Noninvasive Brain Stimulation Lab (NBS-Lab)

Prof. Dr. Andrea Antal’s research group investigates the effects of non-invasive brain stimulation. This includes the application of transcranial alternating and direct stimulation, as well as the transcranial magnetic stimulation.

With this methodology a range of diseases which originate in the brain can be treated, e.g.: Depression, dementia and fibromyalgia. For the treatment small electrical currents are used to target specific brain areas or related neuronal networks. The stimulation alters the neuronal activity and aims at facilitation or inhibition of brain area.

Research Group

Next to apl. Prof. Dr. Andrea Antal three postdoctoral researcher, five PhD students and two student research assistants who works on the above mentioned projects. In addition, two master students and more than ten medicine students who are being supervised by Prof. Antal for their doctoral thesis are part of our group.

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Research focus

Transcranial direct current stimulation

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 combined effect of mindfulness training and tDCS to treat chronic pain (Fibromyalgia).

Transcranial alternating current stimulation

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.

In addition to changes of the frequency band, a modification of amplitude is possible where a high-frequency signal is being modulated by a low-frequency oscillation (e.g. theta-gamma-coupling).

Like tDCS, tACS offers many opportunities to be applied. Currently, the NBS lab is treating cognitive impairments (e.g. mild cognitive impairment (MCI), a prior of dementia) with the help of tACS.

Transcranial random noise stimulation

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.

Transcranial magnetic stimulation

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, the NBS lab investigates how MEPs in the diaphragm can be elicited and measured. These MEPs could be key to the improvement of the weaning process of patients suffering from breathing muscle deficiencies. TMS would be an opportunity to evaluate corticospinal connections to the breathing muscles even in a sedated state. Our aim is to employ TMS-induced MEPs as a variable to predict weaning success (Dr. Ivan Chakalov und PD Dr. med. Caspar Stephani).

Current studies at the NBS lab

Means to improve cognition in healthy elderly and patients with mild cognitive impairment - from training to non-invasive brain stimulation

Description:

The purpose of this study is to test the effects of a combination treatment of transcranialelectrical stimulation and cognitive training on the cognitive abilities of elderly subjects with mild cognitive impairment compared to healthy subjects. Mild cognitive impairment is associated with an increased risk of developing dementia. Therefore, early diagnosis and intervention seems to be useful.

Cognitive abilities will be tested and compared before the start of stimulation, after the end of the stimulation phase (16 stimulations during 6 weeks) and 18 weeks later.

Fibromyalgia syndrome and direct current stimulation

A new approach to the treatment of fibromyalgia is being investigated in a clinical trial at the Department of Neurology at the University Medical Center Göttingen (UMG) in collaboration with the Pain Medicine Department of the Department of Anesthesiology at UMG. The study aims to strengthen and consolidate the therapeutic effects of electrostimulation treatment in fibromyalgia. To do so, the new study combines transcranial direct current stimulation and mindfulness meditation. Mindfulness meditation is a cognitive training technique in which the practitioner focuses on awareness of sensations, emotions and thoughts without pursuing them further. Previous studies have shown that regular practice of mindfulness meditation reduces the intensity and discomfort of fibromyalgia pain.

The research group is led by Prof. Andrea Antal, M.D., of the Department of Neurology, UMG, and Prof. Frank Petzke, M.D., chief of pain medicine in the Department of Anesthesiology, UMG.

For more information about the study or if interested in participating, participants between the ages of 30 and 75 who have been diagnosed with fibromyalgia syndrome can contact the study director directly.

Breathing and TMS

By comparing the motor responses of the diaphragm after monophasic and biphasic single-pulse TMS within the same group of healthy subjects we demonstrated (Chakalov et al., 2022) that biphasic pulses are more effective in inducing motor responses in this visceral muscle. Overall, the results we obtained suggest that the choice of the TMS-stimulus modality may have a significant impact on the inspection of the corticospinal pathway to diaphragm.

