Keith Krehbiel battled Parkinson’s disease for nearly 25 years before he decided to undergo a procedure to implant a device in his brain, hoping it would ease his worsening symptoms. Despite his initial hesitation about the surgery, by 2020, the severity of his symptoms left him with little choice but to proceed.
Deep-brain stimulation (DBS) is a technique that involves placing thin electrodes through small openings in the skull to reach areas of the brain that influence movement. The goal is to deliver electrical pulses to these areas to help normalize irregular brain activity and lessen symptoms. Since the initial approval of these devices nearly three decades ago, around 200,000 individuals have received them to manage the shaking and stiffness associated with Parkinson’s disease. However, about 40,000 of these devices implanted after 2020 came with a new, mostly inactive feature. These devices have the capability to monitor brain activity and adjust the stimulation pattern accordingly, similar to how a pacemaker adjusts to heart rhythms, explains Helen Bronte-Stewart, a neurologist at Stanford University.
Around the time Krehbiel was preparing for his surgery, Bronte-Stewart received the green light to begin a clinical trial with this new technology, known as adaptive deep-brain stimulation (aDBS). Excited about the prospect, Krehbiel eagerly agreed to be the first participant.
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Five years later, the results of the 68-person ADAPT-PD trial are being reviewed for publication. While specifics remain confidential, the findings were compelling enough to receive approval from regulatory authorities in both the United States and Europe earlier this year.
The study’s outcomes could significantly benefit the estimated one million people in the U.S. and 1.2 million in Europe living with Parkinson’s disease. It could also prove advantageous for Medtronic, the Minneapolis-based company that manufactures these implants. The positive results also pave the way for other companies globally to seek approval for advanced devices, notes Martijn Beudel, a neurologist involved in the trial from the Amsterdam University Medical Center.
The emerging therapies are set to enhance DBS for Parkinson’s and other motor disorders. The technology might also aid in treating neurological conditions like Tourette’s syndrome and psychiatric disorders such as obsessive-compulsive disorder (OCD) and depression. Many clinicians believe the new technology could have broader health implications, especially if funding for brain implant research in the U.S. remains intact.
Deep Trade-offs
Since their approval in the late 1990s in Europe and the U.S., DBS devices have primarily been used to treat Parkinson’s disease, a progressive disorder marked by the death of dopamine-producing neurons essential for movement control.
Existing drugs that boost dopamine levels only manage symptoms and can’t replicate the consistent dopamine output of a healthy brain. “We’ve never been able to perfectly mimic the natural supply of the brain,” Bronte-Stewart admits. This results in symptom fluctuations throughout the day, from involuntary movements caused by morning doses of dopamine-like drugs to increased stiffness as the medication wears off. Krehbiel, for instance, experienced severe nausea as a side effect, forcing him to lie down frequently.
When symptoms become unbearable, neurologists may recommend DBS. Traditionally, implants have delivered continuous electrical pulses to control erratic brain signals linked to uncontrollable movements. However, continuous DBS can sometimes exacerbate the effects of drugs or introduce new symptoms, such as speech impairments or increased risk of falls. Adjusting the intensity of stimulation offers some relief, but the calibration’s precision is limited.
Recognizing these limitations, Krehbiel waited for newer technology before opting for DBS as a last resort.
Catching Waves
Differences in brain-wave activity between individuals with and without Parkinson’s are pronounced in a frequency range known as β-oscillations (13 to 30 hertz) within the basal ganglia, a deep brain region involved in processing sensorimotor, cognitive, and mood-related information.
These oscillations serve as a crucial indicator of motor state. Early research from University College London in the 2000s showed that intense bursts of β-oscillations are common in Parkinson’s patients, and both medication and DBS can moderate these bursts. “The more effectively stimulation normalizes β-oscillations, the better the symptom relief,” says Bronte-Stewart.
In the mid-2000s, Medtronic focused on developing a device capable of both monitoring and adjusting these rhythms. “Can we build a circuit that tunes into these oscillopathies and helps guide stimulator adjustments?” posed Tim Denison, a biomedical engineer at the University of Oxford, who was with Medtronic at the time.
By 2006, Denison and his team had created a ‘brain radio’, a sensing chip that could detect different frequency bands where the electrode resides. Identifying how changes in specific bands correlate with particular movement issues was a significant focus of the early research with investigational hardware. Bronte-Stewart and other researchers, including Philip Starr from the University of California, San Francisco, used new prototype devices to map these oscillopathies and adjust to them.
For instance, when β-oscillation intensity decreases after a dose of medication, aDBS automatically lowers stimulation, maintaining β-power within a healthy range. Conversely, as the medication wanes, the stimulation increases. In 2019, Bronte-Stewart developed an algorithm foundational to aDBS, which, when tested on 13 Parkinson’s patients, improved symptoms like bradykinesia (slowed movement) and freezing of gait. Starr’s separate study found that aDBS reduced the duration of volunteers’ most troubling motor disturbances without worsening side effects.
Other research indicates that aDBS may also mitigate speech issues, such as slurring, another potential side effect of continuous DBS. “It only suppressed the pathological brain activity,” notes Beudel, without affecting normal speech functions.
Since 2013, small trials have demonstrated these effects in approximately 400 individuals, according to Robert Raike, director of neuromodulation research and technology at Medtronic. However, validating these findings in real-world settings—people’s homes and workplaces over extended periods—required a larger trial.
