Essential tremor is the world鈥檚 most common movement disorder, affecting an estimated 7 million people in the U.S. alone. The hallmark of this disease is an involuntary, rhythmic shaking during intentional movement, complicating everyday tasks like writing, eating and drinking. When resting or sleeping, however, most patients have few or no symptoms.

The disease can be treated with a surgical procedure called , or DBS, where a neurosurgeon implants an electrode deep in the brain; this wire is then tunneled under the skin to a battery in the chest, which provides electrical stimulation that quiets the symptoms. In current use, however, these implanted devices are constantly 鈥渙n鈥� 鈥� delivering stimulation even when a patient doesn鈥檛 need it 鈥� which wastes valuable battery life.

For the first time, 91探花 researchers have combined electrodes on top of the brain to sense movement in the parts of the body that experience essential tremor, along with a deep brain electrode, to deliver stimulation only when it鈥檚 needed. The approach, developed by electrical engineers, 91探花Medicine researchers and ethicists at the at UW, is described in a to be published in a forthcoming issue of .

It鈥檚 an important step toward developing fully-implanted, closed-loop deep brain stimulators to treat disorders like essential tremor and Parkinson鈥檚 disease 鈥� devices that one day might be controlled by the patient鈥檚 own thoughts or movements.

鈥淲e鈥檇 ultimately like to give individuals that ability and choice,鈥� said co-author , a 91探花electrical engineering doctoral candidate and member of the CSNE team. 鈥淥ne side effect of deep brain stimulation can be difficulty speaking, for instance. So if you鈥檙e about to drink a glass of water, you might want to turn up the stimulation so your hand doesn鈥檛 shake. If you鈥檙e answering the phone, perhaps you鈥檇 want to turn it down so your speech isn鈥檛 affected.鈥�

Delivering deep brain stimulation also can extend the battery life of these implanted devices, which currently last only three to five years.聽 Lengthening battery life is important because replacing the battery requires surgery, which carries risks to the patient such as infection.

鈥淲e鈥檙e saving about half of the battery power, based on our subjects so far, which was one of our main motivations,鈥� said senior author and 91探花electrical engineering professor . 鈥淏ut even more interesting are some early indications that suggest our closed-loop system results in better patient performance, with less tremor, better control of their hands and fewer side effects.鈥�

In the video above, essential tremor patients drew spirals under three conditions 鈥� with their deep brain stimulator turned off (left), with the device constantly on (middle) and with the 91探花CSNE system that delivers stimulation as needed (right). In the latter two conditions, patients experienced significant and comparable relief from tremor symptoms that cause their hands to shake.

The project originated in a partnership between the CSNE and medical device manufacturer Medtronic to test new ways of with essential tremor patients. This system not only delivers electrical stimulation like traditional DBS systems, but also has the capability to sense and respond to electrical signals generated by the brain itself. The 91探花team received an investigational device exemption from the U.S. Food and Drug Administration for these tests.

To treat essential tremor, a surgeon typically implants an electrode in the thalamus of a patient鈥檚 brain. It鈥檚 wired down the neck to another implanted device housed under the clavicle that contains a battery and the electronics that drive the system. This 鈥渙pen-loop鈥� system, in clinical use today, delivers constant deep brain stimulation at levels set by a doctor.

In three patients who received the Medtronic Activa PC+S Deep Brain Stimulation system, 91探花Medicine surgeons also implanted a small strip of electrodes on top of the brain鈥檚 motor cortex, the part of the brain that controls movement. The electrode strip can be used to sense when a hand or other extremity affected by essential tremor is moving. In a key innovation, the team developed machine learning algorithms to 鈥渄ecode鈥� neural signals coming from the brain and correlate them with essential tremor symptoms that warrant treatment by stimulation.

The neural biomarkers and algorithms used to 鈥渄ecode鈥� them differ by disease. While a similar treatment approach has been documented for Parkinson鈥檚 disease, this is the first time neural signals have been used to selectively treat essential tremor.

鈥淭his is exciting both for treating those patients with essential tremor, but also for future uses,鈥� says , a CSNE team leader and neurosurgeon with the 91探花Medicine Neurosciences Institute.聽 鈥淭his represents the first time a person can control their implanted device through the voluntary use of brain signals. We now can see a direct path to all sorts of uses in stroke, paralysis or other neurologic conditions that may be treated in the future using this general approach.鈥�

Most essential tremor patients have symptoms only during intentional movement 鈥� when they move their arm to eat, drink or write, for instance. The 91探花CSNE closed-loop system detects that movement and only delivers stimulation to quiet the tremor symptoms when needed.

