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Peter A. Bandettini, Ph.D. Section on Functional Imaging Methods fim.nimh.nih

Contentious Issues in fMRI . Peter A. Bandettini, Ph.D. Section on Functional Imaging Methods http:// fim.nimh.nih.gov Laboratory of Brain and Cognition & Functional MRI Facility http:// fmrif.nimh.nih.gov. The Undershoots Negative signal changes Relationship to neuronal activity

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Peter A. Bandettini, Ph.D. Section on Functional Imaging Methods fim.nimh.nih

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  1. Contentious Issues in fMRI Peter A. Bandettini, Ph.D. Section on Functional Imaging Methods http://fim.nimh.nih.gov Laboratory of Brain and Cognition & Functional MRI Facility http://fmrif.nimh.nih.gov

  2. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  3. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  4. The Undershoots Yacoub E, Le TH, Ugurbil K, Hu X (1999) Magn Res Med 41(3):436-41 Courtesy of Arno Villringer

  5. 20 sec Motor Stimulation 60 .6 CBF 40 .4 BOLD BOLD (% change) 20 .2 CBF (% change) 0 0 -20 -.2 0 20 40 60 80 100 Time (sec) BOLD post-stimulus undershoot A BOLD undershoot without a CBF undershoot could be due to a slow return to baseline of either CBV or CMRO2

  6. BOLD Signal Dynamics Courtesy Rick Buxton

  7. “During the poststimulusperiod, the amplitude and directionality (positive/negative) of the BOLD signal in both contralateral and ipsilateralsensorimotor cortex depends on the poststimulus synchrony of 8–13 Hz EEG neuronal activity, which is often considered to reflect cortical inhibition, along with concordant changes in CBF and metabolism.” “We suggest that the poststimulus EEG and fMRI responses may be required for the resetting of the entire sensory network to enable a return to resting-state activity levels.”

  8. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  9. Negative Signal Change Regions showing negative signal changes during cognitive tasks McKiernan, et al (2003), Journ. ofCog. Neurosci. 15 (3), 394-408

  10. Schmuel et al. (2002) Neuron, Vol. 36, 1195–1210

  11. B: BOLD C: Volume D: -Volume Goense, J., Merkle, H., and Logothetis, N.K.(2012). Neuron 76, 629–639.

  12. Bandettini, PA (2012). Neuron 76, 468-469

  13. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  14. Motor Cortex Auditory Cortex S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.”J. Cereb. Blood Flow and Met. 16, 1250-1254. J. R. Binder, et al, (1994). “Effects of stimulus rate on signal response during functional magnetic resonance imaging of auditory cortex.”Cogn. Brain Res. 2, 31-38 Parametric Manipulation

  15. fMRIresponses in human V1 are proportional toaveragefiringrates in monkey V1 Heeger, D. J., Huk, A. C., Geisler, W. S., and Albrecht, D. G. 2000.Spikes versus BOLD: What does neuroimaging tell us about neuronal activity? Nat. Neurosci. 3: 631–633. 0.4 spikes/sec -> 1% BOLD Rees, G., Friston, K., and Koch, C. 2000. A direct quantitative relationship between the functional properties of human and macaque V5. Nat. Neurosci. 3: 716–723. 9 spikes/sec -> 1% BOLD

  16. Logothetis et al. (2001) “Neurophysiological investigation of the basis of the fMRI signal”Nature, 412, 150-157

  17. Relationship to Neuronal Activity Muthukumaraswamy, S. D., Singh, K. D. (2008) NeuroImage 40 (4), pp. 1552-1560

  18. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  19. Linearity S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.”J. Cereb. Blood Flow and Met. 16, 1250-1254. Logothetis et al. (2001) “Neurophysiological investigation of the basis of the fMRI signal”Nature, 412, 150-157

  20. Brief “off” periods produce smaller decreases than expected. measured 2 1.5 0 linear Signal (%) 1 Linearity -2 measured 0.5 linear -4 0 0 5 10 15 20 time (s) Stimulus OFF duration (s) R.M. Birn, P. A. Bandettini, NeuroImage, 27, 70-82 (2005) Linearity Brief “on” periods produce larger increases than expected. measured linear 3 Linearity 2 Signal linear 1 0 1 2 3 4 5 time (s) Stimulus Duration (s) R. M. Birn, Z. Saad, P. A. Bandettini, NeuroImage, 14: 817-826, (2001)

