimulation-induced desynchronization and reduce the amount of the administered stimulation. In view of the recent experimental and clinical studies indicating a superiority of the closed-loop DBS to open-loop HF DBS, our results may contribute to a further development of effective stimulation methods for the treatment of neurological disorders characterized by abnormal neuronal synchronization.