Animal Research: Unlocking Medical Miracles
Deep Brain Stimulation Offers Parkinson’s Patients New Hope
Deep brain stimulation (DBS), built on decades of human and animal research, offers clear benefits to patients with Parkinson’s disease, a disorder of the brain’s neural circuits that play a role in the control of movement.
DBS involves implanting electrodes in the brain and “uses electrical stimulation to regulate electrical signals in neural circuits to and from identified areas in the brain to improve movement symptoms,” according to the National Institute of Neurological Disorders and Stroke.
Parkinson’s disease (PD) symptoms include tremor of the limbs, difficulty in initiating movements, slowness of movement, muscular rigidity and forward flexed posture. Symptoms differ across patients and over time for each person. The disease is progressive and affects over a million people in the U.S. and more than 10 million worldwide.
The following short history of PD medical treatments explains how scientists identified the most effective target locations for successful DBS stimulation in patients with PD.
Surgeon James Parkinson first characterized the disease in 1817 and referred to it as the “shaking palsy.” Basic understanding of what caused the disease was lacking well into the 1900s.
Among the first PD treatments in the 1930s to the 1950s was surgical lesioning, or permanently inactivating, brain regions. This was centered on a group of brain structures, referred to as the basal ganglia, that lie deep in the brain. The basal ganglia are components of circuits involving the cerebral cortex, brain stem and thalamus, which are involved in the control of movement and behavior (see Figure 1). However, surgical interventions’ success was limited because surgeons at that time did not know the exact region of the basal ganglia that controlled movement.
A landmark advance came in the 1960s, not from surgery but from a medication called L-dopa introduced following the discovery of dopamine in the basal ganglia and its depletion in PD. This drug, which replaced dopamine in the brain, dramatically reduced PD symptoms and largely ended the need for surgery except for patients with unresponsive tremor. However, continued use of L-dopa led to problems for many patients who developed involuntary movements and motor fluctuations due to an early wearing off of the treatment effect.
This research ended the early idea that there was a center of neurons that controlled functions such as movement. Instead, scientists found it was a series of groups of neurons that had highly specific connections between them.
It was changes in the activity of these neurons that played a role in the control of movements and the disorders of those movements. These connected groups of neurons are circuits, like a connected series of components on an electronic board. Repair of one of these boards requires finding and fixing failed components. In a similar fashion, scientists’ task was to identify the groups of neurons (the components) and determine the connections between them (the circuits) and how they are related to movement.
Today the medical community views many movement disorders as “circuit disorders,” resulting from abnormal circuit activity. Those in the field widely believe the major signs and symptoms of neurologic and psychiatric disorders result from disturbances of circuits.
Scientists mapped out and studied the neuronal circuits in the basal ganglia of monkeys over more than 40 years. The monkey brain has an anatomical structure similar to humans, making it one of the closest nonhuman animal models for understanding the human brain. A breakthrough in the early 1980s occurred with the development of a nonhuman primate model of PD producing similar neurological symptoms as humans with the disease.
Tests with monkeys helped explain how dysfunction of a specific neuronal circuit involving a portion of the basal ganglia, the subthalamic nucleus (STN), could cause PD symptoms. Lesioning the STN reduced symptoms in the monkey model of PD, thus, providing a highly effective novel target for surgery.
Surgical inactivation of the same area in human patients also reduced PD symptoms. However, persistent side effects sometimes followed, so surgeons used electrical stimulation in human patients to see if deep brain stimulation of the subthalamic nucleus would reduce PD symptoms. It did.
Watch: Comparison of Movement Without and With DBS
Patients who receive chronic DBS experience a significant decrease in PD symptoms for at least five years after DBS surgical intervention and reportedly have an increased quality of life compared to medical therapy. DBS is a life-altering treatment for many PD patients, and over 160,000 patients worldwide have used DBS for treatment of Parkinson’s and other diseases.
Watch: Changed Life of a Parkinson’s Patient With Pulse Generator Implants
DBS is effective for a variety of movement disorders, such as essential tremor. Continued research offers hope that more doors will open for improved minimally invasive surgical treatments for not only PD patients but for other neurodegenerative diseases and disorders as well.
This article is based on: Understanding Parkinson’s disease and deep brain stimulation: Role of monkey models. Jerrold L. Vitek and Luke A. Johnson. Proceedings of the National Academy of Science USA. 2019 Dec 26;116(52):26259-26265.
Scientific guidance of this article was provided by Robert H. Wurtz, PhD, distinguished investigator emeritus at the NIH’s National Eye Institute. Dr. Wurtz has served as president of the Society for Neuroscience and has been elected to the National Academy of Sciences, National Academy of Medicine, and American Academy of Arts and Sciences.
This article was vetted by Mahlon DeLong, MD, emeritus professor of neurology, Emory University. Dr. DeLong was awarded a Breakthrough Prize in Life Sciences and Lasker-DeBakey Clinical Medical Research Award in 2014.