Over the last decade, deep brain stimulation, in which an implanted electrode delivers targeted jolts of electricity, has given surgeons an entirely new way to treat challenging neurological diseases. More than 75,000 people have undergone the procedure for Parkinson’s and other disorders. But despite its success, scientists and surgeons know little about its actual effect on the brain or exactly why it works.
An implantable sensor designed to detect vital chemical signals in the brain, currently being tested in animals, could help scientists measure the impact of electrical stimulation and perhaps provide a way to enhance the effectiveness of the treatment. “For a long time in neurosurgery we’ve been dealing with the brain from purely an electrical perspective,” says Nader Pouratian, a neurosurgeon at the University of California, Los Angeles, who was not directly involved in the research. “This allows us to look at the brain as an electrochemical organ and understand the effect of interventions such as deep brain stimulation.”
During the conventional deep brain stimulation procedure, neurosurgeons insert a small electrode into the brain. The patient is awake during the surgery so that the surgeon can find the optimal location and level of stimulation to reduce the patient’s symptoms. In Parkinson’s patients, for example, muscle tremors are often immediately and visibly reduced with the appropriate stimulation.
However, the actual mechanisms behind its therapeutic effect are hotly debated. Recording the release of the brain’s signaling chemicals, known as neurotransmitters, could help to resolve the question, allowing neurosurgeons to better optimize the procedure.
The device consists of a custom-designed sensor electrode that is implanted along with the stimulating electrode, a microprocessor, a Bluetooth module to send data to a computer, and a battery. “It allows us to record dopamine and serotonin wirelessly in real time,” says Kendall Lee, a neurosurgeon at the Mayo Clinic, Rochester, MN, who helped develop the device. “That means we have tremendous control over the chemistry of the brain.”
To detect neurotransmitters, researchers apply a low voltage across the electrode. That oxidizes dopamine molecules near the electrode, triggering current flow at the electrode. “The amount of current flow gives a relative indication of concentration,” says Kevin Bennet, chairman of the division of engineering at the Mayo Clinic and one of Lee’s collaborators.
Preliminary research in pigs using the new system has shown that deep brain stimulation of the area targeted in Parkinson’s patients triggers release of dopamine. Researchers now aim to repeat these experiments in pigs that have some of the symptoms of the disease. For example, the sensors could detect whether certain patterns of dopamine correspond to improvements or worsening of Parkinson’s symptoms.
“We have to get more nuanced understanding of how electricity impacts brain chemistry at the microscopic circuit level,” says Helen Mayberg, a physician and neuroscientist at Emory University, in Atlanta, who was not involved in the research. “This type of technology gives us the opportunity to look precisely at very local changes in the chemical mix. As the technology is expanded to be able to detect an even wider range of neurochemical systems, it’s going to really catapult what we can learn about the mechanisms of brain stimulation and the diseases we treat with it.”
In addition to detecting dopamine, preliminary research shows the technology can also detect serotonin, a brain chemical implicated in depression. (Serotonin reuptake inhibitors such as Prozac target this neurotransmitter.) Deep brain stimulation is currently approved to treat Parkinson’s, the movement disorder dystonia, and severe obsessive-compulsive disorder, and is under study for epilepsy, depression, anorexia, and other disorders.
Lee says his team has now been granted approval to test the system in a patient, which they aim to do in the next few months. Initially, it will be tested only during the implantation surgery to determine how moving the electrode alters the level of dopamine released. But the ultimate goal is to incorporate the sensor into the deep brain stimulation system. Researchers are currently developing new sensor electrodes that function effectively over the long term, as well as shrinking the device so that it can be packaged and implanted onto the skull. Once researchers better understand the link between deep brain stimulation and neurochemistry, the accompanying chemical data may help neurosurgeons to better place the electrode.
But some say this step may be premature. “The technology is very intriguing, but we need a lot more research before it can be applied in humans,” says Ali Rezai, a neurosurgeon at Ohio State University, who was not directly involved with the research. He says that researchers need to show that using this technology alongside deep brain stimulation in animals with symptoms of Parkinson’s disease improves outcomes.
In the long term, Lee and his collaborators want to develop a so-called closed loop system, allowing the stimulation device to detect the chemical changes in the brain and adjust its response accordingly. This approach is analogous to cardiac pacemakers, which stimulate the heart only when the instrument detects an abnormality. While abnormalities in heart rhythms are fairly straightforward to detect, “in the brain, it’s much more complicated,” says Rezai.