Impact of number of stimulation sites on long-lasting desynchronization effects of coordinated reset stimulation

Abstract

Excessive neuronal synchrony is a hallmark of several neurological disorders, e.g., Parkinson’s disease. An established treatment for medically refractory Parkinson’s disease is high-frequency deep brain stimulation. However, it provides only acute relief, and symptoms return shortly after cessation of stimulation. A theory-based approach called coordinated reset (CR) has shown great promise in achieving long-lasting effects. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites to counteract neuronal synchrony. Computational studies in plastic neuronal networks reported that synaptic weights reduce during stimulation, which may cause sustained structural changes leading to stabilized desynchronized activity even after stimulation ceases. Corresponding long-lasting effects were found in recent preclinical and clinical studies. We study long-lasting desynchronization by CR stimulation in excitatory recurrent neuronal networks of integrate-and-fire neurons with spike-timing-dependent plasticity (STDP). We focus on the impact of the stimulation frequency and the number of stimulation sites on long-lasting effects. We compare theoretical predictions to simulations of plastic neuronal networks. Our results are important regarding CR calibration for two reasons. We reveal that long-lasting effects become most pronounced when stimulation parameters are adjusted to the characteristics of STDP—rather than to neuronal frequency characteristics. This is in contrast to previous studies where the CR frequency was adjusted to the dominant neuronal rhythm. In addition, we reveal a nonlinear dependence of long-lasting effects on the number of stimulation sites and the CR frequency. Intriguingly, optimal long-lasting desynchronization does not require larger numbers of stimulation sites.

Coordinated Reset Vibrotactile Stimulation Induces Sustained Cumulative Benefits in Parkinson’s Disease

“…While intrapopulation synapses typically strengthened during stimulation, interpopulation synapses weakened. Weakening of interpopulation synapses was in accordance with previous results on electrical multisite CR stimulation presented in Kromer et al (2020) . However, results for intrapopulation synapses differed qualitatively.…”

“…During CR stimulation, the former strongly affects interpopulation synapses, whereas the latter dominates the dynamics of intrapopulation synapses ( Kromer and Tass, 2020 ). We expect that qualitatively similar results for interpopulation synapses during vCR and electrical CR stimulation were caused by the characteristic statistics of time lags in the CR pattern, used here and in Kromer et al (2020) . In contrast, individual stimuli used here and in Kromer et al (2020) differed significantly.…”

“…However, results for intrapopulation synapses differed qualitatively. In more detail, Kromer et al (2020) reported a weakening of intrapopulation synapses during electrical CR stimulation. This discrepancy may result from different statistics of neuronal spiking responses to administered stimuli.…”

“…Brain regions possessing excessive neuronal synchrony during PD were modeled using a network of excitatory LIF neurons with STDP ( Kromer and Tass, 2020 ; Kromer et al, 2020 ). Details on the model are given in the Supplementary Material .…”

“…Details on the model are given in the Supplementary Material . Parameters were chosen such that a stable synchronized and a stable desynchronized state coexisted ( Kromer and Tass, 2020 ; Kromer et al, 2020 ). Depending on their initial connectivity, networks approached either the synchronized state (strong initial connectivity) or the desynchronized state (weak initial connectivity) (see Supplementary Material for more details).…”