The basal ganglia is a structure in the brain that contributes to the initiation of movement as well as the control of movement. Through intrinsic pathways it sends signals to the motor cortex to begin motor pathways. However, it controls movement by inhibiting certain muscles by suppressing output through the thalamus. Damage to the basal ganglia leads to a set of symptoms very different from symptoms that arise from damage to descending motor pathways. Two diseases are traced back to disrupted pathways within the basal ganglia, Parkinson’s disease and Huntington’s disease. Huntington’s disease is a hereditary disorder that leads to symptoms such as choreic movement (brief, purposeless and involuntary). The official cause is unknown, but it is hypothesized that the indirect pathway within the basal ganglia is disrupted because of a loss of striatal neurons.
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Functional Anatomy

The striatum consists of the putamen and the caudate. The caudate has a head, body and tail. The Corpus striatum is the caudate, putamen and the globus pallidus. The globus pallidus has an internal segment (GPi) and an external segment (GPe). The Lenticular nucleus consists of the caudate and the globus pallidus. Other parts of the BG include the subthalamic nucleus and the substantia nigra which consists of two parts: pars compacta (SNc) and pars reticulata (SNr).
Input:
The BG receives input from the cerebral cortex, the intralaminar nucleus of the thalamus and the substantia nigra compacta. Most of the information goes to the striatum. The projections are segregated based on the area it is sent from. The frontal lobe projects to the caudate head and putamen. The parietal and occipital lobe project to the caudate body. The temporal lobe projects to the caudate tail. The primary motor cortex and primary somatosensory cortex project to the putamen. The premotor cortex and supplementary motor cortex project to the caudate head.
Output:
The output structures in the basal ganglia are the GPi and the SNr. The GPi sends output to the thalamus with neurotransmitter GABA. It sends sensorimotor information and neocortical information. The SNr also uses GABA, but projects to the superior colliculus; this projection relays information about eye movement.
Pathways:
  • Direct pathway disinhibits the thalamus to excite the cortex for initiation of movement.
    • o The direct pathway begins with an excitatory signal from the sensorimotor cortex to the striatum with the neurotransmitter Glutamate. The striatum sends inhibitory signals through GABA and substance P to the SNr and GPi which then inhibits the thalamus or disinhibits the thalamus so that it can send excitatory glutamate to the cortex to allow for the initiation of movement.
    • The indirect pathway inhibits the thalamus therefore inhibiting the cortex to suppress unwanted movement during action.
      • o The indirect pathway also begins with glutamate projections from the cortex to the striatum. Inhibitory GABA is then projected to the GPe. The GPe sends GABA inhibitory signals to the subthalamic nucleus which then sends excitatory glutamate to the SNr and GPi. When the output structures are excited they send inhibitory GABA to the thalamus, but unlike the direct pathway this further inhibits the thalamus instead of dis-inhibiting it. With the thalamus having a stronger inhibition it sends GABA to the cortex therefore preventing movement from occurring.
      • Nigrostriatal projection excites the direct pathway while simultaneously inhibiting the indirect pathway. The outcome of this dual action is excitation of the cortex. This projection occurs with the release of dopamine from the SNc that affects the striatal neuron receptors differently. Striatal neurons are medium spiny neurons. There are D1 and D2 receptors in the striatum that react to the dopamine neurotransmitter differently. Dopamine excites D1 receptors therefore exciting the direct pathway. Dopamine inhibits D2 receptors therefore inhibiting the indirect pathway. Both of these responses lead to excitation of the cortex.
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Facts about Huntington’s disease
  • 4-8/100,000 people are diagnosed with HD
  • 25,000 cases in the US
  • 25% of people with HD have late onset (symptoms after 50 years old)
  • No cure

Huntington’s disease stems from a disruption in the balance of the direct and indirect pathways. Therefore actions such as random, involuntary movement occur; these are known as choreic movement. Choreiform movements can be continuous, but uncontrolled and occur specifically in the extremities and the face. They also occur without behavior significance. Other symptoms include:
  • Inability to maintain tongue protrusion or hand grip.
  • Initially muscle tone is unaffected, but rigidity will become part of the disease.
