2. SynesthesiaSynesthesia Your brain and Steffie Tomson, Ph.D. UCLA Geffen School of Medicine steffietomson@gmail.com

3. The Brain

4. Brains have many distinct regions & functions

5. Neurons communicate via synapse

6. How do brain regions communicate?

7. Balint’s Syndrome

8. LINE LINELINE

9. synesthesiasynesthesia j v b e q t s u f a c m 7 3 713…

10. How do we study synesthesia? C Primate? No way to verify syn Mouse? No color vision

11. Humans: functional MRI (fMRI)

12. fMRI signal Source: Arthurs & Boniface, 2002, Trends in Neurosciences “713”

13. fMRI localizes brain regions How do synesthetes process graphemes? Controls Synesthetes VO2, VO1, V4, Brewer et al. 2005

14. In a second experiment, we show movies… Realistic grapheme presentation Achromatic children ’ s television How are color and grapheme regions related?

15. 713… Humans: functional MRI (fMRI)

16. Synesthetes cluster visual regions during SS audio Tomson et al. 2013 Audio Anterior RightLeft

17. Synesthetes cluster grapheme and color regions during SS audio Audio Anterior RightLeft Tomson et al. 2013

18. Neuroimaging Summary Grapheme and color regions are hyper-connected Synesthetes cluster visual regions Grapheme and color regions are more clustered in synesthetes than controls Take-home: There IS more communication between brain regions in synesthesia. The question now is how MUCH more is necessary for the percept?

19. Genetics of synesthesia Synesthesia Battery for remote phenotyping Oragene saliva kids 6,090 SNP Ilumina Linkage 12 Chip Tomson et al. 2011 Family linkage CS Synesthete Unaffected

20. Verify synesthesia Eagleman et al. 2007 with synesthete.org Consistency Results 5 Timed Congruency Test Consistency Test 5

21. Synesthesia genetics Family linkage study – 23 MB region chromosome 16 – Heterogeneous Whole exome sequencing – Non-coding Whole genome sequencing – Copy number variant – Epigenetic Twin studies Autosomal dominant incomplete penetrance

22. Synesthesia Summary Colored sequence synesthesia is linked to chromosome 16 Synesthetes connect grapheme and color regions more than controls Synesthetes cluster visual regions during audio stimulation Take-home: There IS more communication between brain regions in synesthesia. The question now is how MUCH more is necessary for the percept? What is the genetic mechanism?

23. Why is this important? When brain regions fail to communicate, you get disorders such as Alzheimer’s, Balint’s Syndrome, Autism Spectrum Disorder, and many others. Understanding these complex disease states starts with understanding the basic science behind global brain communication. Synesthesia is one way to answer these questions.

24. steffietomson@gmail.com

25. Function

26. When Things Go Wrong

27. Genetics of synesthesia Whole exome sequencing

28. Brain Cells Purkinje CellMossy Fibers

30. Hotspot on chromosome 16 between 52 – 76 MBP Family linkage analysis Tomson et al. 2011

31. Synesthetic activity bleeds into color areas The synesthetic brain How do synesthetes process graphemes? > Controls Synesthetes VO2, VO1, V4, Brewer et al. 2005

32. Functional Connectivity R=.88 R=.23 Brain region 1 Brain region 2 Brain region 3 Brain region 4 Time  Activity