Parkinson’s Background and Prevalence

Parkinson’s is a progressive neurodegenerative disorder that affects movement. As a result, those with Parkinson’s tend to have debilitating symptoms such as tremors, slowed movement, rigid muscles, and writing changes¹. When looking at the population as a whole, over ten million people are living with Parkinson’s Disease, and these numbers are rising as a result of aging populations, increasing longevity, declining smoke rates, and a by-product of industrialization². In a study, it was noted that there is a great correlation between age increase and an increase in motor rate progression, decreased levodopa responsiveness, postural impairment, worsened gait, and increase in cognitive impairment as compared to younger patients. Therefore, the general human population increasing their life longevity leads to a greater chance of developing Parkinson’s Disease and the disease becoming more prominent. With these increased cases, it has been taken upon by scientists to research an approach to alleviate the symptoms of Parkinson’s³. Current interventions to alleviate the symptoms of Alzheimer’s include Carbidopa-levodopa, dopamine agonists, and MAO B inhibitors¹.

Parkinson’s at the Molecular Level

The essential cause of Parkinson’s Disease is the death of dopaminergic neurons – neurons responsible for synthesizing the dopamine neurotransmitter. Both enzymatic and non-enzymatic oxidation of dopamine generates oxygen species that are reactive, resulting in apoptotic cell death in dopamine neurons. Neurotoxins such as MPTP, TCE, and PERC also contribute to cell death^5.. This cell death occurs particularly in the substantia nigra, a location in the brain that is responsible for the production of dopamine. Because this dopaminergic neuron loss is what results in Parkinson’s, administration of the aforementioned medications such a Carbidopa-levodopa is an effective way to counter Parkinson’s symptoms since Carbidopa is a decarboxylase inhibitor that is able to prolong the life of levodopa – which converts to dopamine⁴. All prescribed medications are efforts to create more dopamine for the brain, but Deep Brain Stimulation seeks to circumvent the abnormal functions of the brain of a Parkinson’s patient by delivering electrical impulses inside the brain.

Deep Brain Stimulation

Deep Brain Stimulation, originating in the late 1980’s, is a revolutionary discovery that currently works as a treatment for movement disorders. Deep Brain Stimulation is an invasive procedure in which electrodes are implanted into certain areas of the brain, allowing for an electrical current to stimulate the brain. The intention of Deep Brain Stimulation is to interrupt the abnormal signaling that occurs in Parkinson’s patients, such as tremors, by sending an electrical impulse. The electrodes are specifically implanted in target areas of the basal ganglia – a subcortical nuclei primarily responsible for motor control – such as the subthalamic nucleus or globus pallidus internus. The subthalamic nucleus is in charge of motor regulation, while the globus pallidus internus is responsible for inhibiting the ventral lateral nucleus and ventral lateral nucleus of the thalamus. To elaborate, the function of this portion of the brain is regulation of motor movement, since the areas it inhibits are centers for motor control⁷. This is done to change the activity between the direct and indirect basal ganglia pathways to promote motor movement without the dopamine⁶.

Deep Brain Stimulation and the Direct Basal Ganglia Pathway

In the direct basal ganglia pathway, the glutamate neurons project from the thalamus to motor regions in the cerebral cortex. These excitatory projections stimulate movement and are regulated by the globus pallidus internus and substantia nigra pars reticulata. These regulations are known as inhibitory projections, which inhibit thalamic neurons and suppress movement. From the cerebral cortex, the stimulation continues to the striatum through the corticostriatal pathway, where neurons in the striatum are activated and release GABA to the globus pallidus internus and substantia nigra pars reticulata. This inhibits the inhibitory projections, allowing for thalamus signals to flow freely to the cerebral cortex. The substantia nigra pars compacta is believed to control the striatum by releasing dopamine, creating further movement⁸. Thus, with the electrical stimulation of the subthalamic nucleus or globus pallidus internus, motor function can be regulated since the electrodes will control the inhibitory projections and the excitatory projections within the direct basal ganglia pathway. As a result, the most prominent symptoms of Parkinson’s – tremors, rigid muscles, and others – are regulated through these electrode stimulations.

Here is a Youtube video that explains this concept more simply and provides diagrams.

