I’m not saying that Parkinson’s Disease is all in your head, at least not in the colloquial sense. But in the literal sense, PD is most definitely a dysfunction in your brain, even if it is your body that shows the symptoms.
So maybe this idea is not as crazy as it first sounds…
I’m not a doctor. I’m not a scientist. I am a computer software developer who was diagnosed with Parkinson’s Disease 4-1/2 years ago. I have a tendency to view PD as a complex system problem occurring within the brain. Without access to the source code, it is an impossible challenge to debug.
If it were truly software, PD would be characterized as a heisenbug. A heisenbug is a software bug that changes it’s behavior when you try to study it. Symptoms appear in one area, then move elsewhere. Some days are a lot better or worse than others for no apparent reason. Researchers find clues, but are they cause or effect? (For those of you who are fans of quantum mechanics, heisenbug is a play on words relating this type of problem to Heisenberg’s uncertainty principle.) (And for those of you who are software developers, I suspect uninitialized variables, excessive recursion and insufficient stack space.)
Billions of dollars of research have been spent to identify what causes Parkinson’s Disease, and maybe we’re getting closer. The prevailing wisdom is that PD likely is multiple, possibly dozens, different disorders which end up affecting the same area of the brain.
I’ve seen and heard a lot of speculation that PD could be caused by the interaction of environmental and genetic factors. Our genes determine a lot of the chemistry within our brains, and it is conceivable that people with different genetic combinations may be more susceptible to various environmental toxins. It is also possible that some non-toxic environmental compounds could become toxic under certain conditions.
What we do know about PD is that the debilitating effects of PD are caused by a lack of the neurotransmitter dopamine in a particular area of the brain, which leads to tremors and difficulty initiating movement. Prevailing wisdom is that by the time PD is diagnosed, more than half of the dopaminergic neurons in the substantia nigra are no longer functioning, leading to a severe deficiency of dopamine in the stratium. Dopamine is the neurotransmitter used to relay messages to initiate and control movement, and the dopamine deficiency causes the motion disorders characteristic of PD.
We don’t know for certain what is happening to the dopaminergic neurons. But we do know that the movement problems that characterize PD are a lack of dopamine. Various prescription drugs are used to help these movement problems. Carbidopa levodopa (Sinemet) is a combination of carbidopa and levodopa. Levodopa (L-dopa) is a precursor that the brain can easily convert to dopamine, and carbidopa is combined with it to help the levodopa cross the blood brain barrier, so that it is delivered to the brain. There are also dopamine agonists, which are chemical compounds that bind to receptors in the brain and act like dopamine. There are also MAO and COMT inhibitors. MAO and COMT are enzymes that break down dopamine after it has been used, inhibiting these enzymes can help dopamine that has been produced to last longer.
It is important to note that all of these drugs provide only symptomatic treatment, they do not stop or delay the progression of Parkinson’s Disease.
Personally, I was a bit skeptical about dopamine being so central to PD. My experience with taking a dopamine agonist was that it had very little impact on my motor function. I exercise hard almost daily, and whether or not I remembered to take my pill had little effect. Switching over to L-dopa also showed minimal effect. Then I decided to try a different neurologist (motion disorder specialist) who said I was under-medicated, and encouraged me to gradually increase my dosage up to a certain point to find the level that worked best for me.
Wow is all I can say. After 4 years of living with PD and thinking I was doing well, I began to realize differences…mostly differences in my exercise abilities. There were a few exercises that I had simply not been able to perform. Boxing battle ropes – I could move them with great force in unison, but struggled to move them in alternating fashion. Rapid kicks with my left side were ok, but rapid fire kicks with my right side were an exercise in frustration. After increasing my L-dopa dosage, I began improving in exercises that I had been trying, but failing at, for years. This morning is a perfect example. I was actually faster and more powerful with right side kicks than my left side. 10-15 consecutive jumps with a jump rope have become 30-50, and I reached a new personal best this morning of 80.
All of this has me thinking a lot about dopamine.
Outside of the PD community, dopamine has a reputation for being known as the pleasure chemical. But, in reality, research has shown that it is the anticipation of a pleasurable reward that actually causes dopamine to be produced. Robert Sapolsky’s research with primates provides an interesting perspective on dopamine production. He provides a quick summation in the following video:
The interesting take-away is that more dopamine is produced in anticipation of a reward than by receipt of the reward. In the research that Sapolsky is discussing, there was a trigger event that preceded a reward. Once the primate began to associate the trigger with the reward, the researchers could measure that more dopamine was produced by the trigger than by the reward. In other words, it was anticipation of the reward that was responsible for more dopamine production.
