Cognitive Challenge Summary

1. Cognitive Challenge Summary • Analysis of Phase II data • 240 sessions analyzed using BPutil pipeline, BIRN QA and Eventstats • ROI analysis of MFG, IPL, and STG • Comparison of FIPS and BPutil for Iowa data • New task development • Emotional oddball (event-related) • Emotional executive (blocked) • Movie clips

2. 15s .5s 6-15 s 6-15 s … … … 1000Hz 1200Hz Constant Fixation

3. Controls: N=41, p<1x10-10 Patients: N=44, p<1x10-5 MFG, Right Hemisphere, Visit 1 Visit 1 Controls Patients Slice Depth: Z=-11 Visit 2 MFG, Right Hemisphere, Visit 2

5. Voxel Counts by Visit and ROI

6. Time-Course by Visit and Diagnosis in MFG

7. Auditory Oddball

8. Auditory Oddball Summary • Robust activations of dlPFC, IPL, STG, insula, cingulate, thalamus, and motor cortex • In all locations, controls > patients • Strong visual cortex activation suggests that infrequent tones evoke an orienting response • Brainstem activation is also suggestive, but less visible in count conditions

9. Prompt Encoding Probes (14 Total) 0 2 1 389 7 2 4 . . . Learn 5 items 7 * 5 * 44 6 5 1 . . . Learn 3 items * * 9 * * 3 9 2 8 . . . 1 item Learn … … … … 0s 2s 4s 6s 8s 10s 46s 4s-20s Fixation 4s-20s Fixation

10. IPS SIRP

11. MFG SIRP

12. Preliminary SIRP Summary • Strong co-activation of regions also activated by Auditory Oddball (except STG) • At low and medium load, patients > controls during probe intervals • At high load, patients ~= controls

13. MFG

14. IFG

15. STG

16. IPS Encode

17. IPS Probe

18. MFG Encode

19. MFG Probe

20. Cognitive Challenge Summary New task development • Emotional oddball (event-related) • Emotional executive (blocked) • Movie clips

22. Emotional Distracter Task Standard Targets Novels Neutral Emotional 84% 8% 4% 4%

23. ... ... ... ... ... Emotional Distracter Task Yamasaki, LaBar, McCarthy, PNAS, 2002

24. Sad Stimulus Distracter Task Wang, LaBar, McCarthy, Biol Psychiat, in press

25. Emotional Distracter

26. Emotional Distractor TaskMiddle Frontal Gyrus (anterior)

27. Emotional Distractor TaskAmygdala

28. Emotional Distracter

29. Anterior MFG Posterior IFG Emotional Distracter Task

30. Emotional Distracters and Working Memory Phase II Phase I (14s) (15s) Novel stimuli (6s) + + + 3.5s 1.5s Memoranda Probe Dolcos and McCarthy, J Neurosci, 2006

31. dlPFC MR signal change (%) Corrected Recognition Scores AMY MR signal change (%) Scrambled Scene Distracters Neutral Scene Distracters Emotional Scene Distracters Increased distractibility to emotional distracters linked to differential patterns of activity in the dorsalexecutive vs. ventralaffective neural systems.

32. Amygdala activity to emotional distracters MR signal change (%) 5.5 6.75 8 time (sec)

33. Negative Distracter Neutral Distracter Meaningless Distracter

34. Emotional Oddball • Ayse Belger’s group collected data • 10 CONTROLS, 11 SCZ PATIENTS

35. MFG SCZ PATIENTS CONTROLS

36. Ifg/BA 47 SCZ PATIENTS CONTROLS

37. OF SCZ PATIENTS CONTROLS

38. FFG SCZ PATIENTS CONTROLS

39. Posterior Parietal SCZ PATIENTS CONTROLS

40. AMYGDALA SCZ PATIENTS CONTROLS

44. Emotional Executive Task, Block-Design Executive Block Neutral Block Emotional Block … … … … … … Scrambled Images … … Fixation … 80s 30s 40s 70s 50s 0s 60s 20s 10s

45. Blocked Emotional Executive MFG IFG vmPFC

46. Left MFG

47. Left IFG

48. Inferior Frontal Gyri

49. vmPFC

50. vmPFC