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December 3, 2011

Deep Brain Stimulation - A Different Approach


Let's talk about Parkinson's Disease (PD). PD is one of the most prevalent neurodegenerative disorders in the world for people over the age of fifty; as the population has aged and people have started living longer, PD diagnosis has increased significantly. Some of the symptoms include tremor (shaking), akinesia (inability to initiate movement), muscle rigidity, and later in the progression of the disease, slowed speech, blank staring, and dementia. So there are motor and cognitive problems associated with PD, but this post will deal with the reduction of the earlier-onset motor symptoms.

There are two main types of treatment for PD motor symptoms: drugs and deep brain stimulation (DBS). The drugs usually have a compound called L-Dopa, which is a precursor in the formation of the neurotransmitter dopamine, the lack of which has been implicated in inducing the motor symptoms of PD.

The other treatment, DBS, can only be used on some patients, namely those for whom the drugs have had little to no effect and who are also healthy enough to undergo surgery and stay alive for longer than a few years. What they do is create an open-loop (i.e. not a closed circuit) by surgically inserting an electrode into a specific region of the brain, which is connected to a pacemaker-type device called a pulse generator (IPG) that they insert below the neck. Doctors then set the IPG to a certain frequency, so the electrode will send out electrical signals into the brain every so often, and this has been shown to reduce the motor symptoms of PD.

The whole process takes up to a year, with the surgery and adjustments to the properties of the stimulation being continuously modulated until the motor symptoms are reduced and the side effects of the stimulation are not too severe. But, since PD is a progressive disease, the motor symptoms will continue getting worse and the DBS stimulation will continue to need adjustments more and more frequently as the disease progresses.

The issue with this is that no one really knows why DBS works, so all of the adjustments are guesses (systematic guesses, but guesses nonetheless) and patients need to keep coming into the hospital, which costs a lot of money, time, and frustration when their symptoms are not relieved. This is where research in the "closed-loop," or real-time adaptive, DBS comes in. This potential form of DBS also involves a chip that is used to record when natural electrical signaling occurs in the brain region the DBS electrode is in. The recording then sets the properties of the DBS stimulation on the IPG and sets a timer for when the electrode will deliver that stimulation, producing a feedback loop, and decreasing the need for the constant hospital visits.

One study found that given some specific criteria for the wait-time and the number of stimulations, some PD symptoms were reduced (namely akinesia) to a greater extent than with open-loop DBS. However, the study also found many problems with using closed-loop rather than open-loop DBS to alleviate motor symptoms, but these problems have to do with what actually causes the motor problems associated with PD. As such, the study concludes that with more research on the efficacy of closed-loop DBS and on the details of the cause of PD motor symptoms, closed-loop DBS could be used as a potential treatment for PD that will produce not only a more significant reduction of motor problems, but will also enhance the long-term efficacy of using DBS as PD progresses.

Rosin, B., Slovik, M., Mitelman, R., Rivlin-Etzion, M., Haber, S. N., Israel, Z., . . . Bergman, H. (2011). Closed-loop deep brain stimulation is superior in ameliorating Parkinsonism. Neuron, 72(2), 370-384. doi:10.1016/j.neuron.2011.08.023 Retrieved from http://www.cell.com/neuron/abstract/S0896-6273%2811%2900776-8
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