Tass Lab News and Events

Coordinated Reset Stimulation of Plastic Neural Networks with Spatially Dependent Synaptic Connections

In a detailed computational follow up study we analyze the interplay between spatially inhomogeous connectivity patterns and the impact of different types of CR sequences.

Sequences and their shuffling may crucially impact coordinated reset stimulation – A theoretical study

In a Theoretical study we demonstrated that important role of sequences ad their shuffling on the stimulation outcome of coordinated reset stimulation.

Emerging wearable technologies for multisystem monitoring and treatment of Parkinson’s disease: a narrative review

This paper provides a narrative review about emerging wearable technologies for multisystem monitoring and treatment of Parkinson’s disease.

Decoupling of interacting neuronal populations by time-shifted stimulation through spike-timing-dependent plasticity

In this computational study, we tested whether a specific pattern of brain stimulation can decrease pathologically strong inter-population synaptic connectivity through spike-timing-dependent plasticity (STDP). We tested how introducing a time shift between stimuli delivered to two interacting populations of neurons can effectively decouple them. Our results aim to optimize therapeutic multichannel stimulation protocols for the treatment of brain disorders.

Asymmetric adaptivity induces recurrent synchronization in complex networks

This computational study describes the phenomenon of recurrent synchronization in complex dynamical networks with asymmetric adaptivity. The results show how adaptation mechanisms can play a fundamental role for neuronal pattern generators. This mechanism might be relevant for the understanding of the pathophysiology of Parkinsonian resting tremor and other impaired central pattern generators.

Perspectives on adaptive dynamical systems

Adaptivity, i.e. the ability to adapt to changes on various levels, is a key element of living systems and intelligent technical systems. This review covers a variety of research areas focusing on adaptive systems and includes a short review highlighting key principles of coordinated reset stimulation.

Synaptic network structure shapes cortically evoked spatio-temporal responses of STN and GPe neurons in a computational model

We developed a computational model of the STN-GPe circuit, a central part of the BG. We studied how evoked responses are affected by systematic changes in the network structure. To quantify the BG’s organization in the form of functional channels, we suggested a two-site stimulation protocol. Our model reproduced the cortically evoked responses of STN and GPe neurons and the contributions of different pathways suggested by experimental studies. Our two-site stimulation protocol yielded an approximate functional channel width. Our approach enables to assess functional connectivity patterns and may, ultimately, enable to calibrate multichannel stimulation techniques for the therapy of brain disorders.  

How to Use Math and Physics to Treat Parkinson's with a Vibrating Glove

On Nov 21, 2022 it was Peter Tass’ honor and pleasure to give a micro lecture at the Stanford 2022 Reunion’s President’s Welcome and Micro Lectures in Stanford Memorial Auditorium. Stanford Alumni were a fantastic audience!

Synaptic reshaping of plastic neuronal networks by periodic multichannel stimulation with single-pulse and burst stimuli

Our computational study shows that periodic multichannel stimulation may massively reshape synaptic connectivity of neuronal networks by specifically increasing or decreasing different connections, eventually contributing to better brain stimulation methods for functional restoration and achieving long-term therapeutic effects.

To understand the effects of different plasticity mechanisms on brain activity and responses to stimulation, we studied the impact of spike-timing-dependent plasticity (STDP) and structural plasticity on networks of neuronal phase oscillators. Our findings indicate that a network with a combination of STDP and structural plasticity may require stronger and longer stimulation to switch between the states than a network with STDP only. This study was a collaboration with Kanishk Chauhan (https://www.ohio.edu/cas/kc303218 ) and Prof. Alexander Neiman (https://www.ohio.edu/cas/neimana ).

Long-lasting desynchronization of plastic neuronal networks by double-random coordinated reset stimulation

This computational and analytical study shows how to further improve the parameter-robustness of Coordinated Reset (CR) stimulation by introducing strong jitters of stimulus times combined with variations of stimulus amplitudes. This additional algorithmic feature enables CR stimulation effects to be considerably less dependent on adapting stimulation parameters to frequency characteristics of abnormal brain rhythms, especially when using large numbers of stimulation sites. 

Spike-timing-dependent plasticity mediated by dopamine and its role in Parkinson's disease pathophysiology

Theis review paper is focused on the impact of dopamine-induced changes of plasticity mechanisms, in particular, synaptic plasticity in Parkinson’s disease.

