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Resting-state fMRI: Algorithms and Applications to Brain Disorders

Resting-state fMRI: Algorithms and Applications to Brain Disorders. ZANG Yu-Feng 臧玉峰 M.D. zangyf@ gmail.com YAN Chao-Gan 严超赣 Ph. D. ycg.yan@gmail.com State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China. Outline. What is resting-state fMRI?

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Resting-state fMRI: Algorithms and Applications to Brain Disorders

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  1. Resting-state fMRI:Algorithms and Applications to Brain Disorders ZANG Yu-Feng 臧玉峰 M.D. zangyf@gmail.com YAN Chao-Gan 严超赣 Ph. D. ycg.yan@gmail.com State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China 1

  2. Outline • What is resting-state fMRI? • Computational methodology • Applications to brain disorders 2

  3. Functional MRI? • Generally • Blood oxygenation level dependent (BOLD) • Perfusion • Diffusion • Magnetic resonance spectroscopy (MRS) • …… 3

  4. Functional MRI? • More Specifically • BOLD-fMRI • Perfusion • Most Specifically • BOLD-fMRI 4

  5. Functional MRI? 5

  6. Task-state fMRI? Contrast within a scanning session is necessary! T C T C TC Design Expected signal 6

  7. Task-state fMRI What is activation? activated delta baseline or control 7

  8. Task-state fMRI What is abnormal activation for patients? Abnormal activated level? Abnormal delta Abnormal baseline? So, baseline is important! 8

  9. What is resting-state fMRI? • Eyes closed or open with no task • Continuously • Quite a few minutes or more • Not to fall asleep • Not to think of anything in particular • Low frequency fluctuation (LFF, 0.01 – 0.08 Hz) 9

  10. The nature of task BOLD “the haemodynamic response seems to be better correlated with the LFPs, implying that activation in an area is often likely to reflect the incoming input and the local processing in a given area rather than the spiking activity.” (Logothetis et al., 2001, Nature) BOLD ≈ LFP 10

  11. The nature of spontaneous BOLD “It was found that the impulse response function computed from LFP and BOLD under conditions of no stimulation can predict the response under stimulation conditions.” (Logothetis et al., 2001, Nature) Spontaneous BOLD ≈ spontaneous LFP 11

  12. Resting-state BOLD-fMRI signal reflects: However, also physiological noise (respiration, cardiovascular pulsation, etc) (Cordes et al., 2001; Birn et al., 2006) 12

  13. Outline • What is resting-state fMRI? • Computational methodology • Applications to AD studies 13

  14. Task-state fMRI • Functional segregation • (activation detection) • Functional integration • (inter-regional relationship or connectivity) 1 >> 2 14

  15. Most of resting-state fMRI studies：integration (connectivity) • Correlation: (Biswal et al., 1995; ……) • ICA: (Kiviniemi et al., 2003; van de Ven et al., 2004; Greicius et al., 2004) • Hierarchical Clustering: (Cordes et al., 2000; Salvador et al., 2005) • Self Organization Map: (Peltier et al., 2003) • .... 15

  16. The first Resting-state fMRI study (Biswal et al., 1995) Bilateral finger tapping (task vs. rest) Resting-state correlation of low frequency fluctuation (LFF, 0.01 – 0.08 Hz) (Courtesy of Dr. WENG Xu-Chu) 16

  17. Linear Correlation Spontaneous LFF was highly synchronous among: • Bilateral motor cortices (Biswal et al., 1995) • Bilateral visual cortices (Lowe et al., 1998; Kiviniemi et al., 2004) • Bilateral auditory cortices (Cordes et al., 2001) • Bilateral amygdala (Lowe et al., 1998) • Bilateral thalamus (Stein et al., 2000) • Language cortices (Hampson et al., 2002) • Default mode network (Greicius et al., 2003; Fox et al., 2005..) 17

  18. A default mode of brain function (Raichle et al., 2001) PCC, MPFC, IPL etc., 1) Consistently show task-independent deactivation (TID) during a wide range of tasks with cognitive demand 2) Highest metabolic rate in the brain during resting state 1) 2) 18

  19. Functions of the default mode network • Intrinsic activities (Fransson, 2005): • Self-reflection, self-referential processing, self awareness • Task-unrelated thought (TUT) • Mind wandering or daydreaming • Streams of consciousness • Memory retrieval of autobiographic events • …… 19

  20. Most of resting-state fMRI studies：integration (connectivity) • Correlation: (Biswal et al., 1995; ……) • ICA: (Kiviniemi et al., 2003; van de Ven et al., 2004; Greicius et al., 2004) • Hierarchical Cluster: (Cordes et al., 2000; Salvador et al., 2005) • Self Organization Map: (Peltier et al., 2003) • .... 20

  21. Independent Component Analysis (ICA) Spatial ICA for fMRI data: separate a mixture of a 4D data into a set of spatially independent components (McKowen et al., 1998) 21

