1. First BIRN Cognitive Challenge Group Boston All-Hands Meeting October 12, 2004

2. To develop tasks that test for regional brain dysfunctions related to the progression and treatment of schizophrenia.

3. Outline 1.Challenge Tasks used for Human Phantom Studies 2.Revised Designs and Results 3.New Candidate Designs and Results

4. Tasks –Temporal Lobe / Auditory Processing Mismatch Task –Prefrontal Cortex / Executive Function Sternberg Memory Scanning Task

5. Control condition - 1 tone only (either 1,000 or 1,200 HZ) Mismatch condition - Standard Tone 1,000 Hz (95%), Deviant tones 1,200 Hz, (5%). Tones - 100 ms duration, 300 ms ISI, unattended (visual distracter task). MISMATCH PARADIGM Run 1: 8 min Run 2: 8 min. R MC 1k M R C 1.2k M R R R R R R R M R M M R C 1k M R R R R R R R M Visual Distracter Task on during all epochs Control 1k Control 1.2k Mismatch

6. MISMATCH PARADIGM Contrast of Mixed vs. ControlMixed Blocks

7. Learn -***- 3t A 1t 5t 3t A 5t 1t EncodeDelay14 probes 2.7”37.8” Sample Run…… (total time = 440.2 sec) 0 2 1 3 8 9 7 2 4...    ... 14 Arrows 37.8” fix 7 5 4 9 Prompt 2” Learn ***** (13.5 or 8.1 or 2.7”) 8.1” 2.7” 5t 3t 1t + + +.. Learn --*-- fix

8. dlPFC ROIs

9. Encode Timing

10. Probe Timing

12. Revised Designs 1.Revised SIRP 2.Auditory Oddball

13. Learn 3t 1t 5t 3t 5t 1t Encode14 probes 37.8 +.2 at end” Sample Run…… (total time = 360”, including DDAs) Order of WM blocks randomized 0 2 1 3 8 9 7 2 4... 7 * 5 * 4 * * 9 * * Prompt 1.5” +.5” Learn 5t 3t 1t + + +… Learn fix 6” 2.7” each, 1.1 appearance, 1.6 jitter, minimum pre.300, response time for each probe =~1.5s Average 12”, minimum 4”, max 20”, multiple of 2’’, randomized total fix time = 78” = 46”q block 2 blocks @ each WM load 6 blocks = 276” DDAs (6sec) fix(14s)fix 02 6 4

14. Revised SIRP

16. Auditory Oddball Duke-UNC 4T U Minn 3T

17. Auditory Oddball

18. Candidate Dual-Task Designs 1.Oddball + MisMatch 2.SIRP + MisMatch

19. Rest Oddball Fixation 30 sec Auditory tones: p(1000 Hz) = 0.9, p(1200 Hz) = 0.1 750 ms ISI, 100 ms duration Visual stimuli: block lengths = 30sec, ISI = 2000 ms 15 sec of fixation at beginning and end of run Repeat Dual Visual Oddball and Auditory Mismatch … … …

20. Two subjects acquired at 4.0 Tesla with TR = 1.5 sec Response evoked by Auditory Deviants

21. Oddball Blocks activate IPS and FFG Individual Subject with 4 task runs collected at 4.0 T with 1.5 sec TR

22. 1 975 1374 P ASV TGZR Rest Set Size 5Set Size 2 ****** ******** * 1 * 7 * ****** ******** A G T Y H Fixation 18 sec Auditory tones: p(1000 Hz) = 0.9, p(1200 Hz) = 0.1 750 ms ISI, 100 ms duration Visual stimuli: block lengths = 18 sec, ISI = 2000 ms 9 sec of fixation at beginning and end of run Repeat Dual Visual Sternberg and Auditory Mismatch

23. Reaction Time by Run for In-Set Probes Run

25. Deviant vs. Standard

26. Numbers vs. Rest (2 Item Memory Load)

28. Letters vs. Rest (5 Item Memory Load)

30. Letters vs. Numbers (5 vs. 2 Item Memory Loads)

31. 5 vs. 3 FFG IPS MFG

32. Task Cycle for Intraparietal Sulcus Five Items Load Two Items Load

33. Task Cycle for Fusiform Gyrus Five Items Load Two Items Load

34. Load 5 vs. 3

35. Summary of Analysis of Memory Scanning Task Robust activation of dlPFC and Parietal regions (the usual suspects) Similar patterns of activation for both 2 and 5 memory loads Differential load-related activation in FFG and IPS (primarily in left hemisphere – content specificity?) Differential load-related activation in dlPFC

36. Proposed New Task 1.Emotional Distracter Task

37. ... Emotional Distracter Task

38. Emotional Distracter

39. MFG IPS SMG PCG Emotional Distracter Task

40. -0.10% -0.05% 0.00% 0.05% 0.10% 0.15% 0.20% -303691215 Emotional novel Neutral novel Target -0.10% -0.05% 0.00% 0.05% 0.10% 0.15% 0.20% -303691215 Emotional novel Neutral novel Target Posterior IFG ACG FFG AMG Emotional Distracter Task

41. Anterior MFG Posterior IFG Emotional Distractor Task