m.vink@azu.nl - 2006

1. Functional Magnetic Resonance ImagingDr. Matthijs VinkRudolf Magnus Institute of Neuroscience University Medical Centre Utrecht Functional MRI Group Utrecht m.vink@azu.nl - 2006

2. Structure vs function Functional MRI (fMRI) studies brain function. MRI studies brain anatomy.

3. Localization of functions • Specific brain areas have specific cytoarchitecture • Localization of function (old idea) vs network function (new idea)

4. MRI vs fMRI Structural MRI  acquire image of whole brain in 8 minutes Functional MRI  acquire image of whole brain every 0.5 seconds

5. fMRI scans – example slices • scan technique • 3D PRESTO • resolution • 4*4*4 mm voxels • acquired scantime • 0.5 seconds

6. Functional MRI  acquire image of whole brain every 0.5 seconds task task task task task task task rest rest rest rest rest rest rest The idea behind fMRI Signal value over time in one voxel Example task-related activity in a voxel: Signal value

7. Moving fingers Moving tongue Watch flashing light Think words Short-term memory fMRI: Single subject data • fMRI developed from the 1990’s • Allows for single subject data

8. Background of fMRI • First BOLD-fMRI study published in 1992 by Ogawa et al • uses deoxygenated haemoglobin as contrast agent Advantages of fMRI: • no injection of chemicals (such as PET) • high spatial resolution (1-4 mm) • fast (0.5 sec per scan,average 2 sec) • widely available (MRI scanner in every hospital)

9. The MRI scanner... Promotional photo, Philips

10. The MRI scanner... is a very strong magnet! Not a promotional photo

11. Subject has to be metal-free Inhomogeneous magnetic field due to hairband Homogeneous magnetic field Scanner safety! Strict safety protocol

12. Background of fMRI – physics 1/2 Why do you need a magnet? No clear direction of protons

13. Background of fMRI – physics 1/2 Why do you need a magnet? B0 Apply magnetic field : (i.e. place subject in scanner…)

14. Background of fMRI – physics 1/2 Why do you need a magnet? B0

15. Background of fMRI – physics 1/2 Why do you need a magnet? B0

16. Background of fMRI – physics 1/2 Why do you need a magnet? B0

17. Background of fMRI – physics 1/2 Why do you need a magnet? B0 align with magnet (B0) (or against) # depends upon strength of B0

18. excitation relaxation precession motion in a magnetic field  radio wave is transmitted (echo)  Frequency  Phase Background of fMRI – physics 2/2 stability aligned with magnetic field (low energy state)

19. task task task task rest rest rest rest Basis of the fMRI signal - physiology • Place subject in scanner (protons align with magnet) • Start scanning while subject performs a task : • Rest periods  no activity (baseline) • During task  neuronal firing increases • Metabolism increases • consumption of glucose increases • consumption of oxygen increases • Bloodflow increases to supply oxygen (local magnetic field becomes very homogeneous) • Surplus of oxygen  BOLD fMRI signal increases (by 1-5 %)

20. t=0 s 100 Baseline: onset of stimulus t=1 s 99 Oxygen consumption Small field distortion t=6 s 102 Oxygen supply maximum fMRI signal Local field becomes homogeneous BOLD effect B lood O xygenation L evel D ependent effect

22. BOLD effect – where physics and physiology meet 1/2 oxyhaemaglobin low deoxyhaemglobin high oxyhaemaglobin high in-homogeneous field (out phase) homogeneous field (in phase) 3-4 mm

23. 102 BOLD effect – where physics and physiology meet 2/2 Mxy Signal (T2* relaxation) during task Dephasing (spin-spin interactions) Signal during rest 100 BOLD-contrast (activation) RF pulse time TE time (echo read-out) (B0)

24. The fMRI experiment

25. fMRI setup • Philips Gyroscan 1.5 Tesla • 1 Tesla = 10,000 Gauss • Earth’s magnetic field = 0.5 Gauss • 1.5 Tesla = 1.5 x 10,000  0.5 = 30,000 X Earth’s magnetic field Projection screen for computer tasks MRI-compatible button box mirror

26. task task task task task task task rest rest rest rest rest rest rest fMRI data analysis • Which brain regions are involved in performing the task? • Changes in the signal that correlate with the task (input function) • This is done in every voxel separately

27. fMRI preprocessing • Before the data (series of fMRI images) is ready for statistical analysis: • Correct for movement of the head during the experiment • To look at signal changes over time in the same voxel (brain region) • Transform the brain to a standard brain (enable group comparisons)

28. Motion correction 1/5 1. Position of the head over time scan 1 scan 2 … scan 99 … scan 820 time

29. Motion correction 2/5 2. Determine position of head during first scan scan 1 scan 2 … scan 99 … scan 820 time

30. Motion correction 3/5 3. Use first scan as reference position scan 1 scan 2 … scan 99 … scan 820 time

31. Motion correction 4/5 4. Determine motion correction parameters + scan 1 scan 2 … scan 99 … scan 820 time

32. Motion correction 5/5 5. Apply the parameters : resample the scans scan 1 scan 2 … scan 99 … scan 820 time Difficult to correct for effect of movement (in a magnetic field) on SNR throughout brain!

33. ? ? ? ? ? = = = = = Individual brains after normalization Transforming to standard brain Individual brains MNI template Can the brains of people be standardized at all?

34. task task task task task task task rest rest rest rest rest rest rest Basic fMRI image analysis The fMRI time-series data (eg 920 brain scans in 20 minutes): Look for task related activity in every voxel (activity that covaries with the task): Signal value over time in one voxel Example task-related activity in a voxel: Signal value

35. Model (X) Effects of interest (TASK) Effects of no-interest Multiple regression Signal in one voxel = + error Data (Y) (after realignment) Voxel-based statistics

36. task ViewMagic © Matthijs Vink Example : motor stimulation Regression-coefficient  height of signal increase compared to baseline T-value  significance of that increase compared to noise

37. fMRI tasks • Essential to develop an fMRI compatible task: • Avoid movements, talking, listening (motion artefacts, noise) • Keep it simple (interpretation of results) • Need for control task (helps interpretation) • Measure task performance (helps interpretation)

38. Schizophrenia Schizofrenie • symptoms: • positive (delusions, auditory hallucinations) • negative (social withdrawal, loss of initiative) • cognitive (memory, attention, information processing)

39. Language tasks Task (30 secs) Rest (30 secs) Task (30 secs) A G * S K * W F * … … Block design Verb generation (silent) What happens during rest? What happens during task?

40. Example : fMRI and language Healthy subjects : Language predominantly left

41. Language and schizophrenia Healthy subjects Schizophrenia patients Iris Sommer, work in progress

42. Interpretation Additional activation in right side in schizophrenia So what? How to figure out what that means? fMRI gives info on BOLD activation, but not function Apply repetitive TMS to right-sided language area to suppress auditory hallucinations Iris Sommer, work in progress

43. hallucinations delusions loss of initiative information overload Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia:

44. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions loss of initiative information overload

45. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions loss of initiative information overload

46. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions loss of initiative information overload

47. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions loss of initiative information overload

48. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions auditory loss of initiative information overload visual

49. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions auditory loss of initiative information overload visual

50. Example : fMRI as a tool for genetic research Hoe werkt dat bij schizofrenie? Schizophrenia: hallucinations delusions auditory loss of initiative information overload visual