Topics and Speakers Lucien J. Côté, MD
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Synopsis
The basal ganglia only make up about 6 or 7% of the entire human brain; yet, damage to this system can have devastating results in exerting even the simplest of motor tasks. In this lecture, Dr Côté covers the anatomical features of this system, its function and biochemistry, and concludes with a discussion of Parkinson's disease, one of the diseases most commonly associated with damage to this system.
Historically, the basal ganglia were first called the extrapyramidal system by Dr Kinnear Wilson in the early twentieth century. He decided to divide the corticospinal system into the pyramidal system (a two-neuron system consisting of upper motor neurons in the primary motor cortex and lower motor neurons in the anterior horn of the spinal cord) and the extrapyramidal system or basal ganglia. The reason for this was because clinically, lesions in these two systems created different symptoms at the bedside. The pyramidal system controls all voluntary movements, while the extrapyramidal system (or basal ganglia) controls automated or involuntary movements, muscle tone, and posture.
Damage to the pyramidal tract causes paralysis while damage to the extrapyramidal tract causes rigidity. As Dr Côté points out, neurophysiologists today find this division somewhat arbitrary and misleading. The pyramidal and extrapyramidal systems are inextricably intertwined both functionally and anatomically,
What make up the basal ganglia and what are the system's functions? The basal ganglia are a group of six subcortical nuclei: the neostriatum (which includes the caudate and putamen); the paleostriatum (which includes the external globus pallidus (GPe) and the internal globus pallidus (GPi)); the subthalamic nucleus (STN); the substantia nigra (SN); the thalamus; and the red nucleus. Much of what is known about basal ganglia functions has come from studying the disorders associated with damage to it, such as chorea, athetosis, dystonia, and ballism. Studying these abnormalities of muscle movements has led scientists to conclude that the basal ganglia are in charge of three main tasks. First, they control the automatic execution of learned motor jobs, including preparation for and execution of cortically initiated movements. Secondly, they play a role in cognitive function, especially in spatial memory. Finally, they are in charge of coordinating simultaneous motor tasks. Dr Côté illustrates this last point by describing the difficulty that Parkinson's patient have with cutting a piece of meat. They struggle with this task because it involves coordinating two motor tasks: going back and forth with the knife plus applying the necessary pressure to cut the meat. The patient will slide back and forth with the knife, without applying pressure to the movement.
Biochemically, the basal ganglia produce GABA, norepinephrine, and dopamine. For the latter neurotransmitter, there are at least five dopamine receptors. An interesting fact is that the ability of the basal ganglia to produce dopamine is significantly reduced with age, which explains why Parkinson's disease mostly affects the elderly. Also, dopamine cells in the SN contain neuromelanin, a dark pigment, which gives the SN its characteristic dark color. Not much is known about the role of neuromelanin, but its accumulation with age has been associated with dopaminergic cell death or dopaminergic cell malfunction. It is the destruction of dopaminergic cells (and hence, the loss of neuromelanin) that is associated with Parkinson's disease.
Dr Côté concludes the lecture with a discussion of the symptoms of Parkinson's disease. Genetically, there are about ten abnormal genes associated with Parkinson's. Anatomically, the brain is afflicted with the aforementioned significant loss of pigment in the SN. Current research has pointed out that the changes in Parkinson's do not occur first in the SN, as was previously thought, but in the brainstem (i.e., the pigmented dorsal nucleus of the vagus) and then moves up to the SN from there. There is also a production of Lewy bodies. Lewy bodies are essentially abnormal protein aggregates that are produced within the dopamine cell when the chaperone complex does not fold certain proteins correctly. Eventually, the cell dies. Physically, Parkinson's patients cannot coordinate simultaneous motor tasks and are afflicted with a profound fatigue that is unresponsive to current medication. These physical symptoms are accompanied by psychiatric symptoms such as depression, trouble making decisions, and a tendency to be very quiet in social situations. Currently, no cure for Parkinson's disease exists at this time. Treatment with Sinemet (levodopa) can relieve some symptoms in its early stages. In the subsequent lecture of this course, Dr Seth Pullman describes treatments for Parkinson's in detail.
