1. Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4. Things we can do about it 5. Questions

2. Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4. Things we can do about it 5. Questions

3. Clinical Hallmarks of Tourette's Syndrome Jankovic J. N Engl J Med 2001;345:1184-1192 Tics: Motor Phonic Sensory TOURETTE SYNDROME

4. Temporal course of symptoms in TS Natural history of Tourette Syndrome Jankovic J. N Engl J Med 2001;345:1184-1192

5. Tourette’s Syndrome Premonitory Urge  Discomfort  Tic Repetitive Undesired/unwilled “Compelled”

6. Like a sneeze that keeps building or an itch that won’t go away… the tag on the back of your shirt collar... Leckman et al. 1993

7. Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4. Things we can do about it 5. Questions

8. The Big Picture

9. How the brain works

10. Some disorders characterized clinically by deficient inhibition (gating) of motor, sensory or cognitive information: Huntington’s Disease Tourette Syndrome Obsessive Compulsive Disorder Schizophrenia ……

11. HD Frey et al. Albin et al. TS Schwartz et al. OCD Csernansky et al. Lewis et al. Narr et al. SZ C S P T Mink 2006

12. Spiny I GABAergic neuron

13. Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4. Things we can do about it 5. Questions

14. Albin et al. 2003 CTL TS ∆ Elevated striatal levels of VMAT in TS

15. Findings from the TSA Neuroimaging Consortium shows that the ventral striatum are called the nucleus accumbens is significantly smaller in TS children than in age-matched control children

16. Bloch et al., 2005

17. Copyright ©2005 by the National Academy of Sciences Kalanithi, Paul S. A. et al. (2005) Proc. Natl. Acad. Sci. USA 102, 13307-13312 Increase in the number of PV-containing neurons in the GPi (and reduced numbers in striatum) of TS patients

18. TS: Postmortem Findings Two classes of interneurons are reduced in striatum (caudate and putamen), and perhaps increased in GPi: Reduced number of PV+ fast-spiking striatal GABAergic interneurons in the striatum (51% and 37% reductions in the caudate and putamen, respectively, and a 122% increase in the GPi (Kalanithi et al. 2005). 50-60% reduction in “tonically active” cholinergic interneurons in associative and sensorimotor (but not limbic) striatum (Kataoka et al. 2010). Striatum GPi Neuronal Migration “Bottleneck”?

19. Summary of main findings in brain studies of TS: Within different parts of the basal ganglia: 1.Excesses of chemicals related to the neurotransmitter, dopamine 2.Reduced size of specific areas 3.Smaller size predicts symptom persistence 4.Wrong proportions of certain neurons suggesting an interruption of cell migration early in development

20. TS runs in families

21. Leckman et al. Familial developmental pattern of tic severity

23. Leckman et al. 1993 Kataoka et al. 2010 Albin et al. 2003 Abelson et al. 2005

24. Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4. Things we can do about it 5. Questions

25. TREATMENT Easiest ways to correct abnormal neural circuit activity in brain disorders: 1. Change thoughts (psychoeducation, cognitive / psychotherapy, etc.) 2. Change behaviors (behavioral therapy (CBIT)) 3. Change chemicals (medication, nutrition, sleep, etc.) 4. Change electrical activity (neuromodulation)

26. Schwartz et al. 1996

27. Efficacy of Habit Reversal Therapy (HRT) in Adults with TS

28. TS Medication: General Classes 1.Anti-dopaminergic therapies Examples: haloperidol, pimozide, risperidone, tetrabenazine 2. Alpha-noradrenergic agonists Examples: clonidine, guanfacine 3. Medications used primarily for OCD symptoms Examples: fluoxetine, citalopram, sertraline 4. Medications used primarily for ADHD: Examples: amphetamine, methylphenidate, atomoxetine 5. Botulinum toxin

29. Deep Brain Stimulation (DBS) C S P T

30. http://www.youtube.com/watch?v=TyW6yJTBhlg Ackermans L et al. Brain 2011;134:832-844 Individual changes in total YGTSS scores in six patients with Tourette syndrome with thalamic DBS

31. The role of advocacy organizations in the application of new therapeutic technologies

32. What can I do? 1.Learn about TS! 2.Get active in the community (like this group)! 3.Stay connected to the TAA (www.tsa-usa.org) !www.tsa-usa.org 4.Participate in TS research studies !

33. Outline: 1. What is TS? 2. How does the brain work? 3. What does the brain do differently in TS? 4. Things we can do about it 5. Questions