Based on our first experiment, in a current study we are using biphasic TMS to stimulate the diaphragm in patients on mechanical ventilation (still in coma, mainly as a result of severe COVID-19 infection), in the ICU at the UMG, in order to probe the hypothesis that it would be possible to reactivate a spontaneous breathing and/or at least to trigger the ventilator via transcranial magnetic stimulation over the cortical representation of the diaphragm. The main investigator is Dr. Ivan Chakalov.

Temporally interfering alternating current stimulation of the muscles of human subjects

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.

The main investigator ist:

  • Simon Gronemann

Supervisors are:

  • PD Dr. med. Jana Zschüntzsch
  • Dr. med. Stefanie Meyer
  • Prof. Andrea Antal

Differential tDCS and tACS effects on motor and cognitive performance in the healthy elderly

The purpose of this study is to explore the effects of theta-gamma tACS and anodal tDCS on gait and cognitive performance. In addition, a strategy to improve dual-task performance in the healthy elderly is being developed.

The main investigator is:

  • Yong Jiang.

Brain Stimulation Reconsidered - Participative Development of a Code of Conduct for the European Union

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 aims 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 will be collected in several workshops, which will then be discussed with experts from different relevant disciplines. On the basis of these participatory results, a code of conduct will be developed that can take the different perspectives into account.

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

Transorbital electrical stimulation to improve the visual functioning of patients with significant optic atrophy caused by primary open anlge-glaucoma

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 (Crabb 2016).

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, rtACS 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 the patient-reported, vision-related daily living impairments that correlated moderately with visual field gains.  However, the level of evidence of this method is still fairly 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.

This study takes place in cooperation with the Eye clinic at the UMG (Prof. M. Schittkowski, Dr. J. Pohlner).

Central pain modulation biomarkers and their role in the home-based brain stimulation to treat refractory cancer pain

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

The general aim of this study is to improve the understanding of the central mechanisms involved in cancer pain and to use this knowledge to develop and test a home-based neuromodulation treatment for pain care in patients with cancer. First, we will assess the central biomarkers of pain (comparing patients with pain and without pain) and we will create a database with this information. Subsequently, we will design and adapt a wireless transcranial brain stimulator and we will assess its therapeutic efficacy as a treatment for cancer pain.

This study is part of the EU research and innovation funding project Europe Horizon. In total ten different countries cooperate on this study. The project is being led from the university Santiago de Compostela by Prof. Maria Teresa Carrilla-de-la-peña.

Kooperationen

  • Prof. Michal Lavidor, Department of Psychology, Bar Ilan Universität Israel
  • Prof. Dr. Christine von Arnim, Geriatric department, UMG
  • Prof. Dr. Michael Schittkowski, Eye Clinic, UMG
  • Prof. Dr. Frank Petzke, Anesthesia, UMG
  • Dr. Roberto Goya-Maldonado, Inst. for Psychiatry, UMG
  • Prof. Ivana Rosenzweig, Head, Sleep and Brain Plasticity Centre, Department of Neuroimaging, IoPPN, King’s College London, UK
  • Prof. Dezso Nemeth, Lyon Neuroscience Research Center, Université Claude-Bernard Lyon, France
  • Prof. Gyula Kovacs, Biological Psychology and Cognitive Neurosciences, Institute of Psychology, Friedrich-Schiller-University of Jena
  • Prof. Marom Bikson, Department of Biomedical Engineering, The City College of New York, NY, USA
  • PD Dr. rer. nat. Jürgen Fell, AG Fell - Cortical oscillations, Universitätsklinikum Bonn
  • Dr. rer. nat. Leila Chaieb, AG Fell – Cortical oscillations, Universitätsklinikum Bonn
  • Prof. María Teresa Carrillo de la Peña, Department of Clinical Psychology and Psychobiology, Universidad de Santiago de Compostela, Spain

Leading researcher

Leitung

Prof. Dr. Andrea Antal

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Team

Studentische Hilfskraft

Clara Brakebusch

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Postdoc

Dr. Ivan Chakalov

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MSc, PhD Student

Lukas Diedrich

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BA, MSc student

Rebecca Divarco

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