Parkinson’s disease: Brain stimulation can mimic effects of dopamine

Slow movement, tremor, and stiff muscles are all typical symptoms of Parkinson’s disease. They are due to loss of the neurotransmitter dopamine, known as the “feel-good” hormone. Treatment for Parkinson’s disease involves medications to replace dopamine, often with side effects. Researchers from Charité – Universitätsmedizin Berlin have now shown that deep brain stimulation (DBS) using electrical impulses can mimic the effects of dopamine. In an article in the journal Brain,* they describe how dopamine influences networks inside the brain that transmit the intentions that precede voluntary movement. The goal is to unlock further advances in DBS.

What happens inside the brain in the seconds before a person lifts their arm or clenches their fist? Where does the neurotransmitter dopamine fit into the communications taking place in the circuits of the brain responsible for these movements? And might targeted stimulation of specific areas of the brain simulate the effects of dopamine? Those were the questions for a team of researchers led by neuroscientists Prof. Andrea Kühn, Prof. John-Dylan Haynes, and Prof. Wolf-Julian Neumann at Charité.

The project was spearheaded by early-career scientist Richard Köhler and together with international colleagues of the ReTune collaborative research center, which is working to advance the treatment of patients with movement disorders through deep brain stimulation (DBS). In this method, electrodes are implanted into the brain, that transmit electrical impulses to the nerve cells that are affected by Parkinson’s disease.

One of the key symptoms of this neurological disorder, is loss of the ability to initiate movements voluntarily, a symptom known as akinesia. This means affected patients move more slowly. The root cause of the disorder is a deficiency of dopamine, an important neurotransmitter responsible for transmitting information in the brain. “The dopamine system is essential to human behavior, governing not only how we feel and experience emotions and the reward response but also how we plan and execute movements,” explains Neumann, who led the study. “How this neurotransmitter affects the intention that triggers movement and to what extent DBS can simulate this effect were previously unknown.” The researchers set out to close this crucial gap in scientists’ knowledge and pave the way for new therapeutic approaches.

Machine learning helps “read people’s minds”

Parkinson’s disease is undergoing the fastest growth in prevalence among neurological disorders worldwide. Those with the disease experience significantly worsened quality of life. There is no cure. Treatment typically involves taking medications to replace the natural dopamine that is lacking in the body. However, the medications become less effective over several years, and serious side effects occur. DBS becomes an option for some patients in this situation. To make the procedure more effective and more accurate, the neuroscientists went to the root of where movements originate, studying how the brain prepares for those movements.

“We harnessed a combination of really unusual methods,” Kühn explains. “We measured the signals in areas of the cerebral cortex that trigger movement and deep inside the brains of Parkinson’s disease patients who had undergone neurosurgery for DBS while they performed deliberate movements. Then we read those brain signals using a brain-computer interface and methods drawn from the field of machine learning.” This allowed the researchers to trace the intentions that precede movement to very early on in the process, even before the muscles themselves are activated. The team is extremely grateful to the 25 patients who took part in the study, which would have been impossible if not for their participation.

The scientists were able to decode the intent preceding voluntary movement seconds before the action itself occurred. To pinpoint the effects of dopamine, they repeated the process before and after a dose of the substance was given to the test subjects. The results were astonishing: “Dopamine significantly accelerates the process that takes place between the initial intention, meaning the point when the brain shows the first signs that movement is being planned, and the time when the movement actually occurs. The frequency of the brain signals changes as well, leading to faster execution of a movement,” Haynes says.

Basis for intelligent “brain pacemakers”

The loss of dopamine in Parkinson’s disease affects the communication between deep regions of the brain and the motor cortex, so the frequency of communications shifts. This is exactly where the team’s therapeutic approach comes in: “We were able to imitate the effects of dopamine through targeted deep brain stimulation. Communication in the brain’s network was accelerated, and the delay in movement that is typical of Parkinson’s disease was shortened,” Neumann says.

“This is especially exciting because in the future, we could use deep brain stimulation as a kind of intelligent brain-computer interface,” he notes, looking to developments on the horizon. “Once the intention to carry out a movement is recorded, electrical impulses could be used to accelerate the process between that step and actually executing the movement.” These kinds of prosthetic aids to signaling in the brain can correct disordered signaling patterns – in this case, decoding the intent to move in real time and triggering brain stimulation as soon as it arises in the patient. Further research will follow with the aim of advancing this form of treatment.

*Köhler RM et al. Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease. Brain 2024 Oct 3. doi: 10.1093/brain/awae219.

About the study
The study is a key component of collaborative research center TRR295, ReTune, which is receiving funding from the German Research Foundation (DFG). Wolf-Julian Neumann and Stefan Haufe also received support from the European Research Council (ERC). Andrea Kühn received a grant from the Lundbeck Foundation, and the NeuroCure Clinical Research Center also contributed to the implementation of the project.