  22. Spatial ICA for resting-state fMRI Vascular component Visual component (Kiviniemi et al., 2000) 22

  23. “Integrative” is really good, but: Decreased functional connectivity Question: Is A, B, C, or……abnormal? 23

  24. Only A few resting-state fMRI studies：Segregation • rms, power spectrum, ALFF:(Biswal et al., 1995; Li et al., 2000; Kiviniemi et al., 2000; Zang et al., 2007) • TCA:(Liu et al., 2000; Morgan et al., 2004) • Regional Homogeneity:(Zang et al., 2004) • Multiple Regressors:(Fransson, 2005) • Autoregressive Noise Model:(Cordes et al., 2005) • Fractional Gaussian Noise:(Maxim et al., 2005) 24

  25. rms, power, ALFF For a given frequency: root mean square (rms) standard deviation amplitude rms: white matter vs. gray matter = 0.6 : 1 (Biswal et al., 1995; Li et al., 2000) Square root of the power 25

  26. rms, power, ALFF • Power spectrum: Higher power at 0.033Hz in visual area(Kiviniemi et al., 2000) 26

  27. Amplitude of Low Frequency Fluctuation (ALFF)(Zang et al., 2007; Yang et al., 2007) TR 400 ms 1.25 Hz 0.01-0.08 Hz Steps: square root, average of 0.01-0.08 Hz, standardization by global mean 27

  28. ALFF PET (Raichle et al., 2001) ALFF (Zang et al., 2007) noise 28

  29. Abnormal ALFF ADHD vs. controls (n=13) (n=12) (Zang et al., 2007) Early AD vs. controls (He Y et al., 2007)(Please see below for details) 29

  30. Improvement: fractional ALFF Suprasellar cistern PCC 30

  31. Improvement: fractional ALFF (Zou et al., 2008) 31

  32. Regional Homogeneity (ReHo) Similarity or coherence of the time courses within a functional cluster (Zang et al., 2004) 32

  33. ReHo: motor task state vs. pure resting state(Zang et al., 2004) Rest > Motor Motor > Rest a) Higher ReHo in bilateral primary motor cortices during motor task b) Higher ReHo in default mode network (PCC, MPFC, IPL) during rest (Raichle et al., 2001; Greicius et al., 2003) 33

  34. ReHo applications to brain disorders • ADHD: Zhu et al., 2005, 2007; Cao et al., 2006 • AD/MCI: He et al., 2007; Bai et al., 2008 • Schizophrenia: Liu et al., 2006, Shi et al., 2007 • Aging: Wu et al., 2007 • PD: Wu et al., 2008 • Depression: Yuanet al., 2008 34

  35. Outline • What is resting-state fMRI? • Computational methodology • Applications to brain disorders 35

  36. RESTing-state fMRI data analysis toolkit (REST) By Song et al., http://www.restfmri.net 36

  37. Data Processing Assistant for Resting-State fMRI (DPARSF) Yan CG* and Zang YF* (2010) DPARSF: a MATLAB toolbox for "pipeline" data analysis of resting-state fMRI. Frontiers in Systems Neuroscience. 4(13) http://www.restfmri.net 37

  38. Outline • What is resting-state fMRI? • Computational methodology • Applications to brain disorders 38

  39. Some issues about resting-state fMRI • Definition and instruction? • Sampling rates (TR) • Length • Standard method for data analysis? 39

  40. Definition and Instruction? • Eyes closed or open with no cognitive task • Continuously • Not to fall asleep • Not to think of anything particular ill defined! 40

  41. Different resting conditions? The functional connectivity patterns of the default mode network was minimally disturbed during different resting conditions with limited cognitive demand (Greicius et al., 2003; Fransson, 2005; Fox et al., 2005) Fox et al., 2005 41

  42. Different resting conditions? Functional connectivity maps Significantly different between different resting conditions with limited cognitive demand Yan et al., PLoS ONE 2009 42

  43. Different resting conditions? Regional activity (ALFF) Significantly different between different resting conditions with limited cognitive demand Yan et al., PLoS ONE 2009 43

  44. Different resting conditions? Suggestion: eyes closed for patients studies 44

  45. Is the resting block a resting-state? In block design Long resting No study has compared directly between them yet 45

  46. Is the resting block a resting-state? Stimulus Peak: 4-8 s 20 - 30 s BOLD Post undershoot: > 15 s 46

  47. Some issues about resting-state fMRI • Definition and instruction? • Sampling rates (TR) • Length • Standard method for data analysis? 47

  48. Some issues about resting-state fMRI Sampling rates (TR) Nyquist sampling theorem: Shorter TR (<400 ms, >2.5 Hz) for heart beating (around 1.3 Hz) 48

  49. Sampling rate and physiological noise But for respiration (around 0.3 Hz)? Is TR <1.5 s fast enough? Courtesy of SONG Xiao-Wei Simultaneous recording of respiration and heart beat to remove physiological noise (Hu et al., 1995, MRM) 49

  50. Some issues about resting-state fMRI • Definition and instruction? • Sampling rates (TR) • Length • Standard data analysis? 50

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