Spatial & Temporal Properties (cont.) Signal and Noise

1. Spatial & Temporal Properties (cont.)Signal and Noise BIAC Graduate fMRI Course October 5, 2004

2. Temporal Resolution

3. What temporal resolution do we want? • 10,000-30,000ms: Arousal or emotional state • 1000-10,000ms: Decisions, recall from memory • 500-1000ms: Response time • 250ms: Reaction time • 10-100ms: • Difference between response times • Initial visual processing • 10ms: Neuronal activity in one area

4. Basic Sampling Theory • Nyquist Sampling Theorem • To be able to identify changes at frequency X, one must sample the data at 2X. • For example, if your task causes brain changes at 1 Hz (every second), you must take two images per second.

6. Aliasing • Mismapping of high frequencies (above the Nyquist limit) to lower frequencies • Results from insufficient sampling • Potential problem for designs with long TRs and fast stimulus changes • Also problem when physiological variability is present

7. Sampling Rate in Event-related fMRI

8. Costs of Increased Temporal Resolution • Reduced signal amplitude • Shorter flip angles must be used (to allow reaching of steady state), leading to reduced signal • Fewer slices acquired • Usually, throughput expressible as slices per unit time

9. Frequency Analyses t < -1.96 t < +1.96 McCarthy et al., 1996

10. Phase Analyses • Design • Left/right alternating flashes • 6.4s for each • Task frequency: • 1 / 12.8 = 0.078 McCarthy et al., 1996

11. Why do we want to measure differences in timing within a brain region? • Determine relative ordering of activity • Make inferences about connectivity • Anatomical • Functional • Relate activity timing to other measures • Stimulus presentation • Reaction time • Relative amplitude

12. Timing Differences across Regions Presented left hemifield before right hemifield (0-1000ms delays) fMRI vs RT (LH) Plot of LH signal as function of RH signal fMRI vs. Stimulus Menon et al., 1998

13. Activation maps Relative onset time differences Menon et al., 1998

14. Timing of mental events measured by fMRI • Miezin et al., 2000 • Subjects pressed button with one hand at onset of 1.5s stimulus • Then, pressed another button at offset of stimulus

15. V1 FFG Huettel et al., 2001

16. Secondary Visual Cortex (FFG) Primary Visual Cortex (V1) Subject 1 5.5s 4.0s Subject 2 Huettel et al., 2001

17. Width of fMRI response increases with duration of mental activity From Menon and Kim, 1999; after Richter et al, 1997

18. Independence of Timing and Amplitude Adapted from Miezin et al. (2000)

19. Linearity of the Hemodynamic Response

20. Linear Systems • Scaling • The ratio of inputs determines the ratio of outputs • Example: if Input1 is twice as large as Input2, Output1 will be twice as large as Output2 • Superposition • The response to a sum of inputs is equivalent to the sum of the response to individual inputs • Example: Output1+2+3 = Output1+Output2+Output3

21. Scaling (A) and Superposition (B) A B

22. Linear and Non-linear Systems A B C D

23. Possible Sources of Nonlinearity • Stimulus time course  neural activity • Activity not uniform across stimulus (for any stimulus) • Neural activity  Vascular changes • Different activity durations may lead to different blood flow or oxygen extraction • Minimum bolus size? • Minimum activity necessary to trigger? • Vascular changes  BOLD measurement • Saturation of BOLD response necessitates nonlinearity • Vascular measures combining to generate BOLD have different time courses From Buxton, 2001

24. Effects of Stimulus Duration • Short stimulus durations evoke BOLD responses • Amplitude of BOLD response often depends on duration • Stimuli < 100ms evoke measurable BOLD responses • Form of response changes with duration • Latency to peak increases with increasing duration • Onset of rise does not change with duration • Rate of rise increases with duration • Key issue: deconfounding duration of stimulus with duration of neuronal activity

