Sonia Poltoratski Vanderbilt University

1. fMRI Sonia Poltoratski Vanderbilt University

2. unbridled joy brain picture knowledge data intro psych analysis ...is the wild wild west what is BOLD? crippling depression

3. Outline: • MR Physics • BOLD signal • Basics of Analysis • Evolution • Good & Bad Practices

4. MR Physics • MR in humans = proton nuclear magnetic resonance, which detects the presence of hydrogen nuclei • Since the single proton of hydrogen in unbalanced, normal thermal energy causes it to spin about itself electron - + proton

5. Spins μ J • The proton’s positive charge generates an electrical current • In a magnetic field, this loop current induces torque, called the magnetic moment (μ) • The proton’s odd-numbered atomic mass gives it an angular momentum (J) + + + + + + + + + + proton

6. Net magnetization (M) Negligible under normal conditions

7. magnetic field B0

8. Proton Precession • Spinning objects respond to applied forces by moving their axes perpendicular to the applied force

9. Proton Precession • Spinning objects respond to applied forces by moving their axes perpendicular to the applied force precession axis magnetic field spin axis

10. Proton Precession magnetic field parallel state (low energy level) anti-parallel state (high energy level)

11. Net Magnetization (M) longitudinal M magnetic field transverse

12. Net Magnetization (M) Increasing magnetic field  increase in net magnetization The Zeeman Effect high energy state energy ΔE low energy state magnetic field strength

13. Signal Generation excitation B1 magnetic field B0 photons: electromagnetic fields oscillating at the resonate (Larmor) frequency of hydrogen

14. Signal Generation: Net M excitation B1 M magnetic field B0 flip angle θ

15. Signal Reception reception magnetic field B0 decaying, time-varying signal that depends on the molecular environment of the spins

16. Signal Reception T1 recovery(longitudinal relaxation): Individual spins return to their low-energy state, and net M becomes again parallel to the main field T2 decay (transverse relaxation): Immediately after excitation, spins precess in phase This coherence is gradually lost Images depict the spatial distribution of these properties - BOLD

17. T1 Relaxation Times Fat White Matter Grey Matter CSF

18. T2 Decay Times Fat White Matter CSF Grey Matter

19. Image Formation • Magnetic gradient: spatially varying magnetic field • Adding a second gradient field causes spins at different locations to precess at different frequencies in a predictable manner Paul C. Lauterbur and Sir Peter Mansfield at the 2003 Nobel Prize Ceremony

20. Image Formation longitudinal magnetization slice excitation transverse magnetization 2D spatial encoding acquired MR signal in k-space 2D inverse Fourier transform 2D MR image

21. Slice Excitation ƒ resonant frequency vs. position slice direction

22. Slice Excitation ƒ resonant frequency vs. position when gradient is applied frequency range of RF pulse slice direction excited slice

23. Spatial Encoding 2D A gradient field that differs along two dimensions results in a unique frequency assigned to each location in the space, influencing the location’s spin phase • Phase encoding gradient: turned on before data acquisition so that spins accumulate differential phase offset over space • Frequency encoding gradient: turned on during data acquisition so that the frequency of spin precession changes over space Resulting data is in units of spatial frequency, which can be converted into units of distance via inverse Fourier transform Echo Planar Imaging(EPI) allows us to collect an entire imagine in milliseconds, either following 1 excitation (single-shot) or several (multi-shot)

24. T1-Weighted Image T2-Weighted Image

25. Pop Quiz! MRI data acquisition The experimental data were collected at the Vanderbilt University Institute for Imaging Science using a 3T Philips InteraAchieva MRI scanner with an eight-channel head coil. The functional data were acquired using standard gradient-echo echoplanar T2*-weighted imaging with 28 slices, aligned approximately perpendicular to the calcarine sulcus and covering the entire occipital lobe as well as the posterior parietal and posterior temporal cortex (TR, 2 s; TE, 35 ms; flip angle, 80°; FOV, 192 x192; slice thickness 3 mm with no gap; in-plane resolution, 3 x3 mm). In addition to the functional images, we collected a T1-weighted anatomical image for every subject (1 mm isotropic voxels). A custom bite bar system was used to minimize the subject’s head motion. Keitzmann, Swisher, Konig, & Tong (2012)

