Biology 202

2006 Second Web Paper

On Serendip

It seems that this "bowl of soup" vision of the brain, where large changes can occur by adding different "seasoning" chemicals, cannot be entirely true. A recent advance in brain technology called deep brain stimulation has demonstrated that the brain may in fact be able to be influenced simply by the stimulation of a small area, and that different parts of the brain in close proximity can control different aspects of the same disease. This presents a more complicated picture of the brain, where it is only the specific interaction between each infinitesimal part that causes a "normal" functioning, and that a small error in the patterns of one can disrupt the delicate workings of the brain. Large scale treatments that attempt to effect the entire nervous system with a wash of chemicals may be entirely too broad to affect an advanced level of change and control.

In deep brain stimulation (DBS), a small metal electrode is inserted into the brain region that is overactive and is attached to an Implantable Pulse Generator (IPG) located under the skin of the chest that controls the strength of the stimulation(1) like a pacemaker. This procedure was invented in France in the 1980's (3) but did not become approved by the Federal Drug Administration until recently. Each of the different targeted sites for DBS can help to abate particular symptoms. Stimulation can be done to the thalamus, the global pallidus, and the subthalamic nucleus and is adjustable and reversible(3).

Thalamic stimulation became the first approved types of DBS for Parkinson's in 1997 (1) and has been shown to cause a significant improvement in tremor and the ability to initiate upper-extremity movement (akinesia) (4) over drug-only conditions during a long-term study. Often this procedure is performed bilaterally and is considered much more safe than a bilateral thalamotomy, where the thalamus is irreversibly lesioned. (3). Thalamic stimulation occurs in the ventro-intermediate nucleus and causes a reduction or suppression of tremor in 80% of patients who are treated and follow up over ten years shows a control over tremor that remains constant over time(3). The region it stimulates is very particular for the single symptom of tremor, showcasing the specificity of this section of the brain. It is suggested that this option is best for patients with longstanding, non-progressive tremor-dominant Parkinson's, such as those who are elderly(4).

Stimulation of the global pallidus (GPi) can be used for treatment for both dyskinesia and rigidity issues in Parkinson's patients(3). It gives benefit to 70-80% of recipients, though sometimes it can worsen bradykinesia in those who have received it(3). Much more effective is subthalamic stimulation (STN). With this type of stimulation there can be reductions of rigidity and tremor in only seconds, with movements improving after a few hours(5), can have effects on postural stability, freezing, and gait, and often causes a significant reduction of L-dopa dosage(3). An early study reported a mean 58% increase in motor function, with over 50% improvements in akinesia, rigidity, and gait and balance, as well as an 82% reduction of tremor(6). Incredibly, it was also shown that there was a 17% improvement in the "stimulation-off" state, a possible result of the electrode insertion or a carry-over of chronic stimulation(6). Later research showed a 52.5% increase in mean gait velocity and stride length, as well as a larger range of motion and a decrease in forward trunk inclination(7). This type of procedure is preferred because of increased safety, what is thought to be the highest reduction in anti-Parkinson drug use, and a lower stimulation voltage needed, leading to a longer battery life in the IPG(3). It is thought that GPi is best for patients with dose-limiting dyskinesia, while STN is more helpful for younger patients who have prominent bradykinesia(8).

Deep brain stimulation for Parkinson's disease can affect the lives of many people who are living with debilitating symptoms. The results of these studies offer an interesting contrast to what scientists have "always known" about brain disorders: that they are caused and controlled by an increase or decrease in a particular neurotransmitter, and so the best way to treat the symptoms is to give a drug that floods the brain with replacements. This new treatment flies in the face of conventional ideas. It shows that a more specific method of treatment where a particular location of the brain is stimulated can be drastically more effective than a blind dumping of neurochemicals into the entire brain. Brain function can not be a simple as a mere change in transmitter amount. DBS has no effect on the substantia nigra, where damaged cells stop producing dopamine. Instead its effects are on small areas of the brain, each able to help abate different symptoms. It is also important to note that currently there is no one location that can be subjected to stimulation and miraculously cure all Parkinson's symptoms. Just as this disease is not simply a lack of dopamine (and could be cured by medications), it is not a result of overactivity in just one area of the brain. The actions of the brain are much more complex than a simple cause/effect. There is a complex arrangement of neuron activity that must cause these symptoms; otherwise symptom alleviation would be easy: just find the cause (a lack of dopamine, perhaps?) and replace the missing piece. The effects of deep brain stimulation in Parkinson's offer many interesting ideas about the future of neurological treatment. It has already been shown to have positive effects in ending severe depression(9) and holds great promise for treatment of other diseases. The concepts associated with this treatment challenge the common perceptions that the brain simply an amalgam of chemicals and will hopefully lead to a revolution of current neurological treatments.

1)About Parkinson's Disease, a broad description of the disease from the National Parkinson's Foundation.

2) Witjas T. "Deep Brain Stimulation can cure dopamine addiction." Pain and Central Nervous System Week. 24 October 2005 p 194.

3)Deep Brain Stimulation, a PDS Information Sheet, a handout from the Parkinson's Disease Society of England.

4) Tarsy D et al. "Progression of Parkinson's Diesease following Thalamic Deep Brain Stimulation for Tremor." Stereotactic and Functional Neurology 2005 (83) 222-227.

5)Deep Brain Stimulation-Latest Research, information from the Parkinson's Disease Society of England.

6) Kumar R et al. "Double-blind evaluation of Subthalamic Nucleus Deep Brain Stimulation in advanced Parkinson's disease." Neurology 1998:51(3). 850-855.

7) Rizzone M et al. "High-frequency electrical stimulation of the subthalamic nucleus in Parkinson's disease: kinetic and kinematic gait analysis" Neurological Science 2002:23. S103-S104.

8) Anderson V et al. "Deep Brain Stimulation in Parkinson Disease Reduces Uncontrolled Movements" Journal of the American Medical Association. 17 April 2005.

9) A Depression Switch, an article by D. Dobbs from the New York Times Magazine, 2 April 2006.


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