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Clues to How an Electric Treatment for Parkinson’s Works

Thursday April 16, 2015

Carl Zimmer

New York Times - In 1998, Dr. Philip A. Starr started putting electrodes in people’s brains.

A neurosurgeon at the University of California, San Francisco, Dr. Starr was treating people with Parkinson’s disease, which slowly destroys essential bits of brain tissue, robbing people of control of their bodies. At first, drugs had given his patients some relief, but now they needed more help.

After the surgery, Dr. Starr closed up his patients’ skulls and switched on the electrodes, releasing a steady buzz of electric pulses in their brains. For many patients, the effect was immediate.

“We have people who, when they’re not taking their meds, can be frozen,” said Dr. Starr. “When we turn on the stimulator, they start walking.”

First developed in the early 1990s, deep brain stimulation, or D.B.S., was approved by the Food and Drug Administration for treating Parkinson’s disease in 2002. Since its invention, about 100,000 people have received implants. While D.B.S. doesn’t halt Parkinson’s, it can turn back the clock a few years for many patients.

Yet despite its clear effectiveness, scientists like Dr. Starr have struggled to understand what D.B.S. actually does to the brain.

“We do D.B.S. because it works,” said Dr. Starr, “but we don’t really know how.”

In a recent experiment, Dr. Starr and his colleagues believe they found a clue. D.B.S. may counter Parkinson’s disease by liberating the brain from a devastating electrical lock-step.

The new research, published on Monday in Nature Neuroscience, may help scientists develop better treatments for Parkinson’s disease. It may also help researchers adapt D.B.S. for treatment of such brain disorders as depression and obsessive compulsive disorder.

To treat Parkinson’s disease, neurosurgeons insert electrodes into a region called the basal ganglia, near the base of the brain. The disease kills a small patch of neurons in the basal ganglia that normally produce a neurotransmitter called dopamine.

In the early days, some scientists thought that D.B.S. worked by shutting down neurons that were malfunctioning because of a lack of dopamine. But later experiments revealed this was not the case. So scientists began looking at other ways in which Parkinson’s disease changes the brain.

Among other things, the condition alters the brain’s electrical rhythm. The brain normally produces a set of electrical waves at different frequencies. One of these waves, called the beta rhythm, has a distinctively low frequency of between 13 and 30 cycles each second.

A number of studies suggest that the beta rhythm serves an important purpose: It keeps the different regions of the brain synchronized, like the sections of an orchestra.

Each time the brain reaches the crest of a beta rhythm, scientists have found, neurons get primed to send their signals. By coordinating these signals, the beta rhythm may keep distant regions of the brain on the same timetable.

“It makes communication more efficient,” said Coralie de Hemptinne, a post-doctoral researcher at the University of California, San Francisco, and co-author of the new study.

The strength of beta rhythms can also change, scientists have found, becoming stronger or weaker. The stronger beta rhythms get, the more overpowering they become, forcing more neurons to fire in unison. If beta rhythms become too strong, the regions of the brain may get stuck in a sort of neural lock-step, unable to disengage from one another to generate new signals.

“If you don’t have it, that’s bad, but if you have too much of it, that’s also bad,” said Bradley Voytek, a neuroscientist at the University of California, San Diego, who was not involved in the study.

To take a step or reach for a doorknob, the brain first generates commands in a region called the motor cortex. Before the motor cortex generates commands, scientists have found, its neurons become desynchronized. That shift may allow the motor cortex the freedom to produce new electronic messages.

When people get Parkinson’s disease, the synchronization of the beta rhythm becomes stronger throughout the brain. Dr. Starr and his colleagues wondered if this change might give rise to some of the symptoms of the disease.

To find out, the scientists planned out a series of experiments during surgeries to implant D.B.S. devices. They temporarily placed a strip of sensors on the motor cortex and eavesdropped on the signals coming from neurons in different parts of that region of the brain.

The scientists found that in people with Parkinson’s disease, parts of the motor cortex were more tightly synchronized than in people without the disease. This lockstep might help account for the problems people with Parkinson’s disease have with movement: Perhaps it’s hard for their brains to break out of synchronization and to generate a new pattern of signals that can start moving the body.

Dr. Starr and his colleagues suspected that D.B.S. affected this synchronization in people with Parkinson’s. In another round of surgeries, the scientists monitored the motor cortex before people’s implants were switched on, and then listened to it afterward.

They found that D.B.S. caused the motor cortex to become less synchronized.

Dr. Starr’s patients remained conscious during the surgery, so he and his colleagues were able to test their movements. The patients reached out to touch dots that appeared on a touch screen placed in front of them. Their motor cortex became less synchronized as their movements improved.

“Starr’s work is excellent,” said Michael S. Okun, a professor of neuroscience at University of Florida Health and the national medical director of the National Parkinson Foundation.

But while synchronization may well cause some Parkinson’s symptoms, he added, it probably doesn’t account for all of them: “A whole bunch of biology happens in Parkinson’s.”

Dr. Voytek said that the new study could lead to better implants. Current devices send out a constant buzz. It might be better to design implants that only deliver a pulse when the brain becomes too synchronized. “This is paving the way for smart neurotransmitters,” said Dr. Voytek.

The new research might also explain why D.B.S. is yielding some promising results as a treatment for conditions such as depression and obsessive compulsive disorder. Too much synchronization may be able to disrupt the brain in many ways — and D.B.S. may help break the pattern.