Noninvasive Brain Stimulation Lab (NBS-Lab)

The transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique which employs low electrical currents.

By placing at least two electrodes on the head, the patient receives either an anodal or cathodal stimulation which, repsectively, lead to an increase or decrease of the cortical excitability (tDCS Database: http://tdcsdatabase.com/; Developed by the research group in cooperation with the research group surrounding Prof. Marom Bikson).

Already a short stimulation duration (~10 min) can have positive effects. These effects are due to electrophysiological changes in the neuronal cell membrane.

Higher performance in various cognitive areas (e.g. memory, attention, reaction time) can be achieved through the stimulation. Depending on the stimulation protocol these effects can even persist after the simulation has been discontinued.

Currently, we are researching the efficacy of tDCS in cancer-related pain and its combined effect with task training to improve dual task ability in the healthy elderly.

The transcranial alternating current stimulation (tACS) differs from tDCS as it applies a low-intensity sinusoidal electrical current to the brain. This occurs at a chosen frequency to interact with the brain’s cortical oscillations which can change the excitability or activity in specific brain areas.

Both single-frequency and cross-frequency tACS paradigms exist. The latter is based on the superposition of a high-frequency signal with a low-frequency signal using phase-amplitude coupling.

Like tDCS, tACS offers many opportunities to be applied. Currently, the NBS lab is applying tACS to older adults to improve their cognitive abilities and prevent neurocognitive disorders such as mild cognitive impairment, a precursor to dementia. We are also testing the efficacy of tACS to reduce pain in patients with cancer as well as to improve the visual functioning of patients with significant optic atrophy caused by glaucoma.

The transcranial random noise stimulation (tRNS) employs electrical currents which are randomized in terms of their frequency and amplitude. This technique allows for the enhancement of neural excitability. The underlying mechanisms are yet to be understood.

Explanations for the efficacy of the tRNS approach are based on the interference with cortical rhythms, plasticity changes or the improvement of the signal-to-noise ratio (SNR) which can lead to improved sensibility.

Future research of our lab will tap into the efficacy of tRNS for the treatment of various cognitive diseases.

The transcranial magnetic stimulation (TMS) utilizes strong magnetic fields to stimulate the brain non-invasively. The magnetic field induces an electrical current in the brain which can increase or decrease the cortical excitability.

In contrast to the transcranial electrical stimulation (TES) TMS can depending on the intensity of the stimulation directly trigger action potentials, or inhibit them by creating a silent period.

TMS can also be used as a diagnostic tool on the motor cortex to investigate motor evoked potentials (MEP). MEP can serve as an indication for brain or spinal cord injuries (e.g. multiple sclerosis).

TMS or repetitive TMS (rTMS) is used as a therapeutic to causes persistent changes in the activity of the cortex. This allows for the treatment of various diseases, e.g. depression.

Currently, we are investigating the potential cognitive benefits of fronto-vagal rTMS in the healthy elderly and its impact on the interaction between the heart and the brain.

Description:

This study represents a novel attempt to enhance cognitive aging by integrating the emerging field of heart-brain interaction. Heart rate variability (HRV) serves as a crucial index of heart-brain interaction and autonomic nervous system dynamics. Previous research has established a positive association between higher HRV and enhanced functional connectivity in the medial prefrontal cortex and amygdala, accompanied by improved cognitive performance. Non-invasive brain stimulation, particularly transcranial magnetic stimulation (TMS), holds significant potential for improving cognitive function in individuals with cognitive impairment. Recent studies have revealed that applying repetitive TMS (rTMS) over the frontal-vagal network can enhance HRV. Therefore, our aim is to enhance cognitive performance in subjects with cognitive impairment and normal aging through frontal-vagal rTMS. Furthermore, we aim to explore the underlying mechanisms of heart-brain interaction during aging using brain imaging techniques.

• Responsible for the study: Ms. Xue Guo
• E-Mail: : Xue.Guo(at)med.uni-goettingen.de
• Collaborating partners:
  • Prof. Melanie Wilke, Dept. of Cognitive Neurology, University Medical Center Göttingen

(BMBF: Miteinander durch Innovation 16SV9248)

Based on the results of a previous study (Means to improve cognition in older adults with or without cognitive impairment - from training to non-invasive brain stimulation, see below), this project aims to combine tES with cognitive training to improve the cognitive abilities of older people. For this purpose, a cognitive training in virtual reality is developed in this study, which is specially adapted to the needs of older adults. In addition, this training is adaptively adjusted to the individual cognitive strain, which is measured by means of eye tracking during the VR application, in order to achieve an optimal learning effect. The exact stimulation location is also individually adapted to the anatomy of the individual (using MRI images and simulations of the propagation of the electric field strength). Various cognitive parameters (memory, executive functions) and electrophysiological data (EEG) are examined. The aim is to achieve a lasting improvement in the cognition of older people.