  21. Brief ON 25% 50% 75% Brief OFF 8% ON 25% ON 50% ON 2 75% ON Signal 1.5 Linearity 1 0 5 15 10 time (s) 0.5 0 0.5 1 Duty Cycle Linearity Varying the Duty Cycle Deconvolved Response R.M. Birn, P. A. Bandettini, NeuroImage, 27, 70-82 (2005)

  22. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  23. task task

  24. Latency Variation… + 2 sec Latency - 2 sec Magnitude Venogram P. A. Bandettini, (1999) "Functional MRI" 205-220.

  25. sdelay = 107ms 1 run: 1% Noise 4% BOLD 256 time pts /run 1 second TR Number t -1000 -500 0 500 1000 delay estimate (ms) 500 400 16 sec on/off Smallest latency Variation Detectable (ms) (p < 0.001) 300 8 sec on/off 200 100 0 0 5 10 15 20 25 30 11 Number of runs

  26. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue. • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  27. Other controversial contrast mechanisms: • T2 contrast – Spin-echo • Blood Volume (VASO) • Diffusion • Neuronal Current

  28. Other controversial contrast mechanisms: • T2 contrast – Spin-echo • Blood Volume (VASO) • Diffusion • Neuronal Current Yacoub et al. NeuroImage 24 (3), pp. 738-750

  29. Other controversial contrast mechanisms: • T2 contrast – Spin-echo • Blood Volume (VASO) • Diffusion • Neuronal Current Yacoub et al. NeuroImage 37 (4), pp. 1161-1177

  30. Other controversial contrast mechanisms: • T2 contrast – Spin-echo • Blood Volume (VASO) • Diffusion • Neuronal Current H. Lu et al. Magnetic Resonance in Medicine 50 (2), pp. 263-274

  31. Other controversial contrast mechanisms: • T2 contrast – Spin-echo • Blood Volume (VASO) • Diffusion • Neuronal Current D. Le Bihan, et al Proceedings of the National Academy of Sciences of the United States of America 103 (21), pp. 8263-8268 K. Miller, et al Proceedings of the National Academy of Sciences of the United States of America 104 (52), pp. 20967-20972

  32. Other controversial contrast mechanisms: • T2 contrast – Spin-echo • Blood Volume (VASO) • Diffusion • Neuronal Current Magnetic Field Intracellular Current Surface Field Distribution Across Spatial Scales Adapted from: J.P. Wikswo Jr et al. J Clin Neurophy 8(2): 170-188, 1991

  33. EEG MR (7T) TTX Power decrease between PRE & TTX EEG : ~ 81% Decrease between PRE & TTX MR phase: ~ 70% Decrease between PRE & TTX MR magnitude: ~ 8% N. Petridou, D. Plenz, A. C. Silva, J. Bodurka, M. Loew, P. A. Bandettini, Proc. Nat'l. Acad. Sci. USA. 103, 16015-16020 (2006).

  34. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  35. Over the past year, a heated discussion about ‘circular’ or ‘nonindependent’ analysis in brain imaging has emerged in the literature. An analysis is circular (or nonindependent) if it is based on data that were selected for showing the effect of interest or a related effect. The authors of this paper are researchers who have contributed to the discussion and span a range of viewpoints. To clarify points of agreement and disagreement in the community, we collaboratively assembled a series of questions on circularity herein, to which we provide our individual current answers in <– 100 words per question. Although divergent views remain on some of the questions, there is also a substantial convergence of opinion, which we have summarized in a consensus box. The box provides the best current answers that the five authors could agree upon.

  36. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  37. Multi-sensory integration M.S. Beauchamp et al., Visual Auditory Multisensory

  38. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  39. Boynton (2005), News & Views on Kamitani & Tong (2005) and Haynes & Rees (2005)

  40. Lower spatial frequency clumping Kamitani & Tong (2005)

  41. The Undershoots • Negative signal changes • Relationship to neuronal activity • Linearity • Temporal precision • fMRI contrast mechanisms and sequences • Analysis circularity issue • How to handle high resolution • Basis of the decoding signal • How to best process/interpret resting state

  42. ICA Seed Voxel Seed Based Correlation from the Posterior Cingulate Cortex (PCC) Visual Visuospatial Executive Sensory Auditory Dorsal Pathway Ventral Pathway Greicius M D et al. PNAS 2003;100:253-258 De Luca, Neuroimage 29(4) 2006

  43. Hub Maps Identifying the brain’s most globally connected regions, M. W. Cole, S. Pathak, W. Schneider, NeuroImage 49, 2010, 3132-3148

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