Smart Brain-Zapping Implants Could Revolutionize Parkinson’s Treatment
New deep-brain-stimulation implants for Parkinson’s disease can listen in on brain waves and adapt to treat symptoms. Can this approach target other conditions?
Keith Krehbiel lived with Parkinson’s disease for nearly 25 years before agreeing to try a brain implant that might alleviate his symptoms. He had long been reluctant to submit to the surgery. “It was a big move,” he says. But by 2020, his symptoms had become so severe that he grudgingly agreed to go ahead.
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Since DBS was first approved in Europe and the United States in the late-1990s, the vast majority of devices have been given to people with Parkinson’s disease. Parkinson’s is a progressive disorder, typified by the death of neurons that produce the neurotransmitter dopamine, which is key to controlling movements.
Existing drugs that aim to increase dopamine levels can only manage the symptoms. They can’t match the constant dopamine production of a healthy brain. “No matter how clever we are with it, we have never been able to exactly mimic the way the brain supplies it,” says Bronte-Stewart. This means that symptoms vary throughout the day — from the unwanted involuntary movements induced by the morning flood of dopamine-mimicking drugs to increased rigidity later in the day as the drugs wear off. The medication also comes with other side effects that vary from person to person. For Krehbiel, it was nausea so severe he had to lie down multiple times a day.
But continuous DBS can sometimes amplify the drugs’ effects — or generate new symptoms. Some of these are harmless: one man with OCD developed a passion for the music of Johnny Cash when his stimulator was turned on, but was uninterested in the artist when it was off. Other symptoms are cause for more concern, including sudden-onset gambling disorders and other temporary changes in impulse control. More frequently, the addition of stimulation can induce speech impairments, such as slurring, raise the risk of falling and cause some involuntary movements.
A clinician can try to balance the system by adjusting the intensity of stimulation, but there are limits to how precisely it can be calibrated.
Brain-wave activity is different in people with and without Parkinson’s disease. In people with Parkinson’s, there are noticeable differences at one range of frequencies, known as β-oscillations (between about 13 and 30 hertz), in a region deep in the brain called the basal ganglia. This region processes sensorimotor, cognitive and mood information.
β-oscillations have become an important marker of motor state. In the early 2000s, researchers at University College London found increasing evidence that people with Parkinson’s have intense bursts of activity in this range. When drug treatments are working, these bursts are less exaggerated. The same is true for DBS. The more that stimulation normalizes β-oscillations, the better the relief of some symptoms, says Bronte-Stewart.
Aberrant oscillations were dubbed oscillopathies, and in the 2000s, Medtronic started focusing on developing a device that could both read and correct these rhythms, says Tim Denison, a biomedical engineer at the University of Oxford, UK, who was working at the company at the time. “Just like you can build a radio to tune in to an audio channel, can we build a circuit that will tune in to these oscillopathies and help to guide how to adjust the stimulator?” he asks.
By 2006, Denison and his colleagues had built a ‘brain radio’, a sensing chip that could tune in to the different frequency bands in which the electrode sits. The next challenge was finding out how changes in particular bands correspond to specific movement problems. That was “a huge part of the first eight to ten years of the research with the investigational hardware”, says Bronte-Stewart. She and other researchers, including Philip Starr at the University of California, San Francisco, used a succession of new prototype devices to map these oscillopathies and adjust to them.
For example, when β-oscillation intensity begins to dip after a dose of medication, aDBS automatically reduces stimulation, keeping β-power in a healthy range. As the medication wears off, it does the opposite (see ‘Fine-tuned stimulation’). In 2019, Bronte-Stewart developed one of the algorithms that would underpin aDBS. When she tested it on 13 people with Parkinson’s, it improved the halting movements, called bradykinesia, that are associated with the disease. It also helped to reduce the inability to take steps, known as freezing of gait, in a study last year. In a separate study, Starr found that aDBS shortened the duration of volunteers’ most bothersome motor disturbances, but without aggravating side effects.