They took the test a step further…what happens if the trigger event does not always lead to the reward, but only sometimes produces a reward? The uncertainty in the resultant anticipation produced even higher levels of dopamine, whether or not a reward was forthcoming. The highest levels of dopamine were observed when there was a 50-50% reward chance.
Keep in mind that this was a primate study, and humans may have a higher tolerance to wait longer for a reward. Sapolsky’s book “Behave: The Biology of Humans at Our Best and Worst” describes this as delayed gratification. For example, we are willing to work hard to get into a good school, to get a good job, to buy a nice house, and earn enough money to afford to send our kids to a good school. Instead of the pursuit of happiness, we produce dopamine through the happiness of pursuit.
This area of study provides some interesting behavioral insight to consider with regard to addictions, most notably gambling addiction… but also sexual addiction, drug addiction, and even shopping addictions.
An interesting study of gambling addiction explored the near miss effect, when 2 of the 3 wheels line up in a slot machine. Control subjects produced minimal dopamine after any type of miss, but those with a gambling problem saw intense dopamine release for a near miss. This near miss effect might even explain my mother-in-law’s reputation for frequently purchasing an item in a store, only to return it the next day.
We all have different interests and motivations that fuel our dopamine production. I’ve had fascinating discussions with friends, explaining dopamine, and talking about their passions, motivations, and in some cases, their addictions. I’m starting to think that dopamine, and the pursuit/anticipation of reward is central to our existence.
Interesting stuff…but what does this have to do with Parkinson’s Disease?
Well, one of the most common side effects of PD medications is addictive behavior, such as gambling, hyper sexuality, obsessive involvement with new hobbies. These side effects are most common with dopamine agonists, which act like dopamine, but fool the brain’s reward anticipation circuitry, leading to unusual addictive behavior.
This connection between PD medications and addictive behaviors makes it very clear that there is dopamine involvement in both the anticipation/reward process and basic motor function.
What if…in some cases, the cause of low dopamine has a psychological origin or trigger?
When we talk about human genetics and behavior, there is the debate of “nature vs. nurture”. How much of our personality traits come from our genes, and how much is acquired from the environment in which we were raised.
Take notice of my use of the word environment in the previous paragraph. Earlier in this essay, I mentioned the common theory that PD could be caused by the interaction of environmental and genetic factors. Do these environmental factors necessarily have to be physical, or could they be either physical or psychological as implied in the “nature vs. nurture” debate.
Studies have shown that combat veterans suffering from Post Traumatic Stress Disorder (PTSD) experienced physical changes in their brain (atrophy of the hippocampus) as a result of an extremely traumatic stressful experience.
I don’t want to belittle the plight of brave men and women who suffer the plight of PTSD. But, could other experiences have different physical effects within the brain, and could the consequences of these physical changes have differing impact depending on our genetic composition?
Consider me, as a potential example…
I’ve always been motivated and focused…hard working, driven, and eager to learn new technologies.
I started and ran a software business for over 10 years. There were countless all-nighters spent creating new products or adapting products for another market, as dopamine fueled my pursuit. But it was also stressful. There were business partners who burned out and had to be bought out. But it was a constant dopamine rush…some great years that I sometimes miss. The timing eventually was right for me, and I had an opportunity to sell the business.
A year or so later, I started a new software venture that kept me pursuing new technologies, but avoiding the stress of running a business and managing employees. Fast forward another 10 years later, and I was clearly bored. I plodded along making minor changes to the existing software. Outside of work, life was comfortable and my family well provided for, so I didn’t feel the pressing need to innovate. Work was no longer challenging, and I was out of worthwhile new ideas to pursue.
Some might call this depression, but I think it is different. PD or not, I continue to have an extremely optimistic outlook on life in general. But most days, I do have an apathetic feeling toward my work…and for that matter, my primary hobby, which was this work.
From a dopamine perspective, for many years, writing programming code and solving complex problems…or rather than anticipation of solving each and every constant challenge, kept me producing dopamine.
Is it unrealistic for my brain, on some level, to just not see the need to produce so much dopamine any more?
I suppose that a neurologist could argue that my lack of motivation and apathy toward my work are a result of low dopamine caused by Parkinson’s Disease. But I don’t think so. I am inclined to see a strong possibility that my dopamine system is dysfunctional from years of overuse followed by years of underuse…a cerebral midlife crisis, if you will.
I’m grossly oversimplifying the issues. But, I think an argument can be made that when we look at potential environmental triggers of PD, psychologically induced changes to the brain may sometimes be involved.
Is that the case for me? Who knows. Over the past few months, I’ve been concentrating more on trying to better understand my motivations and anticipations, and making the most of my dopamine while I still can. As the old saying goes, “If you don’t use it, you lose it.”
However, if the truth is to be told…when I think about it, the 4-1/2 years since my PD diagnosis have actually been some of the best years of my life.