2-Minute Neuroscience: Direct Pathway of the Basal Ganglia

Deep Brain Stimulation Compared to other Treatments

Deep Brain Stimulation only resolves motor issues within Parkinson’s patients and is not a cure to Parkinson’s. However, there are no treatments that are able to cure Parkinson’s, they only alleviate the symptoms that interfere with daily life. As mentioned before, the combined drug Carbidopa-levodopa is an effective treatment that works to prevent nausea. Other than this symptom relief, though, this medication is not enough to relieve the more pressing symptoms of Parkinson’s. There is a potential treatment that has been going through clinical trials, though. This method is a non-invasive ultrasound treatment that utilizes ultrasonic energy and is aimed at the globus pallidus. Rather than having to be put under anesthesia to have electrodes implanted in the brain, the patient is able to stay awake and alert throughout the treatment process. The patient is able to talk to the doctors and as a result, immediate adjustments could be made. After only a short time on this treatment, patients report their symptoms being relieved. Tremors, rigidity, and dyskinesia are all said to be greatly relieved from this novel treatment⁹. 

Final Thoughts

Deep Brain Stimulation has been an effective treatment throughout the decades, but the advent of more non-invasive methods, such as the ultrasound stimulation treatment, will be favored as more research is conducted and will likely take over Deep Brain Stimulation as a common treatment for Parkinson’s since the chances of complications occurring is much lower. In my own perspective, I believe that ultrasound stimulation is becoming an effective therapeutic treatment for a multitude of health issues. Having interned at a laboratory that explored sonogenetics – the non-invasive manipulation of neurons and other cells expressing exogenous protein channels – I had the opportunity to observe the process of stimulating cells with ultrasound and analyzing its effects firsthand. Utilizing ultrasound creates the potential to regulate systems that have become faulty or abnormal, such as the case with the direct basal ganglia pathway in Parkinson’s patients and the glucose regulation pathway in diabetic patients. 

Organizations and More

If you are interested in donating to organizations that provide relief to Parkinson’s patients, feel free to check out the links below.

If you want to navigate through other charities yourself and find the most reliable, Charity Navigator provides plentiful data for thousands of organizations.

Charity Navigator – Assessment of Charities 

Parkinson’s Foundation:

Parkinson’s Foundation – General Gift 

This Foundation has been rated as one of the most reliable charities. As seen on the website, your money contribution will be used to provide free educational materials, send out care kits, fund exercise classes, fund research, and more.

Parkinson’s Association:

Their mission is to “optimize quality of life for people affected by Parkinson’s disease through programs and services that enhance MIND, MOVEMENT, and MORALE.” This Association provides a variety of activities, programs, and opportunities for the community to help those with Parkinson’s. 

Parkinson’s Association – General Page 

Parkinson’s Association – General Information Brochure 

References

1. Mayo Foundation for Medical Education and Research. (2022, March 24). Parkinson’s Disease. Mayo Clinic. Retrieved April 20, 2022, from https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055 

2. Dorsey, E. R., Sherer, T., Okun, M. S., & Bloem, B. R. (2018). The emerging evidence of the parkinson pandemic. Journal of Parkinson’s disease. Retrieved April 20, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311367 

3.​​ Gilberto, L. (2007, September). The Relationship of Parkinson Disease with Aging. Jama Neurology. Retrieved April 20, 2022, from https://jamanetwork.com/journals/jamaneurology/fullarticle/794410#

4. U.S. National Library of Medicine. (2022). Levodopa and carbidopa: Medlineplus Drug Information. MedlinePlus. Retrieved April 20, 2022, from https://medlineplus.gov/druginfo/meds/a601068.html

5. Naoi, M., & Maruyama, W. (n.d.). Cell death of dopamine neurons in aging and Parkinson’s disease. Mechanisms of aging and development. Retrieved April 20, 2022, from https://pubmed.ncbi.nlm.nih.gov/10656535/ 

6. Sonne, J., Reddy, V., & Beato, M. R. (n.d.). Www.ncbi.nlm.nih.gov. Neuroanatomy, Substantia Nigra. Retrieved April 20, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK536995/ 

7.​​ Lanciego, J. L., Luquin, N., & Obeso, J. A. (2012, December 1). Functional neuroanatomy of the basal ganglia. Functional Neuroanatomy of the Basal Ganglia. Retrieved April 20, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543080/ 

8. Andrușca, Alexandru MD, P. D. (2022, March 13). Basal ganglia pathways. Kenhub. Retrieved April 21, 2022, from https://www.kenhub.com/en/library/anatomy/direct-and-indirect-pathways-of-the-basal-ganglia  

9. Kotz, D. (2022, March 2). A new era for parkinson’s disease treatment. A New Era for Parkinson’s Disease Treatment. Retrieved April 21, 2022, from https://www.umaryland.edu/news/archived-news/march-2022/a-new-era-for-parkinsons-disease-treatment.php