German Clinical Trials Register

Acronym/abbreviation of the study

TETRIS

URL of the study

No Entry

Brief summary in lay language

This study investigates the mechanisms and the effect on movement disorders and emotional symptoms of non-invasive brain stimulation in Parkinson's disease patients and healthy individuals. In Parkinson's disease, there is a lack of neurotransmitters in certain regions of the brain, which leads to a malfunction of the nerve cells, which in turn leads to an altered electrical signal transmission between the nerve cells. This results in the classic symptoms of the disease. On the one hand, there may be a disturbance in movement processes, e.g. tremor or stiffness. On the other hand, neuropsychological symptoms can also occur, such as dejection, lack of concentration or apathy. A number of treatment options have been established, the two mainstays of which are medication and brain stimulation. Currently, it is necessary to surgically implant the electrodes for brain stimulation directly in the corresponding brain regions. Accordingly, despite its good efficacy, the therapy is fraught with possible severe side effects. A newly developed approach, the so-called "transcranial temporal interference stimulation" (tTIS), makes it possible to stimulate regions deep in the brain without the need for surgery. The electrodes for the stimulation are temporarily attached to the scalp. The underlying mechanisms have not yet been researched in detail. In order to better understand the processes and the effects, we would like to perform a stimulation by means of tTIS on different groups of persons, while different tasks (an explanation can be found in the next section) are set. We would like to investigate a) how stimulation affects Parkinson's disease patients and healthy subjects in comparison, b) what effects stimulation has on movement patterns, and c) how motivation changes as a result of stimulation. In addition, we are investigating techniques to simulate this method.

Brief summary in scientific language

Transcranial temporal interference stimulation (tTIS) is a new method to non-invasively stimulate regions in the depth of the brain. The idea behind this is to send out two very-high frequencies that do not interfere with brain activity, which are slightly different (e.g. 2 kHz and 2,1 kHz) and are overlapping in the region of interest (ROI) in deep brain regions such as the basal ganglia. In this way, the frequencies extinct each other with only the delta of both frequencies (in this example 0,1 kHz) targeting in the ROI. This frequency then stimulates the deep laying regions. Overlying cortical layers are not affected by this technique. The current is applied by electrodes which are placed on the scalp of the participants. Previous studies demonstrated the efficiency of tTIS in an animal model and the safety of tTIS in humans. The studies of this application extent the research question to a proof of principle of tTIS in a disease model namely Parkinson’s disease (PD). In this project, tTIS will be applied for the first time in PD patients. One major symptom complex are the motor symptoms, which are caused by neuronal oscillation changes in the basal ganglia, namely the putamen. Another aspect of this disease are non-motor symptoms like apathy, which is defined by a lack of motivation. This is thought to be caused by changed oscillations in the region of the nucleus accumbens. To provide an exact stimulation, we will simulate the stimulation on a single-subject level with individual MRI scans. In the second phase, the two different aspects of this disease are investigated. First, we stimulate the putamen of the participants. The change in motor performance will be measured with a finger tapping task, which is analyzed by a 3D video camera system. Another sequential finger tapping task is performed to measure motor learning. Second, the nucleus accumbens will be stimulated with a gamma frequency to enhance effort-reward behavior and therefore modulate the motivation. This is tested with a well-established motivation task, in which the participants have to squeeze a hand grip to gain rewards. The studies will be accompanied by a standardized safety investigation. Using a cross-over real or sham design, the impact of tTIS on motor and non-motor symptoms will be investigated in order to perform feasibility, safety and a first prove of concept of tTIS to treat motor and non-motor aspects of a neurodegenerative disease.