1. Moriah Thomason Lara Foland ‘n Me Radiological Sciences Laboratory Center for Advanced MR Technology* Stanford University School of Medicine Department of Radiology Neurosciences Program Towards Calibrating fMRI *

2. fMRI Calibration: Not needed here

3. Examples where quantifying activation may be important in drawing inferences about cognition: fMRI Calibration: Motivation Inter-group comparisons Age, health Longitudinal studies normal/abnormal development, therapy Multi-center studies fBIRN schizophrenia fMRI trial

4. BH Task: Children vs. Adults Thomason, et. al, 2005

5. BH Task: Children vs. Adults Thomason, et. al, 2005

6. BOLD contrast is indirect consequence of changes in regional metabolism Increased neuronal firing => increased blood flow => increased HbO2 & decreased (paramagnetic) Hb => increased MR signal Quantitative fMRI BOLD = Neuronal_Metabol HRF ( )NMR { }  HRF differences can modulate BOLD

7. Measurement of HRF - ER - Fourier-wtd block (FM) Breath holding - motivation - mechanism - prospects for calibration Outline

8. Definition: BOLD response to an impulsive stimulus may include neuronal and vascular responses -> use a cognitively simple task to reduce neuronal component may be nonlinear -> superposition does not hold Hemodynamic Response Function

9. HRF: Measure h(t) with 1s task motorauditory Glover, NI 1999 Finger tapping & tones at 3Hz, N=5

10. Spectral content of h(t)

11. Event related Fourier-wtd block (FM method) Nonlinearities Efficiency Measurement of HRF

12. Measurement of h(t): Fourier (FM) Design has on/off blocks of duration 4s, 6s, 8s, 10s, 12s, 16s, 20s, 30s, 40s, …4s

13. Measurement of h(t): Fourier (FM)

14. Analysis of Fourier Data: 1. GLM Model h(t): Then, calc. response is

15. GLM- Linear VisualAuditory

16. Response to epochs of finger tapping calculatedmeasured Glover, NI 1999 Finger tapping at 3Hz, 1.5T 1/3s, 2/3s, 1s, 2s, 4s, 8s, 16s

17. Sensorimotor Activation maps Glover, NI 1999

18. Second order Volterra series (Friston, 1998) Then, measurement is Nonlinearities

19. GLM- Linear vs. Nonlinear LinearNonlinear

20. GLM- Linear vs. Nonlinear

21. Event related Fourier-wtd block (FM method) Nonlinearities Efficiency Measurement of HRF

22. Measurement Efficiency ERFM  = 0.32  = 1.85 CNR(FM)/CNR(ER)= 6.1

23. Measurement Efficiency ER: 8 minFM: 6 min

24. Effect of HRF on Activation Gamma variate Linear HRF Nonlinear HRF

25. Adult/Child HRF

26. Effect of HRF on Activation Gamma variate Linear h JJEGAK AdultChild

27. Measurement of HRF - ER - Fourier-wtd block (FM) Breath holding - motivation - mechanism - prospects for calibration - fBIRN study - child/adult study of WM Outline

28. Breath-holding (BH) induces a systemic state change in brain oxygenation… Vascular Responsivity: BH … which results in a BOLD contrast change… … that does not derive from cognitive input. BOLD BH = NMR { HRF ( O2-state change ) } BOLD act = NMR { HRF ( CMRO2 change ) } |BOLD act | ~ |BOLD BH |  CMRO2 act

29. BOLD Signal Davis, PNAS (1998) Buxton, 2003 rCBF [HbO2] OEF [Hb] CMRO2 = OEF x rCBF x [HbO2]

30. BOLD Signal Kastrup (1999) Hoge (1999)

31. Block trial: 15s off/on - 8 cycles, 4 min, 15 s BH Task breathe normally 14sBreath in & hold 2sHold 14s

32. Activation BHSM

33. Vascular Responsivity: BH lf121103jshu112803

34. HbO2 vs. O2 in Lung

35. BH-induced BOLD signal Vascular res.   HR    rCBF  hypoxia Basal metab.  O 2 , CO 2, NO, H +   vasodilation   rCBF

36. BH Mechanism Thomason, et. al, 2005