Vibrotactile Coordinated Reset Stimulation for the Treatment of Parkinson’s Disease

The Perspective summarizes the development of vibrotactile coordinated reset fingertip stimulation for Parkinson’s therapy and provides an outlook of upcoming studies.

Clinical efficacy and dosing of vibrotactile coordinated reset stimulation in motor and non-motor symptoms of Parkinson’s disease: a study protocol

This paper presents the study protocol of our FDA approval study for vibrotactile coordinated fingertip stimulation for Parkinson’s therapy

Treatment tone spacing and acute effects of acoustic coordinated reset stimulation in tinnitus patients

Acoustic Coordinated Reset (aCR) stimulation is a non-invasive technique for the treatment of chronic subjective tinnitus. aCR uses treatment tones centered around the patient’s dominant tinnitus tone delivered according to the CR algorithm. In this study we investigated how the spacing of the treatment tones impacts on the acute therapeutic effect. More loosely spaced aCR tones (as opposed to densely spaced tones) resulted in a stronger reduction of tinnitus loudness and annoyance scores in the acute stimulation setting.

Long-lasting desynchronization effects of coordinated reset stimulation improved by random jitters

This computational and analytical study shows how to improve the parameter-robustness of Coordinated Reset (CR) stimulation by introducing moderate jitters of stimulus times. This additional algorithmic feature enables CR stimulation effects to be less dependent on adapting stimulation parameters to frequency characteristics of abnormal brain rhythms. 

Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity

In this computational paper we address an important and clinically relevant issue: So far, all our mathematical models used to develop Coordinated Reset (CR) stimulation were not able to explain why the efficacy of vibrotactile CR stimulation (“glove” therapy) for the treatment of Parkinson’s disease or acoustic CR stimulation for the treatment of tinnitus increases in the course of the treatment. Specifically, for both conditions we observe that in the course of the CR therapy the required dosage decreases. By only taking into account synaptic plasticity (i.e. STDP = spike-timing-dependent plasticity), we were not able to explain this phenomenon. However, by taking into account both synaptic and homeostatic structural plasticity, we observe this very phenomenon. Synaptic plasticity is governed by how pairs of synaptically connected neurons interact: This type of plasticity adapts the strength of synapses to the corresponding neurons’ activity. In contrast, homeostatic structural plasticity focusses on the single neuron: Structural plasticity is a homeostatic process that keeps neuronal firing rates within biologically reasonable ranges and adapts the amount of synapses accordingly.

Intriguingly, pauses in between therapy sessions play an important role, enabling the therapeutic effect of CR stimulation to unfold. This study (and subsequent computational studies) will help us to generate detailed and testable hypotheses for optimal dosing regimens for clinical trials.

This study was done in collaboration with Prof. Thanos Manos (Laboratoire de Physique Théorique et Modélisation, CNRS, UMR 8089, CY Cergy Paris Université, Cergy-Pontoise Cedex, France) and Dr. Sandra Diaz-Pier (Simulation & Data Lab Neuroscience, Institute for Advanced Simulation, Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH, JARA, Jülich, Germany).

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

In this pilot feasibility study we investigate clinical and electrophysiological effects of months-long vibrotactile Coordinated Reset (CR) stimulation delivered to the fingertips through a glove system with vibratory stimulators attached to the fingertips. This therapy employs weak, non-painful vibrations and is a completely non-invasive treatment. We revealed clinically and statistically significant effects combined with a significant reduction of Parkinson’s-related synchronized activity in the sensorimotor cortex revealed by electroencephalography (EEG) recordings. In addition, in this paper we provide technical details of our glove treatment together with the computation foundation of our therapeutic approach.

Multistability in a star network of Kuramoto-type oscillators with synaptic plasticity

Neural networks with synaptic plasticity can attain very different regimens, for instance, “pathological” states with abnormally strong synchronized activity and abnormally strong synaptic connections or “physiological” states with desynchronized activity and weaker synaptic connections. Since appropriate stimulus patterns may move neural networks from “pathological” to “physiological” states, it is important to understand how qualitatively different network states evolve. In this study we investigate the emergence of fundamental connectivity patterns in plastic neural networks.    

Accumbens coordinated reset stimulation in mice exhibits ameliorating aftereffects on binge alcohol drinking

In a mouse model for binge drinking we demonstrate that electrical Coordinated Reset (CR) stimulation delivered through implanted electrodes to the nucleus accumbens during only the initial phase of exposure to alcohol and prior to the exposure significantly reduces binge-like drinking without interfering with social behavior or locomotor activity. This is the first study where CR stimulation was delivered in a preventive manner. 