  • Eye movement abnormalities
    • o Saccadic movement is disrupted
    • o Decrease in velocity of movement
    • o Undershooting of a target
    • o Latency in initiation of movement
    • o Gaze fixation abnormalities
    • o Interrupted smooth pursuit of eyes
    • o Inability to suppress reflex saccades to a visual stimulus
Pathology
The official cause of HD is unknown. However, there are observed effects that have been seen in patients with HD. There is atrophy of the striatum in the basal ganglia and loss of small and medium striatal neurons. Atrophy of the putamen is connected to the neurologic symptoms as well. There is white matter degeneration in the frontal cortex. There is a decrease in production of glial cells that inhibit neural transmission and lead to cortex and cerebellar changes. In the early and middle stages of the disease the neurons projecting from the striatum to the subthalamic nucleus are depleted therefore a reduction of GABA, Ach and metenkephalin. Therefore there are higher concentrations of dopamine and norepinephrine. The balance of inhibition and excitation response in the thalamus is disrupted because the balance of the indirect and direct pathway is off. There is excessive excitation of the thalamocortical pathway which leads to excessive abnormal involuntary movements. The neurons fire randomly and inappropriately which causes the motor cortex to execute motor programs with no conscious control. The later stages involve loss of direct inhibitory substance that causes more inhibition of the thalmocortical output. It also leads to rigidity and bradykinesia.
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There is no cure for HD, but there is treatment to help symptoms and for people to learn to live with the disease. There is psychological therapy for both patients with HD and their families. It can be a difficult change to someone’s lifestyle; many support groups have been created for people to learn to accept the change. Medical treatment involves anticonvulsant drugs to relieve chorea symptoms. There are also antipsychotic agents that block dopamine neurotransmission to help reduce the amount of excitation to the motor cortex. Surgical procedures are also available, but not highly responsive. The internal globus pallidus can be removed or adrenal medullary grafts can be implanted into the brain.

Summary
HD is a hereditary disease that stems from disruptions in the basal ganglia. There are two pathways within the basal ganglia: the direct and the indirect pathways. The direct pathway sends signals to the motor cortex to initiate movement and the indirect pathway sends inhibitory signals to the motor cortex to prevent movement at rest or control certain muscles during specific movements. When the striatal neurons are depleted within the basal ganglia both pathways are disrupted and the direct pathway is favorited leading to uncontrolled choreic movement. Although the official cause of HD is unknown, there have been many attributes of the basal ganglia that are reoccurring in patients. Through brain images it is clear that the striatal neurons deplete over time in HD patients. The biggest treatment is therapy (both physical and psychological) to learn to live with the changes in movement.
Vocabulary
  • Ach- inhibitory neurotransmitter
  • Atrophy- decrease in size or wasting away
  • Bradykinesia- slow movement
  • Caudate – anatomical structure of basal ganglia, specifically the striatum
  • Choreic movement- brief, involuntary movement
  • Descending motor pathway- information is sent from higher brain centers through the spinal cord to the muscles
  • Dopamine- neurotransmitter that is part of nigrostriatal pathway, sent from SNc to striatum
  • GABA- inhibitory neurotransmitter
  • Glial cells- cells that inhibit neural transmission and are found in the cortex and cerebellum
  • Globus pallidus- anatomical structure in the basal ganglia that consists of an internal and external component, it is also part of the Corpus striatum
  • Glutamate- an excitatory neurotransmitter
  • Intrinsic pathways- projections of neurotransmitters within the basal ganglia
  • Metenkephalin- inhibitory neurotransmitter
  • Motor cortex- part of the cerebral cortex in brain where intentional movement in initiated, sends input to basal ganglia
  • Nigrostriatal projections- when dopamine is released from SNc to striatum
  • Putamen- anatomical structure of basal ganglia and part of striatum
  • Saccadic movement- rapid movement of the eye
  • Somatosensory cortex- part of cerebral cortex in brain that receives sensory information and sends input to the basal ganglia
  • Striatal neurons- neurons in the striatum
  • Striatum- anatomical structure of the basal ganglia composed of the putamen and caudate.
  • Substance P- inhibitory neurotransmitter
  • Substantia nigra- anatomical structure of the basal ganglia consisting of two parts, reticula which sends output from basal ganglia and compacta which sends input to the basal ganglia.
  • Subthalamic nucleus- anatomical structure of basal ganglia important in the indirect pathway
  • Superior colliculus- receives output information from the basal ganglia
  • Thalamus- receives output information from the basal ganglia and projects to the cortex.