The project is led by Irina Shiyanov, CEO of the VRalive UG, a start-up company specialized in VR technology.

• Responsible for the study:Dr. Lukas Diedrich (PostDoc)
• Collaborating company: VRalive UG Braunschweig (CEO Irina Shiyanov)
• Link to project: https://www.interaktive-technologien.de/projekte/neurovr-plus

We have already successfully validated and established the method of noninvasively deriving motor evoked potentials of the diaphragm (diMEPs) by means of TMS in our institution (Chakalov et al., 2022). TMS allows noninvasive and non-volitional inspection of the integrity of the corticospinal pathway to breathing muscles. Therefore, a currently ongoing project aims to use this method for diagnosing diaphragm dysfunction in ventilated critically ill patients in the Intensive Care Unit at UMG.

• Responsible for the study: Dr. Ivan Chakalov
• Collaborating partners: Dr. Caspar Stephani, Dept. of Anesthesiology, University Medical Center Göttingen
• Link to relevant publications: The role of the TMS parameters for activation of the corticospinal pathway to the diaphragm

With aging, dual task (DT) ability declines and is more cognitively demanding than single tasks. It has been identified that attention as well as execution factors are the most critical predictors of DT performance, and aging-induced decline in these factors is closely related to the impaired cognition in the elderly. Previous studies addressed the rapidly declining DT performance as a predictor of neurodegenerative disease including Parkinson’s disease and Alzheimer’s disease. The purpose of this study is to explore the effects of theta tACS and anodal tDCS on gait and cognitive performance, we are implementing a neuromodulation-based method to improve dual-task performance in the healthy elderly. 

• Responsible for the study: Mr. Yong Jiang
• Contact for interested participants:
  • Tel: 0551- 3968474
  • Contact hours: Montag & Mittwoch,13.00-15.00 Uhr
  • E-mail address: neurologie.multitasking(at)med.uni-goettingen.de

Glaucoma is one of the most common causes of blindness and affects more than 70 million people worldwide. It is characterized by the loss of retinal ganglion cells associated with a progressive optic neuropathy resulting in an impairment of visual function, e.g. visual field loss.

To date, glaucoma can only be treated by lowering intraocular pressure to slow down the progressive course of the disease. Indeed, the underlying mechanisms are not targeted by the current treatment strategies, and vision loss, once present, cannot be restored. Therefore, new treatment options are required to improve vision as the nerve fibre loss, once it is manifest, is not reversible, neither by medication nor by surgical approach.

In several small trials and one multicenter study, tACS was performed daily in an attempt to re-activate residual vision in optic neuropathy using frequencies ranging from theta to high beta via electrodes placed near the eye. The treatment increased light detection performance and reduced patient-reported, vision-related daily living impairments that correlated moderately with visual field gains.  However, the level of evidence of this method is still poor, and further trials are necessary. In the opinion of German ophthalmological societies (i.e.DOG and BVA), the applied methods were not satisfactory (e.g. non-established perimetry methods, lack of the measurements of eye movements, inhomogeneous patient populations, and incorrectly defined trial endpoints (http://www.dog.org).

Our multi-center double-blind sham-controlled study aims to clarify the contradictory data in this field and uses established and well-defined visual-field parameters. The novel aspects of this trial are the individual current flow modeling based on the visual impairment and the application of stimulation protocol with predefined electrode montage and fixation of a target during the experiment.

• Responsible for the study in the Neurology: Prof. Andrea Antal
• Responsible for the study in the Ophthalmology: Prof. M. Schittkowski & Dr. J. Pohlner, University Medical Center Göttingen

PAINLESS: Home-based transcranial electrical stimulation in for pain relief in patients with cancer.

(Europe Horizon: HORIZON-HLTH-2021-DISEASE-04-01; PAINLESS)

A new home-based approach to manage pain in patients with cancer is being investigated in a multicenter clinical trial using transcranial electrical stimulation (tDCS and tACS). The study aims to test the therapeutic efficacy of these methods (15-days of daily tES) in pain relief and reduction of associated symptoms in patients with cancer. The mechanistic impact of the stimulation interventions will also be assessed via quantitative sensory testing and EEG. Moreover, we will compare how cancer patients with pain and without pain differ in terms of pain processing using central biomarkers of pain. Having a home-based intervention improves the accessibility of the study to patients living far away as well as reduces the burden of daily travels to the clinic.

This study is part of the EU research and innovation funding project Europe Horizon. In total, ten different countries cooperate on this study.

