Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

Abstract

A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR) stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates) but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on our computational findings we propose a multichannel sham (i.e., inactive) stimulation protocol as control condition for phase 2 and phase 3 studies with desynchronizing multichannel stimulation techniques.

Acoustic coordinated reset therapy for tinnitus with perceptually relevant frequency spacing and levels

“…In these computational-based studies equally spaced linear 39,45,53 , circular 15,16,54,55 or rectangular 13,14,40,47–51 arrangements of the stimulation sites were used. The sub-populations, stimulated by the different stimulation sites, either did not overlap at all 13,45 , or their overlap depended on stimulation amplitude, spatial arrangement of stimulation sites and spatial stimulation profile 13–16,39,40,46–58 . To this end, different stimulation profiles were used to model current spread in brain tissue caused by electrical stimulation 59,60 .…”

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

“…In the present paper, we explored vCR stimulation as treatment for PD. Three different stimulation patterns were considered: regular vCR ( Tass, 2017 ), the novel noisy vCR, and purely periodic multichannel stimulation (PPMS) ( Zeitler and Tass, 2018 ). Patients in study 1 were stimulated using the noisy vCR pattern and patients in study 2 using either the regular vCR or the noisy vCR pattern.…”

“…Finally, we compared results for regular and noisy vCR stimulation to vPPMS as presented by Zeitler and Tass (2018) . The latter is illustrated in Figure 1C .…”

“…The latter is illustrated in Figure 1C . In contrast to vCR stimulation, vPPMS considers simultaneous stimulation of all fingertips and does not enforce phase shifts between the spiking activity of individual neuronal subpopulations ( Tass, 2003 ; Zeitler and Tass, 2018 ). We therefore hypothesized poor performance with respect to long-lasting desynchronization effects.…”

Long-lasting desynchronization by decoupling stimulation

“…To enhance long-lasting desynchronization effects, a series of computational studies focused on modifying the sequence by which stimuli are delivery to different stimulation sites. For this, rapidly or slowly varying CR sequences [70,76], periodic flashing sequences [101] as well as various stochastic versions thereof [102] were used. Recently, it was also suggested to de-liver neuron-type specific stimuli in order to induce a constant time shift between spikes of excitatory and inhibitory neurons as STDP would lead to a modulation of the synaptic coupling between both types of neurons and thereby lead to transitions between desynchronized and synchronized states [103].…”