Deep in the gray matter of the brain are the basal ganglia. The basal ganglia, along with the cerebral cortex and diencephalon, compose the region of the brain called the forebrain. The basal ganglia connect to the cortex and thalamus and organize muscle-driven “motor” movements of the body. They are the parts of the brain most affected by HD and many of the symptoms of HD result from damage to them.
The major divisions of the basal ganglia are the caudate nucleus, putamen, globus pallidus and substantia nigra.
The caudate nucleus is a collection of neuronal bodies that connects to many parts of the brain. Together with the putamen, it comprises the neostriatum. Its neurons are most affected by HD, and the deterioration of its connections result in behavioral changes and the inability to control emotions, impulses, thoughts or movements. Damage to the caudate may also result in the inability to experience intense feelings of embarrassment, guilt or shame. Individuals with caudate damage may become “stuck” on one idea or activity, resulting in a lack of self-awareness and inability evaluate their own behavior. This decreased self-awareness may cause individuals to be unaware of mistakes that are evident to others. It may also impair their ability to experience a range of subtle emotions and see other points of view, making social and personal relationships more difficult.
The caudate organizes and filters information that is sent to the frontal lobe, particularly information from the limbic system. Caudate malfunction can affect the functioning of the frontal lobes through a lack of information or an improper amount of information. The caudate assists the frontal lobes in prioritizing the transfer of information to other parts of the brain. Damage to the caudate makes it difficult for people with HD to prioritize tasks and organize their day, as well as to handle many simultaneous stimuli. Along with the putamen, the caudate also controls voluntary movement.
The putamen and caudate are collectively known as the neostriatum. Together, they control voluntary movement. The cells of the neostriatum are the first to die as a result of HD, disrupting both the indirect and direct pathways controlling movement. The death of neostriatal neurons in the direct motor pathway leads to the under-stimulation of the motor cortex, causing the slow speed of motor movement often seen in persons with HD. The death of neostriatal neurons in the indirect motor pathway leads to over-stimulation and chorea.
(For more information about these motor pathways, click here.)
Neostriatum / Striatum
The neostriatum, comprised of the caudate and putamen, transmits information to the subthalamic nuclei that modulate motor control. Together, the neostriatum and globus pallidus make up the striatum.
The globus pallidus relays information from the caudate and putamen to the thalamus and is part of the striatum. In HD, both its external and internal regions suffer neuronal loss. Gliosis, the excessive growth of cells that normally support and protect neurons in the globus pallidus, is implicated in juvenile HD. Individuals who experience rigidity rather than chorea may also have damage to the globus pallidus.
The substantia nigra is generally considered part of the basal ganglia due to its similar neuronal structure and related function of motor control, but may also be considered part of the midbrain due to its location. It contains most of the neurotransmitter dopamine in the brain and also participates in motor coordination.