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In the study, published Monday in the journal Nature Medicine, researchers turned deep brain stimulation, an established treatment for Parkinson’s, into a personalized therapy that adjusts the amount of electrical stimulation based on each patient’s individual symptoms.
For Connolly and three other participants, the personalized treatment, called adaptive deep brain stimulation, cut in half the time they spent experiencing their most bothersome symptoms, the researchers found.
Connolly, 48, who still skates as much as his condition allows, said he noticed a difference “right away.” He said the personalized treatment has allowed him to “feel good and have more energy” for longer.
The study also found that in most cases, patients’ quality of life improved. “That’s very important,” said Dr. Samir Sheth, a professor of neurosurgery at Baylor College of Medicine who was not involved in the study.
While the study was small, it represents progress toward using brain implants and artificial intelligence to personalize treatments for neurological and psychiatric disorders—essentially developing a pacemaker for the brain.
Recent experiments have begun to personalize brain stimulation for depression, obsessive-compulsive disorder, and chronic pain. Although more research is needed, as well as how to make these approaches practical and affordable, some experts predict that some version of a brain pacemaker could be available within five or ten years.
“I do think this suggests that personalized, individualized stimulation is really the wave of the future,” said Dr. Jamie Henderson, a professor of neurosurgery at Stanford University who was not involved in the study.
Deep brain stimulation has been used for years to treat Parkinson’s disease. The therapy is usually started after patients have achieved maximum benefit from medications containing levodopa, a drug that combats a deficiency of the hormone dopamine that causes Parkinson’s disease.
With traditional deep brain stimulation, patients receive a constant level of electrical pulses. While this approach helps most patients, many eventually reach a plateau, or because the treatment cannot be adjusted to the patient’s experience, the stimulation may be too much or too little, causing the patient to fluctuate wildly between rigidity and uncontrolled movements.
“This does not mean that we have maximized, optimized or determined our ability to treat people with Parkinson’s disease,” Sheth said.
In recent years, neuroscientists have identified brain signals that correspond to phases of rigidity, called bradykinesia, and phases of uncontrolled movement, called dyskinesia. In the new study, the researchers used methods derived from artificial intelligence to design a personalized algorithm for each patient and a way to detect and respond to brain activity as patients’ symptoms fluctuate.
“The brain’s needs change moment to moment, hour to hour, week to week,” said Dr. Philip Stahl, a UCSF professor of neurosurgery and senior author of the study, who has been working on deep brain stimulation for decades. “So it’s always been a dream of mine to make these stimulators self-regulating.”
The electrodes implanted in the patients’ brains record signals from populations of neurons, not from individual brain cells, said Dr. Simon Little, an associate professor of neurology at UCSF who co-led the study with Starr.
“When neurons start to synchronize, when they start firing at the same time, they’re a little like a crowd at a sports game,” Little said, adding that in Parkinson’s and some other diseases, neurons become over-synchronized, with different patterns for different symptoms. “Some synchronization is good, but if it’s over-synchronized, if your entire network starts firing at the same time, then that’s an unhealthy state because the brain isn’t actually doing much information processing.”
The personalized system in the study reads signals from two different brain regions, delivering more electrical stimulation when patients enter a period of freezing and less stimulation when they begin a phase of involuntary movement — more stimulation when the drug levodopa is wearing off and less stimulation when the drug is working.
The study participants were men aged 40 to 60 who had been diagnosed with Parkinson’s disease at least six years earlier. They first had electrodes implanted in their brains and received regular deep brain stimulation for several months until they benefited most from it.
The researchers then began developing personalized algorithms for each patient, focusing on the symptom that bothered each patient the most. For three patients, including Connolly, that symptom was rigidity. For the fourth patient, it was involuntary spasms called dystonia.
Starr says the algorithm took two years to design for the first patient, in part because the stimulation itself changes brain signals and so had to be evaluated repeatedly. But for the fourth patient, it took just two weeks.
To test whether personalized stimulation improves patients’ experience, they are encouraged to “live as normal a life as possible,” Little said. “That could include skating, traveling, exercising.”
Every two to seven days over a two-month period, the system changed to deliver either conventional stimulation or personalized stimulation. Neither the patients nor most of the research team knew when which type of stimulation was delivered.
“Most of the previous studies were done in labs, which means they weren’t very practical,” Henderson said. “This was done under real real-world conditions, which is very impressive because it’s a very high bar. It’s very hard to do.”
Patients filled out daily questionnaires, and wearable monitors tracked changes in their movements. Little said three patients, including Connolly, speculated when they had received adaptive stimulation “because their symptoms improved.”
Starr says that for most patients, the duration of their worst symptoms decreased from about 25% of the day to about 12% of the day. Adaptive stimulation also reduced the severity of those symptoms. And, importantly, it did not worsen — and in some cases, it improved — “opposite” symptoms. (The “opposite” of stiffness, for example, is uncontrolled movement.)
One patient reported less time tolerating a third symptom, gait disturbance. Another patient, Starr said, was “very happy about the fact that his day started on time,” rather than spending hours feeling stiff and unable to start his morning activities. Three patients reported improvements in quality of life in areas such as mobility, pain and ability to perform daily activities. “The fourth patient is a happy person,” Starr said, who rated his quality of life highly from the start.
Connolly said he volunteered for the study in part because his wife, Thuy Nguyen, who died of cancer in 2020, encouraged him to try deep brain stimulation. “When my wife was sick and in the hospital, I would bring my skateboard and crutches, and I would skate some days and use my crutches other days,” he recalled.
During the research, Connolly and his wife founded a skateboarding program for children, and he arranged to take a break from the experiment because he wanted to avoid the experimental stimulus switch when he started a summer skateboarding camp.
He was able to recognize if he was switched to traditional or personalized stimulation because, he said, “I would feel good or dull almost immediately.”
He said the personalized algorithm also improved his sleep, which can be disrupted in people with Parkinson’s disease.
One problem with adaptive stimulation is that the algorithms need to be adjusted frequently because as patients’ “Parkinson’s disease progresses, they change medications, they change activities,” Starr said.
Three of the patients continued to receive adaptive stimulation after the study ended, but one had to pause for adjustments, Starr said. Connolly also plans to restart personalized stimulation after skate camp ends in the fall.
This article was originally published on The New York Times.
By Pam Bellec
Photo by Jason Henry
©2024 The New York Times
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