Motor Systems

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Motor Systems

• The Basal Ganglia
• Tourettes syndrome

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To move is all that mankind can do..for such the
sole execution is muscle, whether in whispering a
syllable or in felling a forest.

• Charles Sherrington, 1924

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Basal GangliaExtrapyramidal Motor system

• Caudate
• Putamen
• Globus pallidus
• Subthalamus
• Substantia Nigra
• Modulation of motor control
• Modulation of cognitive control

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      FIGURE 1 Location of basal ganglia in the
human brain. (A) Coronal section. (B)
Parasagittal section.
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Brain circuits
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Basal Ganglia- cortical loops

• Direct pathway Excite cortex
• Indirect pathway Inhibit cortex

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Basal Ganglia- Thalamic- Cortical- Loops
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Two hypothesis regarding the direct and indirect
pathways

• 1) Direct activates the desired motor program
  whereas the indirect inhibits unwanted motor
  programs
• 2) The direct and indirect act on the same motor
  program, allowing for greater control of movement

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Dopamine modulates the basal ganglia

• Dopamine excites the direct pathway (via D1
  receptors)
• Dopamine inhibits the indirect pathway (via D2
  receptors)

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Consider what happens if there is an imbalance in
direct/indirect pathway activation

• Overactivation of the direct pathway, or
  underactivation of the indirect pathway leads to
  excessive movements, or undesired movements
• Overactivation of the indirect pathway or
  underactivation of the direct pathway leads to a
  poverty of movement

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Tourettes syndrome

• Motor tics
• Simple
• complex
• Vocal tics
• Simple
• complex

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• When I was nine-years old, an imp took up
  residence in me. One afternoon he prodded the
  left side of my face from the inside, causing my
  lips to purse and curl askew toward my squinting
  left eye. Without yet knowing why, I rapidly
  blinked and shrugged. I grunted. I threw back
  my head and squeaked while my fists smacked my
  bruised abdomen.

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Tourettes syndrome

• First published account 1825 Jean-Mark Itard
• 1885 George Albert Edward Brutus Gilles de la
  Tourette
• Estimated 100,000 Americans with TS
• Occurs 3-4 times more in males than females.
• Onset usually in late childhood
• Increased incidence of ADHD and OCD

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Pathophysiology

• Imaging studies
• Reduction in volume and other abnormalities in
  basal ganglia
• Alterations in brain activity

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Disruptions in habit formation
Marsh et al., 2004
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Treatment

• Haloperidol, DA antagonists (particularly D2
  antagonists)
• Amphetamine can trigger tics
• This is problematic for individuals with both
  ADHD and Tourettes syndrome
• SSRIs, serotonin also modulates the activity of
  the basal ganglia

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Dopaminergic Dysfunction

• Increase in dopaminergic activation
• IMBALANCE TOO MUCH ACTIVATION OF DIRECT COMPARED
  TO INDIRECT

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Increased Dopa uptake in left caudate
(adolescents)
Ernst et al., 1999
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Ernst et al., 1999
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Increased DA transporter binding
Müller-Vahl, et al., 2000
But findings have been inconsistent.
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Increased DA terminals in ventral striatum
Albin et al., 2003
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Dopaminergic dysfunction Increased dopamine
release
Singer et al 2002
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Singer et al 2002
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Increased DA transporters in drug-naïve TS
children
Cheon et al., 2004
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Increased striatal D2 receptors
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Summary

• Tourettes syndrome involves pathology of the
  basal ganglia
• May be related to dopaminergic dysfunction
• Ultimately, there is an imbalance of direct and
  indirect pathway activation