Oleksandr V. Popovych

Effectively desynchronizing deep brain stimulation based on a coordinated delayed feedback stimulation via several sites: a computational study

In detailed simulations we present a coordinated delayed feedback stimulation as a particularly robust and mild technique for desynchronization. We feed back the measured and band-pass filtered local filed potential via several or multiple sites with different delays, respectively. This yields a resounding desynchronization in a naturally demand-controlled way. Our novel approach is superior to previously developed techniques: It is robust against variations of system parameters, e.g., the mean firing rate. It does not require time-consuming calibration. It also prevents intermittent resynchronization typically caused by all methods employing repetitive administration of shocks. We suggest our novel technique to be used for deep brain stimulation in patients suffering from neurological diseases with pathological synchronization, such as Parkinsonian tremor, essential tremor or epilepsy.

Coordinated reset neuromodulation for Parkinson's disease: proof-of-concept study.

The discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinsons disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony.

Unlearning tinnitus-related cerebral synchrony with acoustic coordinated reset stimulation: theoretical concept and modelling

Tinnitus is a deafferentation-induced phantom phenomenon characterized by abnormal cerebral synchrony and connectivity. Computationally, we show that desynchronizing acoustic coordinated reset (CR) stimulation can effectively counteract both up-regulated synchrony and connectivity. CR stimulation has initially been developed for the application to electrical deep brain stimulation. We here adapt this approach to non-invasive, acoustic CR stimulation. For this, we use the tonotopic organization of the central auditory system and replace electrical stimulation bursts applied to different brain sites by acoustically delivered tones of different pitch. Based on our simulations, we propose non-invasive acoustic CR stimulation as a possible novel therapy for tinnitus.

Desynchronizing anti-resonance effect of m: n ON–OFF coordinated reset stimulation

This computational study is devoted to the optimal parameter calibration for coordinated reset (CR) stimulation, a stimulation technique suggested for an effective desynchronization of pathological neuronal synchronization. We present a detailed study of the parameter space of the CR stimulation method and show that CR stimulation can induce cluster states, desynchronization and oscillation death. The stimulation-induced cluster states (at CR offset) cause the longest desynchronizing post-stimulus transients, which constitute an essential part of the CR stimulation effect. We discover a desynchronization-related anti-resonance response of the stimulated oscillators induced by a periodic ON-OFF CR stimulation protocol with m cycles ON stimulation followed by n cycles OFF stimulation. The undesired collective oscillations are effectively desynchronized if the stimulation is administered at resonant frequencies of the controlled ensemble, which is in complete contrast to the typical effect of the usual periodic forcing.

Delayed feedback control of synchronization in locally coupled neuronal networks

We present a novel, particularly robust technique for effective desynchronization of neuronal populations in the presence of noise. Delayed feedback signals are administered in a spatially coordinated way via four stimulation sites using different delays for each stimulation site, respectively. The technique is numerically tested in a phase oscillator model and in a physiologically realistic model. We propose our methods as novel, particularly mild and effective stimulation protocols for the therapy of patients suffering from Parkinsons disease, essential tremor or epilepsy.

Desynchronizing the abnormally synchronized neural activity in the subthalamic nucleus: a modeling study

A mathematical model of a target area for deep brain stimulation was used to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. In total, three newly developed stimulation techniques based on multisite coordinated reset and delayed feedback were tested and compared with a high-frequency stimulation method that is currently used as a standard stimulation protocol for deep brain stimulation. By modeling both excitatory and inhibitory actions of the electrical stimulation, we revealed the desynchronization impacts of the novel stimulation techniques. This contrasts with standard high-frequency stimulation, which failed to desynchronize the target population and whose inhibitory effects blocked all neuronal activity. We also explored the demand-controlled character of the proposed methods, and demonstrated that the amount of stimulation current required was considerably smaller than that for high-frequency stimulation. These novel stimulation methods appear to be superior to standard high-frequency stimulation techniques, and we propose the methods now be used for deep brain stimulation.

Self-organized noise resistance of oscillatory neural networks with spike timing-dependent plasticity

Intuitively one might expect independent noise to be a powerful tool for desynchronizing a population of synchronized neurons. We here show that, intriguingly, for oscillatory neural populations with adaptive synaptic weights governed by spike timing-dependent plasticity (STDP) the opposite is true. We found that the mean synaptic coupling in such systems increases dynamically in response to the increase of the noise intensity, and there is an optimal noise level, where the amount of synaptic coupling gets maximal in a resonance-like manner as found for the stochastic or coherence resonances, although the mechanism in our case is different. This constitutes a noise-induced self-organization of the synaptic connectivity, which effectively counteracts the desynchronizing impact of independent noise over a wide range of the noise intensity. Given the attempts to counteract neural synchrony underlying tinnitus with noisers and maskers, our results may be of clinical relevance.

Macroscopic entrainment of periodically forced oscillatory ensembles.

Large-amplitude oscillations of macroscopic neuronal signals, such as local field potentials and electroencephalography or magnetoencephalography signals, are commonly considered as being generated by a population of mutually synchronized neurons. In a computational study in generic networks of phase oscillators and bursting neurons, however, we show that this common belief may be wrong if the neuronal population receives an external rhythmic input. The latter may stem from another neuronal population or an external, e.g., sensory or electrical, source. In that case the population field potential may be entrained by the rhythmic input, whereas the individual neurons are phase desynchronized both mutually and with their field potential. Intriguingly, the corresponding large-amplitude oscillations of the population mean field are generated by pairwise desynchronized neurons oscillating at frequencies shifted far away from the frequency of the macroscopic field potential.

Variability of spatio-temporal patterns in non-homogeneous rings of spiking neurons

We show that a ring of unidirectionally delay-coupled spiking neurons may possess a multitude of stable spiking patterns and provide a constructive algorithm for generating a desired spiking pattern. More specifically, for a given time-periodic pattern, in which each neuron fires once within the pattern period at a predefined time moment, we provide the coupling delays and/or coupling strengths leading to this particular pattern. The considered homogeneous networks demonstrate a great multistability of various travelling time- and space-periodic waves which can propagate either along the direction of coupling or in opposite direction. Such a multistability significantly enhances the variability of possible spatio-temporal patterns and potentially increases the coding capability of oscillatory neuronal loops. We illustrate our results using FitzHugh-Nagumo neurons interacting via excitatory chemical synapses as well as limit-cycle oscillators.

DESYNCHRONIZATION AND DECOUPLING OF INTERACTING OSCILLATORS BY NONLINEAR DELAYED FEEDBACK

A novel control method for desynchronization of strongly synchronized populations of interacting oscillators is described. We show that an ensembles mean field, nonlinearly processed and fed back into the ensemble, causes an effective desynchronization. The method is mild, demand controlled, and robust against system and stimulation parameter variations. The desynchronization and decoupling effects of the method are illustrated by examples of one and two interacting populations of limit-cycle oscillators. We suggest our method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization.