What is Tourette’s syndrome?

It states in the DSM-5 that the syndrome is diagnosed when the individual has presented multiple motor and one or more vocal tics for at least a year. The disorder must present itself before the age of eighteen in order to be diagnosed as Tourette’s syndrome. In order to be considered a tic due to Tourette’s syndrome, the tic cannot be a side affect of substance abuse or another medical condition. [1] Tics due to the syndrome tend to affect the face, neck, shoulders, and voice. [3] Breakthroughs and new insights into the neural circuits and structures of the brain, specifically the basal ganglia, have made it possible for doctors and researchers a like to have a better understanding of the neurophysiological causes of Tourette’s syndrome.

Key Terms

Caudate – Part of the striatum, receives input from the cortex and projects to the globus pallidus.
CSTC pathways - Abbreviation for cortico-striato-thalamo-cortical pathway, the direct and indirect pathways fall within this category
Direct Pathway – Pathway within the basal ganglia which facilitates movement through the release of neurons from tonic inhibition
Globus Pallidus (external segment) – Part of the indirect pathway
Globus Pallidus (internal segment) – Part of the direct pathway
Indirect Pathway – Pathway within the basal ganglia, which modulates the direct pathway
Midline Nuclei of the thalamus – Projects through out the cerebral cortex [7]
Premotor Cortex – The part of the brain that influences motor behavior through its connections within the primary motor cortex. It also has axons that project into corticospinal pathways and influences the motor neurons of the brainstem and spinal cord. [6]
Primary Motor Cortex – Found in the precentral gyrus of the cerebral cortex, necessary for voluntary movement. Receives input from basal ganglia, and the cerebellum from pathways through the thalamus, as well as somatosensory input [6]
Somatosensory Cortex – Processes sensory information received from the sensory receptors of the body (i.e. joint receptors, subcutaneous receptors, etc) [6]
Putamen – Part of the striatum, receives input from the cortex and projects to the globus pallidus
Sensori-motor cortex – Consist of the Primary Motor and Primary somatosensory cortex
Striatum – Sometimes referred to as the neostriatum, contains the caudate and the putamen.
Substantia nigra pars compacta – contains dopaminergic synapses that project to the caudate and putamen to excite/inhibit depending on the receptors.
Substantia nigra pars reticulata – Sends output from the basal ganglia to the thalamus [6]
Supplementary motor area – Aids in the control of complex movement [4]
Thalamus – Modulates sensory input, relays information from the cerebellum and the basal ganglia to the cortex [7]
Tic – a sudden, rapid, recurrent, non-rhythmic motor movement or vocalization. [1]
VA/VL complex – Combination of the ventral anterior and ventral lateral nuclei of the thalamus, gives feedback to basal ganglia output

Functional Anatomy

Basal Ganglia


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The Basal Ganglia is divided into five functional parts: The striatum, pallidum, thalamus, substhalamic nucleus, and the substantia nigra [Figure 1]. The striatum is the area of the basal ganglia that receives the input. The information coming into the striatum comes from all areas of cerebral cortex and parts of the thalamus. The striatum can be further broken down into two parts: the caudate and the putamen. The caudate tends to receive input from the frontal, parietal, temporal, and occipital lobes as well as the premotor cortex and supplementary motor areas. The putamen receives input from the primary motor and primary somatosensory cortex. The medium spiny neurons of the caudate and putamen then project to the internal segment of the globus pallidus [Figure 2a]. The spiny neurons have an inhibitory affect on the tonically active inhibitory neurons in the internal segment of the globus pallidus [Figure 2a]. [6] These neurons then project into the VA/VL complex of the thalamus. The substantia nigra pars compacta has an excitatory affect on the caudate/putamen through the release of dopamine to the D1 receptors of the caudate and putamen. [4,6]
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The “direct pathway” [Figure 3a] of the basal ganglia acts to release the motor neurons from tonic inhibition. In the “indirect patheway”, the medium spiny neurons project to the external segment of the globus pallidus. The “indirect pathway” [Figure 3b], on the other hand, serves to increase tonic inhibition. The neurons from the external segment of the globus pallidus then project to the subthalamic nuceleus. The subthalamic nucleus, receiving both excitatory input from the cortex and inhibitory input from the external segment of the globus pallidus, then projects to the internal segment of the globus pallidus, which in turn makes any changes that need to be made to the “direct pathway”. [6]

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Tourette’s and the CSTC pathways

The CSTC pathways are the pathways that project information from certain areas of the cortex, through the striatum, and after traveling through the globus pallidus reaches the VA/VL complex of the thalamus. From there, information is projected back to the cortex. These pathways, both direct and indirect as discussed in the previous section, help elicit and modulate movement. The pathophysiology of Tourette’s syndrome can be traced to the sensorimotor CTSC circuits. As discussed before, these pathways project from the sensori-motor, primary motor, and supplementary motor areasto the matrisomal portions of the putamen and the head of the caudate nucleus. [2] These sites then project to parts of the globus pallidus and the pars reticulata of the substantia nigra. From there, the information travels from the basal ganglia to the ventral-lateral and midline nuclei of the thalamus, and from the thalamus information is projected back to the cortex. Researchers believe that the development and function of these pathways play an important role in the initiation and performance of tics and compulsions. [2] One way researcher’s have begun to look at Tourette’s syndrome is as a syndrome in which major CTSC loops have been disinhibited. [2] In one study, researchers found that Tourette’s syndrome can be attributed to the combination of excessive motor pathway activity and reduced control of the CSTC circuit. [3] Studies have also shown that the release of glutamate in both the internal and external segments of the globus pallidus as well as the substantia nigra are different in people who have Tourrette’s syndrome as opposed to those who do not. [2]

Treatment

Being that Tourette Syndrome is a complex disorder that has both psychological and physiological base, there is no cure. Still, for many people the disorder can make day-to-day life difficult due to the constant disruptions. People affected by the order may seek pharmaceutical intervention. Dopamine agonists have been tested and proven to have an inhibitory affect on tics. [2] It’s important to note that medication can only cure the symptoms, not the disorder itself. Medication is usually employed if a specific tic can be significantly reduced. Treatments that focus on the behavioral aspect of the syndrome have become more popular and well accepted. Comprehensive Behavioral Intervention for Tics (CBIT) aims to focus on reversing the habits of the patient that seem to been tic inducing. Strategies like discussing what situations seem to be more tic inducing than others, are employed by the therapist in the hopes to help lessen the severity of the tic. [8]




Summary

As research has found, the basal ganglia play an important role in the facilitation of wanted movement and the inhibition of unwanted movement. It comes as no surprise that breakthroughs in research about Tourette’s syndrome can be attributed to the dysfunction of the basal ganglia. Tics arise due to the inability of the direct and indirect pathways to inhibit unwanted movement. Medications have been found to be affective in treating the symptoms of Tourette's Syndrome, but behavioral therapy has been found to be most affective form of treatment.


Suggested Readings and Websites:

https://www.tourette.org/about-tourette/overview/what-is-tourette/
This website gives a helpful overview of how Tourette’s Syndrome manifests itself, prevalence, causes, and conditions that also tend to occur along with it.

http://www.tourettesyndrome.net/
This website provides resources and helpful articles to parents with school-age children dealing with Tourette’s syndrome.

Passing for Normal: A Memoir of Compulsion by Amy S. Wilensky
This book offers the reader the perspective of what it’s like to live with a commonly misunderstood disorder.

Tourette's syndrome--tics, obsessions, compulsions : developmental psychopathology and clinical care by James F. Leckman
This book offers a variety of articles covering both the physiological and psychological aspects of Tourette’s syndrome and ways to treat it.

Content Quiz


1.) The CTSC pathway is the:
a.) cortico-striato-thyro-cortical pathway
b.) cortico-striato-thalamo-cortical pathway
c.) cerebro-striato-thyro-cortical pathway
d.) cerebro-striato-thalamo-cortical pathway

2.) The basal ganglia consists of the striatum, the subthalamic nucleus, and the substantia nigra:
a.) True
b.) False

3.) The basal ganglia deals primarily with repetitive motor planning:
a.) True
b.) False

4.) The cortex has an excitatory affect on the external segment of the globus pallidus.
a.) True
b.) False

5.) Tourette’s syndrome is caused by two separate factors: either excessive motor pathway activity or reduced control within the CSTC pathways.
a.) True
b.) False

6.) The external segment of the globus pallidus:
a.) plays a role in the indirect pathway
b.) plays a role in the direct pathway
c.) has an inhibitory affect to the subthalamic nucleus
d.) sends excitatory input on the subthalamic nucleus
e.) A&C
f.) A&D
g.) B&C
h.) B&D

Essay: You have a patient who comes in exhibiting three different motor tics and two vocal tics, with only one motor tic and one vocal tic persisting for over a year. At this stage, can you definitively diagnose the patient with Tourette’s syndrome? Explain what is going on in neurologically within the patient that would cause them to have these involuntary movements.


Answers:
1.) B
2.) B: The striatum only includes the
3.) B: the basal ganglia is also included in the regulation of emotions
4.) A
5.) B: Research has found that Tourette’s syndrome is caused by a combination of the two factors.
6.) E

Media Sources

Figure 1
http://www.slideshare.net/danielveladuartemd/anatomy-of-basal-ganglia-13346638
Figure 2
https://www.ncbi.nlm.nih.gov/books/NBK10988/figure/A1226/?report=objectonly
Figure 3
https://www.ncbi.nlm.nih.gov/books/NBK10847/figure/A1252/?report=objectonly
Video 1

<iframe width="560" height="315" src="https://www.youtube.com/embed/jYRa-fpNonY" frameborder="0" allowfullscreen></iframe>

References

1. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Arlington, VA: American Psychiatric Association, 2013. Print.
2. Leckman, J.F. & Cohen, D.J. (1999). Tourette’s Syndrome: Tics, Obsessions, Compulsions. New York, NY: John Wiley & Sons, Inc.
3. Wang Z., Maia T. V., Marsh R., Colibazzi T., Gerber A., Peterson B. S. (2011). The neural circuits that generate tics in Tourette’s syndrome. Am. J. Psychiatry 168 1326–1337. 10.1176/appi.ajp.2011.09111692
4. Byrne, J. H. and Dafny, N. (eds.), Neuroscience Online: An Electronic Textbook for the Neurosciences
http://nba.uth.tmc.edu/neuroscience/
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston (UTHealth)
© 1997, all rights reserved.
5.Ji G-J, Liao W, Yu Y, Miao H-H, Feng Y-X, Wang K, Feng J-H and Zang Y-F (2016) Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity. Front. Neuroanat. 10:93. doi: 10.3389/fnana.2016.00093
6. Purves D, Augustine GJ, Fitzpatrick D, et al., Neuroscience. 2nd ed. Sunderland, MA: Sinauer Associates; 2001.
7. Rand Swenson, DC, MD, PhD, Review of Clinical and Functional Neuroscience. https://www.dartmouth.edu/~rswenson/NeuroSci/chapter_10.html.
Dartmouth Medical School
© Swenson 2006
8. Tourette’s Syndrome.
https://www.cdc.gov/ncbddd/tourette/treatments.html
Center for Disease Control and Prevention