Researchers Uncover Link Between Dopamine and DBS in PD

by James Cavuoto, editor

October 2024 issue

One of the greatest challenges confronting neural engineers developing new therapies for neurological disorders is understanding the mechanisms underlying normal and dysfunctional activity. This is particularly true when neuromodulation therapies arise to treat disorders where pharmacological approaches have fallen short.

Parkinson’s disease represents a prime example of this situation. Neurologists recognize that the lack of the neurotransmitter dopamine is a critical factor in the onset of the disease, yet efforts to replace natural dopamine with drugs such as L-dopa have limited success, with diminished effectiveness over time and considerable side effects. Deep brain stimulation has emerged as a second-line approach that produces improved results in patients after pharmaceuticals have lost effectiveness. But despite some clinicians’ efforts to position DBS as potentially curative and accelerate its deployment in the progression of the disease, pharmaceutical regimens remain as the first line therapy and the penetration of DBS systems in the movement disorders market remains in the low single digits.

Recently, a team of researchers from Germany and China has uncovered significant findings concerning the role that both dopamine and neuromodulation play in reversing the effect of Parkinson’s disease. These findings promise to enhance the effectiveness of both neuromodulation and pharmacological approaches to treating movement disorders.

Researchers from Charité–Universitätsmedizin Berlin showed that DBS can actually mimic the effects of dopamine. Reporting in the journal Brain, they described how dopamine influences networks inside the brain that transmit the intentions that precede voluntary movement. The goal is to unlock further advances in DBS.

Slow movement, tremor, and stiff muscles are all typical symptoms of Parkinson’s disease. Neuroscientists Andrea Kühn, John-Dylan Haynes, and Wolf-Julian Neumann at Charité and their colleagues from Beijing Tiantan Hospital sought to discover what happens inside the brain in the seconds before a person lifts their arm or clenches their fist. They wanted to know where dopamine fits in the communications taking place in the circuits of the brain responsible for these movements.

One of the key symptoms of PD is loss of the ability to initiate movements voluntarily, a symptom known as akinesia. Affected patients move more slowly. “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,” explained 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.”

“We harnessed a combination of really unusual methods,” Kühn explained. “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 said.

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 DBS. Communication in the brain’s network was accelerated, and the delay in movement that is typical of Parkinson’s disease was shortened,” Neumann said.

“This is especially exciting because in the future, we could use DBS as a kind of intelligent brain-computer interface,” he noted, 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.