25. The fMRI Linear Transform

26. Boynton et al., 1996 Varied contrast of checkerboard bars as well as their interval (B) and duration (C).

27. Boynton, et al, 1996

28. Boynton, et al, 1996

29. Differences in Nonlinearity across Brain Regions Birn, et al, 2001

30. SMA vs. M1 Birn, et al, 2001

31. Caveat: Stimulus Duration ≠ Neuronal Activity Duration

32. Refractory Periods • Definition: a change in the responsiveness to an event based upon the presence or absence of a similar preceding event • Neuronal refractory period • Vascular refractory period

33. Dale & Buckner, 1997 • Responses to consecutive presentations of a stimulus add in a “roughly linear” fashion • Subtle departures from linearity are evident

34. Intra-Pair Interval (IPI) Inter-Trial Interval (16-20 seconds) 6 sec IPI 4 sec IPI 2 sec IPI 1 sec IPI Single-Stimulus 500 ms duration Huettel & McCarthy, 2000

35. Methods and Analysis • 16 male subjects (mean age: 27y) • GE 1.5T scanner • CAMRD • Gradient-echo EPI • TR : 1 sec • TE : 50 msec • Resolution: 3.125 * 3.125 * 7 mm • Analysis • Voxel-based analyses • Waveforms derived from active voxels within anatomical ROI Huettel & McCarthy, 2000

36. Hemodynamic Responses to Closely Spaced Stimuli Huettel & McCarthy, 2000

37. Refractory Effects in the fMRI Hemodynamic Response Signal Change over Baseline(%) Time since onset of second stimulus (sec) Huettel & McCarthy, 2000

38. Refractory Effects across Visual Regions HDRs to 1st and 2nd stimuli in a pair (calcarine cortex) Relative amplitude of 2nd stimulus in pair across regions

39. Intra-Pair Interval (IPI) Inter-Trial Interval (16-20 seconds) 6 sec IPI 1 sec IPI Single-Stimulus

40. Single 05 10 15 20 25 30 35 40 45 50 55 60 6s IPI 1s IPI Figure 2 Mean HDRs L Signal Change over baseline (%) R Time since stimulus onset (sec)

41. Refractory Effect Summary • Duration • HDR evoked by a long-duration stimulus is less than predicted by convolution of short-duration stimuli • Present for durations < ~6s • Interstimulus interval • HDR evoked by a stimulus is reduced by a preceding similar stimulus • Present for intervals < ~6s • Differences across brain regions • Some regions show considerable departures from linearity • May result from differences in processing • Source of non-linearity not well understood • Neuronal effects comprise at least part of the overall effect • Vascular differences may also contribute

42. Using refractory effects to study cognition: fMRI Adaptation Studies

43. Neuronal Adaptation Grill-Spector & Malach, 2001 Several neuronal populations vs. homogeneous population Adaptation If neurons are insensitive to the feature being varied, then their activity will adapt. Viewpoint Sensitive Viewpoint Invariant

44. Lateral Occipital Posterior Fusiform

45. Is the refractory effect attribute specific? Boynton et al., 2003

46. A B Long Short Lateral Temporal-Occipital C D Peri-Calcarine Huettel, Obembe, Song, Woldorff, in preparation

47. Overall Summary • Spatial resolution • Advantages (of increasing) • Smaller voxels allow distinction among areas • Disadvantages • Require more slices, thus longer TR • Reduces signal per voxel • Temporal resolution • Advantages (of increasing) • Improves sampling of hemodynamic response • Disadvantages • Reduces # of slices per TR • May not be necessary for some designs • Non-linearity of hemodynamic response • Advantages (of phenomenon for design) • May be used to study adaptation • Disadvantages • Reduces power of short interval designs • Must be accounted for in analyses

48. Signal and Noise in fMRI

49. What is signal? What is noise? • Signal, literally defined • Amount of current in receiver coil • How can we control the amount of received signal? • Scanner properties (e.g., field strength) • Experimental task timing • Subject compliance (through training) • Head motion (to some degree) • What can’t we control (i.e., noise)? • Electrical variability in scanner • Physiologic variation (e.g., heart rate) • Some head motion • Differences across subjects

50. I. Introduction to SNR