26. Pop Quiz! MRI data acquisition The experimental data were collected at the Vanderbilt University Institute for Imaging Science using a 3TPhilips InteraAchieva MRI scanner with an eight-channel head coil. The functional data were acquired using standard gradient-echo echoplanarT2*-weighted imaging with 28 slices, aligned approximately perpendicular to the calcarine sulcus and covering the entire occipital lobe as well as the posterior parietal and posterior temporal cortex (TR, 2 s; TE, 35 ms; flip angle, 80°; FOV, 192 x192; slice thickness 3 mm with no gap; in-plane resolution, 3 x3 mm). In addition to the functional images, we collected a T1-weighted anatomical image for every subject (1 mm isotropic voxels). A custom bite bar system was used to minimize the subject’s head motion. Keitzmann, Swisher, Konig, & Tong (2012)

27. Outline: • MR Physics • BOLD signal • Basics of Analysis • Evolution • Good & Bad Practices

28. BOLD signal Blood-Oxygen-Level-Dependent Contrast (Thulborn et al., 1982; Ogawa, 1990) • Deoxygenated • Hemoglobin • Paramagnetic (significant magnetic moment) • 20% greater magnetic susceptibility, which impacts T2 decay Oxygenated Hemoglobin Diamagnetic (no unpaired electrons or magnetic moment)

29. BOLD signal Blood-Oxygen-Level-Dependent Contrast (Thulborn et al., 1982; Ogawa, 1990) • Deoxygenated • Hemoglobin • Paramagnetic (significant magnetic moment) • 20% greater magnetic susceptibility, which impacts T2 decay Oxygenated Hemoglobin Diamagnetic (no unpaired electrons or magnetic moment) The more deoxygenated blood is present, the shorter the T2 Difference emerges at ~ 1.5T

30. Ogawa (1990) • Blood oxygen content in rodents reflected in T2-weighted images • Metabolic demand for oxygen (confirmed by concurrent EEG) is necessary for BOLD contrast “ During an MRI experiment with an anesthetized mouse, I saw most of the dark lines disappear when the breathing air was switched to pure O2 in order to rescue the mouse as it appeared to start choking. This observation rang a bell. ”

31. fMRI vs. Other Methods MEG & ERP PET brain map column layer neuron dendrite synapse fMRI Optical Imaging Natural Lesions TMS Induced Lesions Multi-unit recording log size Single Unit Patch Clamp Light Microscopy millisecond second minute hour day log time

32. Outline: • MR Physics • BOLD signal • Basics of Analysis • Evolution • Good & Bad Practices

33. Voxels 1mm x 1mm x 1.5mm voxels 7mm x 7mm x 10mm voxels (Smith, 2004)

34. Preprocessing Stages • Slice-timing correction: correcting for differences in acquisition times within a TR • Motion correction: re-alignment of images across the session • Spatial smoothing: blurring of neighboring data points, akin to low-pass filtering.

35. Preprocessing Stages • Mean intensity adjustment: normalization of signal to account for global drifts over time • Temporal high-pass filtering: removal of low-frequency drifts in time course

36. Hemodynamic Response Function peak stimulus percent MR signal change undershoot initial dip -10 -5 0 5 10 15 20 25 time (s)

37. Modeling the Waveform J J J block design HRF fit this model to the time series of each voxel

38. General Linear Modeling Y= X. β+ ε estimated parameters error observed data at a single voxel design matrix test if the slope of β is different from zero

39. = t stat at each voxel anatomical scan image my FFA!

40. Outline: • MR Physics • BOLD signal • Basics of Analysis • Evolution • Good & Bad Practices

41. Nature (2012)

42. Voxel Resolution Kanwisher, McDermott, & Chun (1997): 3.25 x 3.25 x 6 mm McGugin et al. (2013): 1.25 x 1.25 x 1.25 mm

43. TR Duration (not my) unpublished data removed for web use (Tong Lab data) 7Tesla, TR = 200ms

44. Outline: • MR Physics • BOLD signal • Basics of Analysis • Evolution • Good & Bad Practices

45. ‘The Seductive Allure of Neuroimaging’ “ Non-experts judge explanations with neuroscience information as more satisfying than explanations without neuroscience, especially bad explanations. ” (Weisberg et al., J Cog Neuro 2008)

46. The Nader Effect

48. Pitfalls in fMRI • Study Design • What is your contrast? • What conclusions can we draw from fMRI activation? • Statistical Analysis vs

49. Correcting for Multiple Comparisons (Bennett et al. 2010)

50. Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, & Social CognitionVul et al. (2009) Voodoo Correlations in Social Neuroscience • Noticed R > 0.8 correlations, seemingly higher than possible under constraints of fMRI and variability of personality measures • Non-independence error: • Selecting a small number of voxels based on some trait • Only reporting the correlation of the trait to those voxels • 54% of surveyed papers, including those published in Science, Nature, and Neuron