• Responsible for the study: Perianen Ramasawmy
• Collaborating partners:
  • Projected led by Prof. Maria Teresa Carrilla-de-la-Peña, University Santiago de Compostela.
• Link to project: https://palliativeprojects.eu/painless/home/about-painless/
• Contact for interested participants:
  • E-mail address: neurologie.painless(at)med.uni-goettingen.de
  • Tel: 0551- 3968474
  • Contact hours: Tuesday & Thursday, 10.00-12.00 Uhr

This study aimed to investigate the effects of combined transcranial electrical stimulation and computerized cognitive training to improve cognitive abilities in older adults with or without cognitive impairment. Mild cognitive impairment is associated with an increased risk of developing dementia, which underscores the urgency for early diagnosis and the development of innovative treatment modalities.

• Responsible for the study: Dr.Lukas Diedrich
• Collaborating partners: Prof. Michal Lavidor, Department of Psychology, Bar Illan University Israel
• Links to publications:
  • Boosting working memory in the elderly: driving prefrontal theta–gamma coupling via repeated neuromodulation
  • Prefrontal theta—gamma transcranial alternating current stimulation improves non-declarative visuomotor learning in older adults
  • New Methods, Old Brains—A Systematic Review on the Effects of tDCS on the Cognition of Elderly People
  • Beyond social engagement: cognitive training leads to greater cognitive improvement in older adults

The study aimed to test the therapeutic and mechanistic effects of combining mindfulness meditation and transcranial direct current stimulation in fibromyalgia patients who received a brief 4-week mindfulness training. Fibromyalgia is a chronic pain condition characterized by widespread and persistent musculoskeletal pain. This condition is also associated with sleep, cognitive, mood, and psychological impairments as well as chronic fatigue. Mindfulness meditation is a cognitive training technique in which the practitioner focuses on awareness of sensations, emotions and thoughts without pursuing them further. We investigated the underlying mechanisms in the cortex of our novel combination method using transcranial magnetic stimulation and EEG.

• Responsible for the study: Dr. Perianen Ramasawmy
• Collaborating partners: Prof. Frank Petzke, Department of Anesthesiology, University Medical Center Göttingen & Dr. Olga Lucia Gamboa Arana, EQness, Sydney, Australia
• Links to publications: 
  • Pain reduction in fibromyalgia syndrome through pairing transcranial direct current stimulation and mindfulness meditation: A randomized, double-blinded, sham-controlled pilot clinical trial
  • Stimulated brains and meditative minds: A systematic review on combining low intensity transcranial electrical stimulation and meditation in humans

Background:

Non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) have received a great deal of attention in recent years in research and for the treatment of mental illnesses. In addition, they are being used more and more frequently. As a result, numerous safety guidelines have been established to ensure the safe use of these methods in research and clinical treatment. However, there are ethical questions for researchers and practitioners in this context that are difficult to answer; for example:

Where is the line between treatment and performance enhancement?

How should vulnerable groups such as the elderly or children be treated?

Should brain stimulation be used for individuals who are unable to consent due to illness?

What might be the impact of research results outside of clinical research and treatment on the open market?

In addition, more and more devices and instructions for the use of the underlying technology have been developed in the recent past. These are intended to be used for non-clinical application purposes such as cognitive performance enhancement and their effectiveness is often not scientifically proven.

Aim:

The project aimed to develop a Code of Conduct for the use and research of non-invasive brain stimulation for the European Union together with representatives from society, science, politics and industry. This code of conduct should enable researchers to reflect on their own research from an ethical point of view and support legislative bodies in developing a long-term legal framework for the use and marketing of non-invasive brain stimulation.

Procedure:

After a comprehensive literature review, the perspectives of everyday experts was collected in participatory workshops including different stakeholders, which will then be discussed with experts from different relevant disciplines. On the basis of these participatory results, a code of conduct was developed that can take the different perspectives into account.

https://www.cerri.iao.fraunhofer.de/de/projekte/stimcode.html

• Responsible for the study: Prof. Andrea Antal and Dr. Perianen Ramasawmy
• Collaborating partners:Project led byDr. Moritz Julian Maier, Fraunhofer IAO
• Link to publications:  
  • STIMCODE
  • Recommendation for the use and development of non-invasive brain stimulation— insights from a trans-European participatory stakeholder study

Although modulatory effects of temporal interference stimulation (TIS) have been demonstrated in the brain of animals and in human models, the strategy is not yet proved in living humans. In this study, we are trying to build evidence for the concept first through simple protocols testing its elementary mechanisms in the muscle. After completion of analysis on healthy individuals, patients affected with different neuromuscular diseases are included. Compliance in the use of the method in patients with a pre-damaged neuromuscular unit are evaluated. In addition, differences in response of individuals with neuropathic or myopathic disease are  compared to healthy controls.

• Responsible for the study: Mr. Simon Gronemann & Mr. Krisztian Iszak
• Collaborating partners: Dr. Jana Zschüntzsch, Dept. of Neurology, University Medical Center Göttingen.
• Link to publications: 
  • Why Temporal Inference Stimulation May Fail in the Human Brain: A Pilot Research Study