Abstract
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.
Highlights
Several neurological disorders like Parkinson’s disease (PD), essential tremor, epilepsy or tinnitus are characterized by abnormal neuronal synchronization[1,2,3,4,5,6,7]
Other approaches suggested in the framework of the model-based development of desynchronizing methods are based on feedback techniques, where the mean field of synchronized population is measured, preprocessed and fed back as stimulation signal[46,47,48,49,50,51,52,53,54,55,56], or on the phase response properties of neurons, where the stimulation signal can be derived from the phase response curve (PRC)[57, 58]
We compare the effect of the pulsatile delayed feedback stimulation for different widths of the interphase gap, see Fig. 3B in Methods, when the stimulation is administered to synchronized subthalamic nucleus (STN) neurons only (GPe neurons are not stimulated) whose stimulation-free dynamics is illustrated in Fig. 2 in Methods
Summary
Several neurological disorders like Parkinson’s disease (PD), essential tremor, epilepsy or tinnitus are characterized by abnormal neuronal synchronization[1,2,3,4,5,6,7]. One of the topics of these investigations is to evaluate the optimal shape and timing of the stimulation pulses[19,20,21,22,23,24] This issue is addressed in the present study and will turn out to be key for effective closed-loop desynchronizing stimulation. Another branch of research was devoted to a model-based development of novel stimulation algorithms counteracting abnormal neuronal synchrony by desynchronization[25]. In this study we apply the pulsatile linear as well as nonlinear delayed feedback with and without interphase gap to a physiology-based model network of STN-GPe neurons introduced previously[62, 63] and investigate the resulting desynchronization effects
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