Quiz
  1. 1. The GPi and GPe send output from the basal ganglia. (T/F)
  2. 2. GABA is the main inhibitory neurotransmitter. (T/F)
  3. 3. The direct pathway initiates movement because the thalamus is excited. (T/F)
  4. 4. Which of the following is not a symptom of HD?
    1. a. Choreic movement
    2. b. Random movement
    3. c. Tremors/shaking
    4. d. Disrupted saccadic movement
    5. 5. What neurotransmitter has a higher concentration with HD?
      1. a. Ach
      2. b. Dopamine
      3. c. GABA
      4. d. Metakephaline
      5. 6. With part of the basal ganglia is atrophied with HD?
        1. a. Subthalamic nucleus
        2. b. Substantia nigra
        3. c. Globus pallidus
        4. d. Striatum
        5. 7. Match the following area of the brain to the part of the basal ganglia it innervates:
          1. a. Frontal lobe
          2. b. Parietal/occipital lobe
          3. c. Temporal lobe
i. Caudate body
ii. Putamen
iii. Caudate tail
  1. 8. Draw the direct pathway of the basal ganglia.
  2. 9. Draw the indirect pathway of the basal ganglia.
  3. 10. Describe how the balance of the pathways is disrupted in patients who have HD.
Answers: F, T, F, C, B, D, a-ii, b-i, c-iii



Further Reading
http://neuroscience.uth.tmc.edu/s3/chapter04.html: overview of the basal ganglia and brief description of HD
Progenitor Cells and Adult Neurogenesis in Neurodegenerative Diseases and Injuries of the Basal Ganglia:http://web.ebscohost.com/ehost/detail?vid=3&hid=122&sid=d3374831-c0a5-4b73a03f1ce3a5747b99%40sessionmgr114&bdata=JkF1dGhUeXBlPWlwJnNpdGU9ZWhvc3QtbGl2ZSZzY29wZT1zaXRl#db=aph&AN=24488333: the response of the forebrain to the degeneration of the striatum in the basal ganglia and how it affects HD.
Impact of Huntington's across the entire disease spectrum: the phases and stages of disease from the patient perspective.: http://web.ebscohost.com/ehost/detail?vid=4&hid=122&sid=d3374831-c0a54b73a03f1ce3a5747b99%40sessionmgr114&bdata=JkF1dGhUeXBlPWlwJnNpdGU9ZWhvc3QtbGl2ZSZzY29wZT1zaXRl#db=aph&AN=64122733: An article based on interviews with HD patients and how the disease has effected everyday life physically, emotionally and socially.
Variation within the Huntington'sDisease Gene Influences Normal Brain Structure. http://web.ebscohost.com/ehost/detail?vid=4&hid=122&sid=d3374831-c0a5-4b73-a03f-1ce3a5747b99%40sessionmgr114&bdata=JkF1dGhUeXBlPWlwJnNpdGU9ZWhvc3QtbGl2ZSZzY29wZT1zaXRl#db=aph&AN=79911123. This article discusses how the genetic make-up of HD affects the brain structure and how it compares to normal brain structure.
Picture References (in order that they appear)
http://www.macalester.edu/academics/psychology/whathap/ubnrp/dopahypoweb04/josh%20page%202.html
http://speakcampaigns.org/sitepages.php?a=24
http://radiology.rsna.org/content/early/2011/05/25/radiol.11101918/F1.expansion.html
http://missinglink.ucsf.edu/lm/ids_104_neurodegenerative/case2/BGPop.htm
https://www.stanford.edu/group/hopes/cgi-bin/wordpress/2010/06/the-basic-neurobiology-of-huntingtons-disease-text-and-audio/
Book Sources
Goodman, Catherine C., MBA, PT, Kenda S. Fuller, PT, NCS, and William G. Boissonnault, MS, PT. Pathology Implications for the Physical Therapist. Second Edition ed. Philadelphia: Saunders, 2003. Print.
"Basal Ganglia (Section 3, Chapter 4) " Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston. The University of Texas Health Science Center at Houston (UTHealth)., 1997. Web. 03 Dec. 2012. <http://neuroscience.uth.tmc.edu/s3/chapter04.html>.