Adaptive Deep Brain Stimulation to Ameliorate Parkinson’s Disease

by Jennifer Cortes

Parkinson’s Disease (PD) is a progressive neurodegenerative disease for which there is currently no cure. Approximately 7-10 million people worldwide are affected with PD. As with most neurodegenerative diseases, age is the biggest risk factor for developing PD; the average age of onset is 60 years. The World Health Organization predicts that between 2000 and 2050 the proportion of people over the age of 60 will double from 11 percent to 22 percent. Therefore, we can expect an increase in the incidence of PD in the years to come. Traditional drug therapy is limited and will not be able to meet the demands imposed by a growth in the number of affected individuals. However, a recent advancement in deep brain stimulation (DBS)—using biofeedback from a brain computer interface—may prove to be an effective solution.

So what exactly is PD? PD is characterized by four cardinal symptoms: (1) bradykinesia/akinesia, which refers to slowed movement or the lack of it; (2) tremor (often at rest); (3) lack of coordination; and (4) cogwheel rigidity, which describes jerky movements around a joint. These motor symptoms are primarily caused by the destruction of brain cells in the substantia nigra that produce dopamine, which is a neurotransmitter responsible for sending signals to other nerve cells to control movement and coordination. This dopamine deficiency in turn causes the subthalamic nucleus—a key modulator of basal ganglia output—to send the abnormal signals that cause the movement problems associated with PD.

Traditional treatment relies on medications that increase dopamine levels; their effectiveness, however, is limited and temporary. As a result, patients may constantly visit their doctors to adjust the dose of their medication or to switch to another medication, placing a burden on both the patient and their caregiver. Short of having a pallidotomy or a thalamotomy—that is, short of surgically destroying brain tissue—the only other alternative treatment is DBS.

DBS uses a device called a neurostimulator that is surgically implanted. A neurostimulator can be compared to a heart pacemaker both in terms of function and size, and it blocks abnormal signals that cause the motor symptoms of PD. Most patients with DBS see improvements in their motor symptoms and many can reduce their amount of medications. The use of DBS is currently restricted though by its cost, limited effectiveness, and side effects that include deterioration of speech and cognitive functions. The DBS devices presently used send out a continuous high-frequency signal to the subthalamic nucleus, despite the fact that PD symptoms fluctuate. This inefficient power usage results in the need for periodic surgeries to replace the battery of the neurostimulator and increase the risk of side effects due to overstimulation. Brain computer interfaces have the potential to make DBS a more viable option for PD treatment by making the technology “smarter.”

Brain computer interfaces (BCIs), also known generally as brain machine interfaces (BMIs), allow a user to communicate with an external device using brain signals. The most well-known applications of BCIs were conceived to give paralyzed individuals the independence to move computer cursors, control wheelchairs, or move prosthetic arms among other things through their thoughts. Now, BCIs have the potential for a wide range of clinical applications. In general terms, BCIs record electrical signals that are then interpreted by a computer and translated to perform an intended action.

Peter Brown, M.D., and his team of researchers at the Nuffield Department of Clinical Neurosciences at the University of Oxford demonstrated that BCI-controlled adaptive DBS (aDBS) can be used to interpret brain activity in PD patients and control when stimulation is delivered. More specifically, the BCI would monitor the effect of each signal it sends out and adjust the strength and timing of its signal accordingly. In other words, adaptive DBS only sends out a signal when the BCI detects abnormal activity sent by the subthalamic nucleus. In their study, aDBS was tested in 8 PD patients and the results showed that motor skills improved with aDBS by 29 percent more than the improvement seen with traditional continuous stimulation, while reducing the stimulation time by 56 percent.

The implications of these results are tremendous. Because stimulation is controlled with aDBS, the battery that powers the neurotransmitter would last longer than the current range of two to five years. This in turn would translate to a reduced frequency with which patients would have to undergo surgery to replace the battery, thereby minimizing the risk of surgical complications and infection. Additionally, reducing the amount of electrical stimulation could possibly lower the risk of side effects, although further research is necessary to confirm this. Furthermore, the longer life-span of the battery would be one step towards making DBS a more cost effective option. To have the battery replaced costs between $10,000 and $20,000, plus the surgery. Even if the battery life were to be increased by just one year, cumulatively it would make an enormous difference over the span of 20 years.

The future looks bright for PD treatment if research in BCI-controlled aDBS continues. Research is still young in this area, but the benefits are already proving to be grand as we enter the new age of personalized and “smart” medicine.