鈥淒BS results in some of my most grateful patients,鈥� said team member and co-author , a neurosurgeon at the 91探花Medicine Neurosciences Institute who implanted the devices. 鈥淭hey used to call this disease 鈥榖enign essential tremor,鈥� but it isn鈥檛 that benign. Patients don鈥檛 go out to eat because they spill food and drink. They stop having friends over because they can鈥檛 pour a cup of coffee. They can鈥檛 sign checks. They need help getting dressed. Regular DBS works really well to give people their lives back. What we are working on is taking a really good treatment and making it even better.鈥�

To test how well the systems worked, the research team asked the patients to perform simple motor tasks 鈥� such as drawing a spiral shape with a pen, writing sentences or trying to hold their hands steady 鈥� under three conditions: With their Medtronic implanted deep brain stimulator turned off, with the system that delivered constant stimulation and with the new system that only delivered stimulation as needed.

With no stimulation, the patients experienced tremor throughout the tasks. The effectiveness of the CSNE team鈥檚 new system in quieting the tremor symptoms was comparable to the open-loop system 鈥� but with greater energy savings.

In the experiments described in the paper, the computational tasks were performed on an external laptop next to the patient. Next steps include transferring that computational power to the device implanted in the patient鈥檚 chest wall 鈥� thus creating a fully-implanted, closed-loop deep brain stimulator. The team has received FDA approval to move onto the next step in real-world testing, which is sending patients home with their stimulators in closed-loop mode.

The research was funded by Medtronic, the National Science Foundation and the U.S. Department of Defense.

Co-authors include , a Medtronic biomedical engineer who joined the company after performing the research as a 91探花doctoral student and CSNE team member, and philosophy doctoral student , who at the CSNE in the .

For more information, contact Chizeck at chizeck@uw.edu. To reach 91探花Medicine co-authors, contact Susan Gregg at 206-616-6730 or sghanson@uw.edu

Grant numbers: NSF: EEC-1028725

Now, 91探花 researchers have demonstrated that when humans use this technology 鈥� called a 鈥� the brain behaves much like it does when completing simple motor skills such as kicking a ball, typing or waving a hand. Learning to control a robotic arm or a prosthetic limb could become second nature for people who are paralyzed.

“What we’re seeing is that practice makes perfect with these tasks,” said , a 91探花professor of computer science and engineering and a senior researcher involved in the study. “There’s a lot of engagement of the brain’s cognitive resources at the very beginning, but as you get better at the task, those resources aren’t needed anymore and the brain is freed up.”

Rao and 91探花collaborators , a professor of neurological surgery, and , a doctoral student in bioengineering, online June 10 in the .

In this study, seven people with severe epilepsy were hospitalized for a monitoring procedure that tries to identify where in the brain seizures originate. Physicians cut through the scalp, drilled into the skull and placed a thin sheet of electrodes directly on top of the brain. While they were watching for seizure signals, the researchers also conducted this study.

The patients were asked to move a mouse cursor on a computer screen by using only their thoughts to control the cursor’s movement. Electrodes on their brains picked up the signals directing the cursor to move, sending them to an amplifier and then a laptop to be analyzed. Within 40 milliseconds, the computer calculated the intentions transmitted through the signal and updated the movement of the cursor on the screen.

Researchers found that when patients started the task, a lot of brain activity was centered in the prefrontal cortex, an area associated with learning a new skill. But after often as little as 10 minutes, frontal brain activity lessened, and the brain signals transitioned to patterns similar to those seen during more automatic actions.

“Now we have a brain marker that shows a patient has actually learned a task,” Ojemann said. “Once the signal has turned off, you can assume the person has learned it.”

While researchers have demonstrated success in using brain-computer interfaces in monkeys and humans, this is the first study that clearly maps the neurological signals throughout the brain. The researchers were surprised at how many parts of the brain were involved.

“We now have a larger-scale view of what’s happening in the brain of a subject as he or she is learning a task,” Rao said. “The surprising result is that even though only a very localized population of cells is used in the brain-computer interface, the brain recruits many other areas that aren’t directly involved to get the job done.”

Several types of brain-computer interfaces are being developed and tested. The least invasive is a device placed on a person’s head that can detect weak electrical signatures of brain activity. Basic commercial gaming products are on the market, but this technology isn鈥檛 very reliable yet because signals from eye blinking and other muscle movements interfere too much.

A more invasive alternative is to surgically place electrodes inside the brain tissue itself to record the activity of individual neurons. Researchers at and the have demonstrated this in humans as patients, unable to move their arms or legs, have learned to control robotic arms using the signal directly from their brain.

The 91探花team tested electrodes on the surface of the brain, underneath the skull. This allows researchers to record brain signals at higher frequencies and with less interference than measurements from the scalp. A future wireless device could be built to remain inside a person’s head for a longer time to be able to control computer cursors or robotic limbs at home.

“This is one push as to how we can improve the devices and make them more useful to people,” Wander said. “If we have an understanding of how someone learns to use these devices, we can build them to respond accordingly.”

The research team, along with the headquartered at the UW, will continue developing these technologies.

This research was funded by the National Institutes of Health, the NSF, the Army Research Office and the Keck Foundation.

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For more information, contact Rao at rao@cs.washington.edu or 206-685-9141 and Wander at jdwander@gmail.com.