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. Constant Fixation 15s ……….5s6-15 s 1000Hz1200Hz

3. Slice Depth: Z=-11 Controls Patients Controls: N=41, p<1x10 -10 Patients: N=44, p<1x10 -5 Visit 1 Visit 2 MFG, Right Hemisphere, Visit 1 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. Learn Probes (14 Total) 0 2 1 3 8 9 7 2 4... 7 * 5 * 4 4 6 5 1... * * 9 * * 3 9 2 8... Prompt Learn … Encoding … 4s-20s Fixation 0s8s6s4s2s10s …… 46s 4s-20s Fixation 5 items 3 items 1 item

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. TargetsStandard Novels NeutralEmotional 84%8%4% Emotional Distracter Task

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

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

25. Emotional Distracter

26. Emotional Distractor Task Middle Frontal Gyrus (anterior)

27. Emotional Distractor Task Amygdala

28. Emotional Distracter

29. Anterior MFG Posterior IFG Emotional Distracter Task

30. Phase I (15s) Phase II (14s) Memoranda Probe 3.5s1.5s Novel stimuli (6s) +++ Emotional Distracters and Working Memory Dolcos and McCarthy, J Neurosci, 2006

31. Increased distractibility to emotional distracters linked to differential patterns of activity in the dorsal executive vs. ventral affective neural systems. MR signal change (%) dlPFC MR signal change (%) AMY Corrected Recognition Scores Scrambled SceneDistracters Neutral SceneDistracters Emotional SceneDistracters

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

33. Negative DistracterMeaningless DistracterNeutral Distracter

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

35. MFG CONTROLS SCZ PATIENTS

36. CONTROLS SCZ PATIENTS Ifg/BA 47

37. CONTROLS SCZ PATIENTS OF

38. CONTROLS SCZ PATIENTS FFG

39. CONTROLS SCZ PATIENTS Posterior Parietal

40. CONTROLS SCZ PATIENTS AMYGDALA

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

45. MFG IFG vmPFC Blocked Emotional Executive

46. Left MFG

47. Left IFG

48. Inferior Frontal Gyri

49. vmPFC

51. Inferior Parietal Lobule and VOTC

52. Left Parietal

53. Left VOTC

54. CONTROLS SCZ PATIENTS INSULA

55. CONTROLS SCZ PATIENTS ACG

56. CONTROLS SCZ PATIENTS Thalamus

57. CONTROLS SCZ PATIENTS Caudate