A Single Case Feasibility Study of Sensorimotor Rhythm Neurofeedback in Parkinson’s Disease

The sensorimotor rhythm (SMR) is a brain wave which can be recorded over the sensorimotor cortex and typically appears in oscillatory spindles. Healthy subjects can self-regulate their SMR rhythm when provided adequate feedback, e.g., of the SMR amplitude. This procedure is called SMR neurofeedback. In this pilot study, we demonstrated that SMR neurofeedback could be performed in a Parkinson’s patient. Our results provide first evidence for the feasibility of SMR neurofeedback training as an adjunct non-invasive therapy for reducing Parkinson’s disease related activity and upregulating SMR in the human motor cortex.

Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation

In this computational study we introduce a double-random stimulation technique, called random reset (RR) stimulation, where stimuli are delivered at randomly selected stimulation sites at random sites to neural networks with synaptic plasticity. RR stimulation reduces abnormally strong synaptic connections which, in turn, leads to a long-lasting desynchronization. Put otherwise, RR stimulation causes the neural networks to unlearn strong synaptic connections, thereby losing the ability to generate overly synchronized activity. Remarkably, RR does not require large spatial resolution, i.e., separate delivery through a larger number of stimulation contacts. In fact, RR stimulation with low spatial resolution performs even better at low stimulation amplitudes.  

Technology of deep brain stimulation: current status and future directions

Deep brain stimulation (DBS) is a neurosurgical procedure that involves the implantation of a neurostimulator and depth electrodes. The neurostimulator is a medical device which delivers electrical impulses through implanted depth electrodes to specific targets in the brain for the treatment of movement disorders, such as Parkinson's disease, essential tremor, and dystonia, as well as other disorders, such as obsessive-compulsive disorder and epilepsy. This review provides a comprehensive overview of the technical development of DBS, ranging from its origins to potential future advancements.

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

Modern depth electrodes for deep brain stimulation enable to stimulate multiple parts of the surrounding issue through a number of stimulation contacts. Given we understand the anatomical location of a depth electrode relative to the actual target area, we have to determine the number of stimulation contacts for CR stimulation. In this computational study we analyzed the dependence of long-lasting CR desynchronizing effects on the number of stimulation sites and the stimulation frequency. Surprisingly, we revealed that long-lasting effects become most pronounced when stimulation parameters are adjusted to the characteristics of synaptic plasticity — rather than to neuronal frequency characteristics. In addition, we show that optimal long-lasting desynchronization does not require larger numbers of stimulation sites. In fact, only a few stimulation sites might be sufficient.

Entrainment of a network of interacting neurons with minimum stimulating charge

To avoid damage to neuronal tissue, it is important to stimulate neuronal tissue at minimum absolute values of the stimulating current. Several applications require to deliver periodic pulse trains which entrain neuronal populations, i.e. force the neuronal populations to discharge in synchrony with the delivered pulse train. With techniques from theoretical physics and biophysics, we have derived a general expression for the optimal stimulation waveform, which provides an entrainment of a neural network to the stimulation frequency with a minimum absolute value of the stimulating current. This is to fulfill the minimum-charge condition which aims at reducing damage to neural tissue.

Long-lasting desynchronization by decoupling stimulation

Many studies have been devoted to the development of stimulation techniques counteracting excessive neuronal synchrony. In order to target the underlying cause of strong synchrony, we present a novel approach: decoupling stimulation. Analyzing the decoupling potential of different stimulation patterns, we present a random reset stimulation algorithm which induces parameter-robust long-lasting desynchronization that persists after cessation of stimulation.

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

In a computational study we combined auditory filter theory and acoustic Coordinated Reset (CR) neuromodulation technology and introduced equivalent rectangular filter-based acoustic CR neuromodulation. This method was designed to specifically counteract abnormal neuronal synchronization, e.g., in patients with chronic subjective tinnitus.

Adaptive delivery of continuous and delayed feedback deep brain stimulation - a computational study

In a computational study we introduce a novel type of adaptive deep brain stimulation: adaptive pulsatile linear delayed feedback stimulation. This stimulation method was designed to specifically counteract abnormal neuronal synchronization as found in a number of brain disorders, e.g. Parkinson’s disease.

Department of Neurosurgery

The Tass Lab is part of the Department of Neurosurgery.