Bernstein members involved: John-Dylan Haynes, Wolf-Julian Neumann

What happens in the brain in the seconds before an arm lifts or a hand closes? What role does the neurotransmitter dopamine play in the communication between the responsible brain circuits? And could the effect of dopamine possibly be recreated by stimulating specific areas of the brain? These questions were asked by a research team led by neuroscientists Prof. Andrea Kühn, Prof. John-Dylan Haynes and Prof. Wolf-Julian Neumann at Charité.

In the ReTune Collaborative Research Center, led by junior scientist Richard Köhler and together with international colleagues, the team is working on advancing the treatment of patients with movement disorders using deep brain stimulation. This involves inserting fine electrodes into the brain. They send electrical impulses to nerve cells that influence certain movements. The neurosurgical procedures required for this are carried out at Charité and elsewhere.

A key symptom of Parkinson’s disease is the loss of the ability to trigger movements voluntarily. Sufferers therefore only perform movements slowly. This is known as akinesia. The disorder is caused by a deficiency of the neurotransmitter dopamine. Its task is to transmit information in the brain. “The dopamine system is essential for human behavior, for emotional perceptions or responding to rewards, but also for planning and executing movements,” explains study leader Wolf-Julian Neumann. “How the neurotransmitter influences the intention to initiate a movement and to what extent deep brain stimulation can mimic this effect was previously unknown.” The researchers wanted to close this crucial knowledge gap and pave the way for new therapeutic procedures.

Machine learning helps with “mind reading”

Parkinson’s is the fastest growing brain disease worldwide. Those affected are significantly restricted in their quality of life and there is no cure. Treatment is usually with medication that replaces the missing dopamine. After a few years, however, the effect wears off and severely debilitating side effects set in. For some patients in this situation, deep brain stimulation is an option. To make the procedure even more effective and precise, neuroscientists have started at the point where movements occur and investigated how they are prepared in the brain.

“We made use of a combination of quite unusual methods,” explains Andrea Kühn. “In Parkinson’s patients who had undergone neurosurgery for deep brain stimulation, we measured brain signals from movement-inducing areas of the cortex and from deep in the brain while they were performing conscious movements. We then read out these brain signals using a brain-computer interface and machine learning methods.” This made it possible to detect an intention to move at a very early stage, even before the actual muscle activation. Such a study would not have been possible without the commitment of the 25 patients. The research team would therefore like to expressly thank them.

The researchers were able to decode the intention to move seconds before the actual action. In order to track down the influence of dopamine, they repeated the process before and after administering the neurotransmitter – with astonishing results: “Dopamine significantly accelerates the process from the intention to move, i.e. the time at which the brain first indicates that a movement is being planned, to the actual execution. The frequency of the brain signals also changes, which leads to a faster implementation of a movement,” says brain researcher John-Dylan Haynes.

Basis for intelligent brain pacemakers

The loss of dopamine in Parkinson’s syndrome impairs communication between deep brain regions and the motor cortex, and the communication frequency also shifts. This is precisely where the team’s therapeutic approach comes in: “Through targeted deep brain stimulation, we were able to mimic the effect of dopamine. Communication in the brain network became faster and the movement delay typical of Parkinson’s shortened,” says Wolf-Julian Neumann.

“This is particularly exciting because we could use deep brain stimulation as an intelligent brain-computer interface in the future,” says the neuroscientist, looking ahead. “As soon as the will to make a movement is read out, the path to its execution could be accelerated by means of electrical impulses.” Such so-called brain circuit prostheses can correct pathologically altered brain signal patterns – in this case decoding movement intentions in real time and triggering brain stimulation as soon as patients want to move. Further research will follow in order to further develop this form of therapy.