A Personalized Device
Any Medtronic DBS implant made after 2020 can switch to adaptive stimulation mode. For those enrolled in clinical trials post-2020, their implant’s experimental features could be activated through a firmware update, “similar to a software unlock on your iPhone,” explains Raike. This feature could be deactivated at the trial’s conclusion.
Two months after receiving continuous DBS, Bronte-Stewart activated the adaptive feature on Krehbiel’s device, which continued to control his tremors effectively while reducing his medication needs.
Other trial participants reported similar improvements and a decrease in symptoms associated with continuous stimulation. Though she cannot discuss the still-pending results, Bronte-Stewart references data presented at a 2024 conference. Of 45 volunteers given the option to revert to continuous DBS or keep the new adaptive functionality for further long-term follow-up, 44 chose to continue with aDBS, including Krehbiel. “I wouldn’t have considered reverting for more than 30 seconds,” he remarks. “I was feeling good and wasn’t concerned about why.”
Beudel observed a similar trend among his participants. “It’s no secret that the results were positive,” he says. “We now see patients from across the country visiting our center, requesting aDBS.”
Since the system’s approval earlier this year, the upgrade has been available to anyone with a post-2020 device. Beyond simply managing motor symptoms, these users might experience benefits that extend to controlling other aspects of Parkinson’s disease.
For example, the disease often disrupts sleep, leading to issues ranging from insomnia to hallucinations as the medication wears off at night. Sleep deprivation, in turn, exacerbates symptoms, creating a “vicious circle,” according to Beudel. Adaptive DBS could alleviate sleep disturbances by automatically adjusting to the sleep-induced changes in β-oscillations.
Improved sleep might also protect the brain. If true, says Denison, aDBS could support the intriguing yet controversial hypothesis that earlier DBS implantation in Parkinson’s disease progression could offer neuroprotective benefits.
Beyond Parkinson’s
The potential of the new therapy extends beyond Parkinson’s disease. Approximately one-quarter of the estimated 230,000 individuals with a DBS implant use it to manage other conditions, including dystonia—a movement disorder causing muscle contractions—essential tremor, and OCD.
Researchers are identifying the oscillopathies associated with these conditions to potentially extend aDBS to these groups and others not yet approved for any DBS treatment, such as Tourette’s syndrome. Beudel is investigating oscillopathies that precede tremor onset, while Michael Okun, a neuroscientist at the University of Florida in Gainesville, has identified oscillations that could be targeted to reduce tics in Tourette’s syndrome.
Although evidence for psychiatric conditions is less robust, Starr notes, “they might have oscillopathies that could be DBS targets.” OCD shows particular promise, according to Damiaan Denys, a psychiatrist at the University of Amsterdam. In an upcoming study, his team found clear associations between compulsions and specific brain signatures. “We are close to identifying some of these neurological imprints,” he says.
Adaptive DBS also raises hopes for treating treatment-resistant depression, potentially a much larger market than Parkinson’s disease. Although DBS is not approved for depression anywhere globally, a few hundred people have received experimental implants.
Helen Mayberg, a neurologist at Icahn School of Medicine at Mount Sinai in New York City, led two of the largest depression trials to date, both of which failed to meet their primary endpoints. Mayberg obtained one of Medtronic’s early prototype brain radios to explore the potential role of oscillations in depression. Like Parkinson’s, depression has many symptoms, but no specific abnormal oscillations have been linked to it. “If you gather ten people with depression,” says Alik Widge, a psychiatrist and biomedical engineer at the University of Minnesota, “you wouldn’t see the same oscillopathy.”
However, Mayberg might be closing in on a signal associated with improvement: this brain-oscillation pattern emerges as symptoms recede. In one case, a participant with depression relapsed a month after this brain signal disappeared.
This research is still in its early stages, but Mayberg believes the sensing capabilities of modern devices could eventually provide a ‘check engine’ warning light for potential relapse.
Overcomplicating the Problem?
As Medtronic and other companies continue to enhance their DBS systems, the complexity and number of electrodes have increased rapidly. Some researchers, including Denison and Bronte-Stewart, suggest that the distinction between DBS and brain–computer interfaces is becoming blurred.
The growing sophistication places additional pressure on clinicians responsible for managing the intricate device settings. “Who will program these?” questions Okun. He is concerned that the proliferation of smarter devices could paradoxically make them less accessible due to the already significant demands on clinicians’ time.
Medtronic is developing more automated programming technologies to save time: one new technology, approved this year, simplifies the programming process. Artificial intelligence could further refine settings; the U.S. Food and Drug Administration is developing new standards for automation. However, further advances will require more extensive studies, like ADAPT-PD and the smaller studies that preceded it. These studies are expensive. “Each patient can cost a million bucks or more,” says Okun. But the future of a major funding source for DBS is uncertain. Even before the new U.S. administration began cutting funds for medical research, Congress slashed the BRAIN Initiative— the U.S. National Institutes of Health’s neurotechnology innovation accelerator—by 40% last year. “We’re all concerned about where the funding will come from to develop these types of studies,” Bronte-Stewart admits, although other countries are picking up the slack.
Meanwhile, the global population of people with Parkinson’s is expected to nearly double by 2050, reaching 25 million.
To meet this growing 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.
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