Tissue-friendly electrodes, developed by researchers at Lund University in Sweden, are now undergoing clinical trials at Skåne University Hospital. Using 30 electrodes, each thinner than a strand of hair, the researchers aim to investigate the possibility of more precise stimulation and mapping of the brain prior to deep brain stimulation (DBS).
Our movement patterns, among other things, are controlled from deep within our brain in areas known as the thalamus and subthalamus. In Parkinson's disease, where a lack of dopamine disrupts communication between different parts of the brain, deep brain stimulation (DBS) in this area can help the neural circuits to regain a more normal function. This can help to reduce tremors and enable the patient to regain some of the control that the condition has taken away from it.
However, there are many challenges associated with current treatment. Just a fraction of a millimetre can determine whether the stimulation relieves the symptoms or causes side effects instead. Furthermore, the anatomy of the brain varies from person to person, which means that the electrodes are not always positioned optimally.
"Another challenge has been that electrodes inserted into brain tissue often cause localised loss of nerve cells and inflammation, which can lead to scar tissue, that may in turn reduce the effectiveness of DBS. It's these problems that we now want to tackle," says Jens Schouenborg, the professor who leads research activities at the Neuronano Research Center at Lund University.
The electrode technology developed by the research team, High Definition Brain Stimulation (HDBS), will be investigated in patients with Parkinson's disease or essential tremor - a condition that causes involuntary tremors. HDBS, which consists of very small, soft, seaweed-like microfibres that are highly biocompatible and designed to function effectively in contact with the body's tissues, can interact with brain tissue in a different way to current technology.
"As we now can use very weak electrical signals, the stimulation is gentle. The signals are on a par with those used by the nerve cells themselves, and at the same time we can avoid areas where stimulation of the nerve cells risks causing side effects."
Twelve patients are taking part in the study, which is being conducted at Skåne University Hospital under the supervision of neurosurgeon Hjalmar Bjartmarz.
"The electrodes we use today in DBS treatment are essentially the same as those developed 30 years ago. If this study shows that the new, thinner nanoelectrodes are able to stimulate the brain and produce an effect, this will be a major breakthrough that could, in the long term, revolutionise the field," says Hjalmar Bjartmarz.
The aim of the study is to investigate whether the new technology can produce powerful therapeutic effects with minimal side effects, as has previously been achieved in animal experiments.
"At the same time, we are mapping the brain's response to stimulation so that we can position the DBS electrodes more precisely," says Hjalmar Bjartmarz.
The microelectrodes are connected to a battery-powered stimulator, and the researchers can then stimulate small, defined areas of nerve cells. The microelectrodes form clusters in the target area and, with the help of feedback from the patient, the staff are able to determine how the stimulation in different parts of the cluster is perceived and how it affects tremors and movements. The information is also used to create a three-dimensional map that can help the neurosurgeon determine the optimal placement of the planned permanent DBS electrode.
"The electrodes are very soft, so in order to position them exactly where we need them in the brain, we need something to guide them. That is why, among other things, we have developed a system of tiny microchannels in gelatine that helps us guide the electrodes correctly. The gelatine then dissolves," says Jens Schouenborg.
Ever since Jens Schouenborg and his colleagues at the Neuronano Research Center began their research into brain electrodes in 2006, the vision has been both to facilitate advanced brain research into how nerve cells communicate with one another under normal conditions - and to develop new and effective treatments for degenerative diseases.
The researchers initially focused on making the electrodes and the methods for inserting them into the brain as gentle as possible on the tissue. Once they had succeeded in minimising the impact on brain tissue, they began to develop the technique for use in treatment. The medical technology company Neuronano AB has also been involved in this technological development. Its role includes ensuring that the experimental device meets regulatory requirements.
"Following promising results in animal trials and extensive pre-clinical safety testing, the technology is now to be evaluated in patients. Many years of hard work have gone into this project, so it feels really good to now be able to take this step towards better treatment for Parkinson's disease and essential tremor," says Jens Schouenborg.
The technique has proved effective in animal trials focusing on both pain and Parkinson's disease.
"We therefore hope that, in the long term, this electrode technology will also be able to be used for many other chronic conditions for which there is no effective treatment - such as Alzheimer's disease and other forms of dementia, treatment-resistant high blood pressure, insomnia and so on," says Jens Schouenborg.
Parkinson's disease
Parkinson's disease is a neurological disorder in which nerve cells in an area deep within the brain are gradually lost. The cells produce dopamine - a neurotransmitter that plays a crucial role in the brain's control of the body's movements. When dopamine levels fall, communication between different parts of the brain deteriorates, making it more difficult to control the muscles.
The most common symptoms are:
- Tremors, particularly when the body is at rest
- Muscle stiffness and increased muscle tension
- Slow and sluggish movements, which can be difficult to initiate
Source: Swedish Brain Foundation
