August 29, 2013 | by Darcy Blake | Before I had surgery, I didn’t understand that the programming for DBS might not be as fast as the flick of a switch. I’m not a type who endures discomfort well, so the lesson in patience is a challenge. My neurosurgeon Dr. Mark Sendrak at Kaiser Permanente Redwood City says there are hundreds of thousands of possible combinations in Deep Brain Stimulation programming. ”Time is the biggest factor here.”

How does DBS ever work? Even if I were to sequester Dr. Rima Ash, my movement disorder specialist at Kaiser  Permanente San Francisco to work on my programming on a daily basis, who is to say that she or I would be able to stand the back-to-back sessions necessary to get us there! I don’t mean to exaggerate, but each session is like a minor electrocution session. Well, not quite, but there is definitely the odd jolt to a few of the settings. And yet, the majority of DBS patients do improve, and they get such relief that they wouldn’t think of not having the surgery.

The Movement Disorder Specialist’s Miracle
A deep brain stimulation lead is made of thin, insulated, coiled wires with 4 electrodes at the tip, and delivers stimulation using either one electrode or a combination of electrodes. It is the combination of electrodes that is left to a movement disorder specialist such as Dr. Ash and it is her choice of selection that is miraculous.

I went away from the doctor’s office on my first programming visit thinking my tremor was over thanks to DBS, and then it returned. My thought was, maybe I over-stimulated electrode and “blew a fuse” so to say, by upping the voltage too much and too fast.

Voltage and Frequency
Voltage and frequency are not the same,” said Dr. Sabelman, the neuro-bioengineer on Kaiser’s DBS team. “Raising the voltage causes the stimulation pulse to travel farther, increasing the radius of a more-or-less sphere around the active contacts. You change the frequency to get cells to quiet down when they are still overactive at the first frequency you try. If you have exactly the right frequency, you should need lower voltage, but this is not a well-established rule. It might be that the cells that gave the immediate good result were right next to the DBS electrode, and they “didn’t like” the higher voltage – they could revert to being overactive, or they could die and some other less-effective cells replace them in the circuit. This is just a guess, since there is no way to look inside and see what is really happening.”

The object to “ramp up the juice,” isn’t the goal of DBS programming, but I’ve read that as time goes by, people slowly increase the frequency to maintain good results.

Stimulation and Inhibition
“The “stimulation” frequency for reducing tremor is actually down-regulating neuron firing rates, not increasing them,” said Dr. Sabelman. “The targets at which we aim the DBS electrode are hyperactive because of loss of regulatory control as dopamine-secreting neurons disappear. A frequency of 160-180 Hertz (around F below middle C on a piano) hits the overactive cells so often they go into a “refractory” state and stop firing, or at least slow down. If we want to actually stimulate cells (increase firing rates) we would try around 30 Hertz (B 3 octaves below middle C, the 3rd lowest key on a 88-key piano). So we should call it “Deep Brain Inhibition” instead of stimulation, but that name will never catch on,” said Dr. Sabelman.

“Inhibition” sounds better than “stimulation” for PD patients like myself who have had enough stimulation for a lifetime; just the same way Haydn is more restful to play than Czerny. But that is getting away from the point.

High Frequency, High Pulse Width and Voltage
The 4 electrodes can be zapped in different ways. When I go in for an appointment with Dr. Ash, we sit facing each other and she keeps a chart of all the different combinations of she tries on me. Some of those may include high frequency, high pulse width and voltage. For instance, with high pulse width, voltage (and current) fed to the load is controlled by turning the switch between supply and load on and off at a fast pace.

Time Lag for Results
The beneficial effects of stimulation can take weeks to months to be discernable, and it can be unclear at the time of the testing in the doctor’s office what stimulation amplitudes, pulse durations, and frequencies will be effective for PD patients after a period of time.

VIM, GPi, and STN
Different sites of stimulation provide different clinical effects in PD. The Vim is the target of choice for Essential Tremor. VIM stands for Ventral Intermediate Nucleus of the Thalamus. Stimulation of the GPi, the Globus Pallidus pars interna may reduce the major motor problems of PD, including the reduction of dopa-induced dyskinesias. STN, Sub thalamic Nucleus, is an effective therapy for bradykinesia, stiffness, and tremor, some of the motor symptoms of Parkinson’s disease. STN is in part of the Basal Ganglia (the motor circuit of the brain). “We now use both the STN and GPI for Parkinson’s disease, and they are both equally effective,” said Dr. Ash. “The main differences between the two are that people are unable to reduce meds as much with GPi, however GPi tends to be more gentle in those with a history of depression/anxiety (STN can sometimes worsen anxiety/depression or impulse control).”

Sensitivity Depends on Amplitude, Cells, Field, Elements and the Disease
The sensitivity of different elements depends on the amplitude of the stimulation, physiologic properties of individual cells, geometry of the stimulus field, and stimulated elements, and conditions of the disease itself.

In the Hands of a Master Puzzle Solver
The bottom line here is that the job of a movement disorder specialist is like a master puzzle solver who is given a thousand puzzle pieces. It reminds me of the scientists at the Physics Institute at the University of Padua, who developed a technique to recreate 15th century Andrea Mantegna frescoes that were pulverized in the second world war at Ovetari Chapel of the Eremitani in Italy. Scientists recreated the frescoes from 88,000 surviving fragments, using a set of black-and-white photographs of the chapel taken in the 1920s. The photos and fragments were compared by a special computer program using a process mathematicians call “Circular Harmonic Decomposition,” that left out the intricate rotation of each fragment, but still delivered a list of possible positions for them, complete with a probability rating for the chances of conformity.

If only such smart algorithms would work on a brain, we could get to the bottom of the thousands of possibilities for impulse programs quickly. Dr. Sabelman says, “There are deconvolution algorithms for sorting nerve cell firing patterns (called “spike sorting”) which are mainly used in research; they don’t seem to add enough information to try them in the real-time OR environment.” If only it were as easy as that.

My job is to have faith in my doctor, like all the patients before me, because most patients do finally find improvement. So now at 6 weeks post surgery, I’m “keeping the faith,” as I take my walking sticks out for tremor relief. It will all work out, one program at a time. It is too early to say, but the tremor just may be somewhat better.

icslwebs.ee.ucla.edu/dejan/researchwiki/images/2/23/Mink06.pdf  Deep Brain Stimulation, by Joel S. Perlmutter and Jonathan W. Mink, Copyright  2006 by Annual Reviews.



Many thanks to my neurosurgeon, Dr. Mark Sedrak, my Movement Disorder Specialist, Rima Ash, and the neuro-bioengineer, Dr. Eric Sabelman, at Kaiser Permanente, Redwood City, and San Francisco for their medical consultation on this blog.

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