1. Neural Imaging II: Imaging Brain Function ANA 516: February 13, 2007 Jane E. Joseph, PhD

2. Outline Physiological Basis of functional MRI (fMRI) Experimental Design and Data Analysis Issues Brief survey of fMRI studies in animals (mostly)

3. What is fMRI? One of a number of brain imaging techniques that reveal some dynamic, in vivo aspect of brain function.

4. What is fMRI? Spatial resolution Temporal resolution

5. What is fMRI? An INDIRECT measure of neural activity Measures relative concentrations of de-oxygenated blood Don’t need any contrast agents or radiation

6. Brief History of MRI / fMRI 1890 -- Roy and Sherrington postulated that changes in activity associated with brain function would lead to increases in blood flow in those regions 1945 – Bloch and Purcell share the Nobel prize for their work with magnetic resonance

7. Brief History of fMRI 1990 – Ogawa, et al. showed that MR images could be used to detect changes in blood oxygenation in vivo (in mouse brain) 1991 – First human fMRI studies

8. fMRI vs Other techniques Non-invasive which makes it ideal for: (1) developmental studies (kids can go in MRI scanner) (2) longitudinal studies (kids / people can go in multiple times) (3) aging studies Widely available (c.f. PET, TMS) No known health risks (c.f. PET)

9. fMRI vs Other techniques fMRI is NOT a good choice in certain situations: Many surgical implants cannot go in MRI scanner Presence of metal in body (or on body – tattoos, makeup) To measure neurotransmitters (use spectroscopy or PET)

10. fMRI vs Other techniques fMRI is NOT a good choice in certain situations: Claustrophobia To study gross motor behavior Certain patient populations with movement disorders (e.g PD)

11. Structural v. Functional MRI POSTERIOR

12. What is the physiological process or event that contributes to contrast in a functional image? POSTERIOR

13. Want to measure some aspect of neural activity, but fMRI does not do this directly Instead, fMRI is based on changes in oxygen consumption and blood flow, which are indirectly related to neural activity

14. Excitatory post-synaptic potentials (EPSPs), Inhibitory post-synaptic potentials (IPSPs), and Action potentials (APs) are not very metabolically demanding But the return to resting state does require energy!

15. How is blood flow related to neural activity? Increased neural activity causes release of vasoactive substances, which cause vessels (arterioles) to dilate – these effects can occur locally and upstream from the activity

16. How are these physiological changes measured with MRI? Deoxygenated hemoglobin (dHb) is paramagnetic (e.g. has unpaired electrons) due to losing O2 molecules dHb disrupts the magnetic field locally (dephasing spins shorten T2*)

17. More dHb  loss of MR signal Pure O 2 (100%) 20% O 2

18. oxygenated blood de-oxygenated blood

19. oxygenated blood de-oxygenated blood magnetic field gradient De-oxy hemoglobin disrupts magnetic field and causes a signal loss

20. oxygenated blood de-oxygenated blood magnetic field gradient Surplus of oxy hemogolobin  relatively lower concentration of deoxy hemoglobin in active regions

21. oxygenated blood de-oxygenated blood magnetic field gradient Less decrement in signal (OR small increments in signal) at activated sites

22. Blood Oxygenation Level Dependent Contrast (BOLD): 1. dHb is paramagnetic 2. Surplus of oxygenated blood at sites of activation

23. Early fMRI studies (Belliveau, et al. 1991) Look at blank screen Look at flashing checker board pattern This study not based on BOLD but used contrast !!!! Subtract Image A from Image B

24. First BOLD fMRI studies (Kwong, et al. 1992)

26. First BOLD fMRI studies (Blamire, et al. 1992)

27. Blamire, et al. (1992) showed that the BOLD response is delayed relative to the neural events associated with stimulus presentation (hemodynamic lag)  we are not measuring neural processes directly

28. BOLD response is related to neural activity (even though it is delayed)

29. A typical hemodynamic response (HDR): y-axis: Usually express in % change from baseline POSTERIOR

30. A typical functional brain activation map

31. Talairach Atlas ( Talairach & Tournoux, 1988 ) -y anterior posterior superior inferior left right +y+x -x +z -z Anterior commissure Posterior commissure

32. Brodmann’s Areas ( Brodmann, 1909 ) Lateral Surface Primary Sensory: - Visual (17) - Auditory (41) - Motor (4) - Somatosensory (1,2,3) Secondary: - Visual (18) - Auditory (42) Association: - Visual (19, 37) - Auditory (22) - Somatosensory (5)

33. Brodmann’s Areas ( Brodmann, 1909 ) Medial Surface Primary Sensory: - Olfactory (28, 38) Association: - Limbic (23, 24, 25, 26, 27, 29, 30, 31, 32, 33)

34. Experimental Design and Data Analysis Issues Technique constraints Limitations on experimental designs Advantages of fMRI

35. Technique Constraints BOLD signal ~= neuronal activity Poor temporal resolution No information about temporal order of events Spatial resolution

36. Limitations on Experimental Design No ferrous magnetic materials in scanner Use tasks that minimize amount of movement (gross motor tasks, speaking?) Auditory stimulus presentation may be masked by scanner noise Limits on length of experiments (hardware limitations and subject comfort) Subtraction Technique

37. Limitations on Experimental Design Subtraction Technique: –Must have a baseline condition with which to compare an experimental condition –May also have a control condition (or several) –What is a good baseline condition?

38. Advantages of fMRI Can do repeated measures  learning, practice, intervention, recovery of function Can test pediatric populations  developmental, longitudinal and aging studies Can look at individual-subject activation patterns

39. Some applications Imaging brain function in animals

40. Zhang et al. (2006). NeuroImage, 33, 636-643 Pharmacological MRI (phMRI) in MPTP lesioned rhesus monkeys

41. Functional MRI (fMRI) in alert, unanesthetized rhesus monkeys Joseph et al. (2006). Journal of Neuroscience Methods, 157, 10-24

43. Both monkeys showed novelty detection effects in the amygdala (only 1 monkey shown here)

44. BOLD imaging of spinal cord in rats Lilja et al. (2006). The Journal of Neuroscience, 26, 6330-6336 Hindlimb electrical stimulation  dorsal column activity on the ipsilateral side

45. BOLD imaging of spinal cord in humans Stracke et al. (2005). Neuroradiology, 47, 127-143 Stimulate different fingers  dorsal column activity in different dermatomes

46. MRI of insect brains!