Any Medtronic DBS implant manufactured after 2020 has the ability to be switched into adaptive stimulation mode. If people were enrolled in a clinical trial after 2020, their implant’s experimental capabilities could be activated by a firmware update, “a software unlock, like your iPhone”, says Raike. This approach opened up a large pool of possible trial participants. And the capability could be turned back off at the end of the trial.
After two months with continuous DBS, Bronte-Stewart unlocked Krehbiel’s device. It continued to keep his tremor at bay. He needed fewer drugs.
Other trial volunteers have reported similar improvements, along with a reduction of symptoms associated with continuous stimulation. Although she is not permitted to discuss the results, which are still pending publication, Bronte-Stewart points to data presented at a 2024 conference. Of 45 volunteers in the trial who were given the choice to revert to the continuous DBS or to retain the new adaptive functionality for a further long-term follow-up, 44 chose to stay on aDBS, Krehbiel among them. “I would not have considered for more than 30 seconds reverting back,” he says. “I was feeling good and didn’t much care why.”
Beudel saw a broadly similar trend among his participants. “It’s no secret that the results were positive,” he says. “We now see patients from all over the country coming to our centre saying that they want the aDBS.”
Since the new system was approved earlier this year, the upgrade has been available to anyone with one of the post-2020 devices. Beyond straightforward symptom relief, these users might see beneficial effects that go beyond controlling motor symptoms.
For example, Parkinson’s disease notoriously interferes with sleep, and as the medicine wears off at night, problems emerge that range from insomnia to hallucinations. Sleep deprivation, in turn, worsens the symptoms. “It is a vicious circle,” says Beudel.
Adaptive DBS could reduce sleep disturbances by automatically adjusting to the sleep-induced changes in β-oscillations.
And better sleep might, in turn, protect the brain. If it does, says Denison, aDBS could shed light on the tantalizing but controversial hypothesis that DBS protects the brain when implanted earlier in Parkinson’s disease progression.
It’s not just people with Parkinson’s who might benefit from the new therapy. Slightly more than one-quarter of the estimated 230,000 people with a DBS implant use it to manage other diseases, including dystonia — a movement disorder that causes muscles to contract — essential tremor and OCD.
Researchers are working to identify the associated oscillopathies to allow them to extend aDBS to these populations, and to those whose conditions have not yet been approved for any form of DBS, including Tourette’s syndrome. Beudel is exploring oscillopathies that precede the onset of tremor. Michael Okun, a neuroscientist at the University of Florida in Gainesville, has identified oscillations that could be quashed to dial down tics in Tourette’s syndrome.
Adaptive DBS has also raised hopes for treatment-resistant depression, which would represent a much larger market than Parkinson’s disease. Although DBS is not approved for this condition anywhere in the world, a few hundred people have had experimental implants.
But Mayberg might be zeroing in on a signal that is associated with individuals getting better: this brain-oscillation pattern emerges as symptoms recede. A month after the brain signal disappeared in one participant with depression, they relapsed.
This work is in its early days, but Mayberg thinks the sensing capabilities of modern devices might one day provide a ‘check engine’ warning light for possible relapse.
As Medtronic and other companies continue to enhance their DBS systems, the number of electrodes and their sophistication has risen swiftly. Some researchers, including Denison and Bronte-Stewart, say that the line is blurring between DBS and brain–computer interfaces.
The enhanced sophistication puts pressure on the clinicians in charge of managing the complex device settings. “Who is going to program these?” asks Okun. He worries that the proliferation of smarter devices could make them, paradoxically, less accessible to people owing to the already-huge demands on clinicians’ time.
All the while, the number of people with Parkinson’s is expected to nearly double globally by 2050: to 25 million.
To meet that need, the goal is to make the process as accessible as it was for Krehbiel. “I had the opportunity to get the secret sauce,” he says, “so why not go for it?”
This article is reproduced with permission and was first published on July 15, 2025.
Sally Adee is a science journalist in London.
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Source: www.scientificamerican.com