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Peter A. Bandettini, Ph.D. Unit on Functional Imaging Methods

Peter A. Bandettini, Ph.D. Unit on Functional Imaging Methods. March 1999 – March 2003. Measured Signal. Neuronal Activation. ?. ?. ?. ?. Hemodynamics. Noise. MRI Physics. Technology. Neuroscience Applications. Direct measures of neuronal activity. Clinical Applications.

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Peter A. Bandettini, Ph.D. Unit on Functional Imaging Methods

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  1. Peter A. Bandettini, Ph.D. Unit on Functional Imaging Methods March 1999 – March 2003

  2. Measured Signal Neuronal Activation ? ? ? ? Hemodynamics Noise

  3. MRI Physics Technology Neuroscience Applications Direct measures of neuronal activity Clinical Applications Methodology Physiologic and neuronal manipulation

  4. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  5. Question: What is the “true” spatial extent of BOLD contrast? Paradigm: Repeated averaging of simple visual task

  6. Future: • Determine if “extra” activation is vascular or (sub-threshold) neuronal • Perform experiment at 7T and/or with 16 channel system • Ultimate aim: to differentially map subthreshold vs. suprathreshold activity

  7. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  8. measured linear BOLD Response Signal Stimulus timing 0.25 s 0.5 s 1 s 2 s 20 s time (s) Question 1: Do BOLD nonlinearities exhibit spatial heterogeneity? Paradigm: Stimulus duration modulation from 50 ms to 20 sec.

  9. Nonlinearity Magnitude Latency

  10. Question 2: Is the source neuronal or hemodynamic? • Neuronal • Hemodynamic • Oxygen extraction • Blood flow and volume dynamics Oxygen Extraction Flow In Flow Out D Volume

  11. Evidence from Logothetis et al… Logothetis et al. (2001) “Neurophysiological investigation of the basis of the fMRI signal” Nature, 412, 150-157. P. A. Bandettini and L. G. Ungerleider, (2001) “From neuron to BOLD: new connections.” Nature Neuroscience, 4: 864-866.

  12. Ongoing work: Modulation of neuronal activation • Planned work: • Single unit monkey recordings with identical stimuli • Identical experiments with MEG in humans

  13. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  14. Question3: How does neuronal activity integrate to influence BOLD magnitude? Initial Observation: For a perceptual decision making task, random dot coherence was varied from 0% to 50%. A non-monotonic BOLD effect was observed in MT. Heekeren, Marrett, et al.

  15. Proposed explanation: Neuronal activity intensity and number of active neurons have different effects on BOLD contrast. Rainer et al. (2001) Planned work: Deconstruct effect by using stimuli which separately modulate the intensity and number of active neurons. Heekeren et al.

  16. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  17. The major obstacle in BOLD contrast temporal resolution: + 2 sec Latency - 2 sec Magnitude

  18. 9.0 seconds 15 seconds 500 msec 500 msec 20 30 10 Time (seconds) Relative dynamics obtained by precise activation timing modulation Preliminary results: (with Savoy et al. ~ 1995) Hemi-Field Experiment Left Hemisphere Right Hemisphere

  19. 500 ms 500 ms RightHemifield Left Hemifield + 2.5 s - = 0 s - 2.5 s

  20. Cognitive Neuroscience Application:

  21. A A A B B B Word vs. Non-word 0o, 60o, 120o Rotation Regions of Interest Inferior Frontal Gyrus Precentral Gyrus Middle Temporal Gyrus

  22. w 1 a Amp. d 0 0 0 5 10 15 0 5 10 15 Estimation of Delay, Width & Amplitude Conv. time (s) Adjust d, w, a to improve fit (Nelder-Mead simplex method) 20 0 0 5 10 15

  23. p < 10 -6 p < 10 -5 p < 10 -4 p < 10 -3 p < 10 -2 Time Difference In msec > 300 250 to 300 200 to 250 150 to 200 100 to 150 Lexical effect Rotational effect Magnitude Delay Width Words > Nonwords Nonwords > Words 0 deg > 120 deg 120 deg > 0 deg

  24. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  25. Preliminary models suggest that magnetic field changes on the order of 0.1 to 1 nT are induced (at the voxel scale) in the brain. • These changes induce about a 0.01 Hz frequency shift or 0.09 deg (@ TE = 30 ms) phase shift. • Question: Is this detectable?

  26. Z X BR<2nT BR<0.2nT

  27. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  28. 25 mV 10 s In Vitro Results Newborn rat brains have been found to exhibit spontaneous and synchronous firing at specific frequencies Cortex Striatum Subthalamic nucleus Globus Pallidus Plenz, D. and S.T. Kital. Nature, 1999. 400: p. 677-682.

  29. 1 2 Results Culture CSF CSF Culture # # * * * * FSE image Hz Hz Active state: 10 min, Inactive state: 10 min after TTX admin. *: activity #: scanner pump frequency Petridou et al.

  30. Phase v=0.12Hz Closed Open Power spectra Eyes closed Eyes open 0.5 Hz 0.5 Hz

  31. Topics Discussed in this Presentation • The relationship between BOLD contrast and neuronal activity • Spatial extent • Transient dynamics • Neuronal population vs intensity effects • Further extraction of neuronal information from BOLD contrast • Hemodynamic width and latency • Direct neuronal activity imaging • Phantom results • Preliminary in vitro and human results • Future themes

  32. Future Themes • Mapping of neuronal sub-populations • Quantitation/Calibration • Fluctuation Characterization • Free-behavior designs • Neuronal current imaging

  33. UFIM&FMRIF Director: Peter Bandettini Staff Scientists: Sean Marrett Jerzy Bodurka Frank Ye Wen-Ming Luh Computer Specialist: Adam Thomas Post Docs: Rasmus Birn Hauke Heekeren David Knight Patrick Bellgowan Ziad Saad Graduate Student: Natalia Petridou Post-Bac. IRTA Students: Elisa Kapler August Tuan Dan Kelley Hahn Nguen Visiting Fellows: Sergio Casciaro Marta Maieron Guosheng Ding Clinical Fellow: James Patterson Psychologist: Julie Frost Summer Students: Hannah Chang Courtney Kemps Douglass Ruff Carla Wettig Kang-Xing Jin Program Assistant: Kay Kuhns Scanning Technologists: Karen Bove-Bettis Paula Rowser

  34. JB AT NP ZS W-M L FY RB MM PB PFB DK SM DKn HH EK ATn Technology Methodology Physicist Engineer Computer Scientist Statistician Clinician Basic Neuroscientist Cog Neuroscientist Physiologist Interpretation Applications

  35. Extra..

  36. Diff. tensor Technology Mg+ 7T >8 channels 1.5T,3T, 4T EPI on Clin. Syst. Venography Real time fMRI EPI SENSE Nav. pulses Local Human Head Gradient Coils Quant. ASL Z-shim Baseline Susceptibility MRI Dynamic IV volume Spiral EPI ASL Current Imaging? BOLD Simultaneous ASL and BOLD Multi-shot fMRI Correlation Analysis CO2 Calibration Methodology Motion Correction Mixed ER and Blocked Parametric Design Multi-Modal Mapping Surface Mapping Baseline Volume Free-behavior Designs ICA Phase Mapping Mental Chronometry Linear Regression Multi-variate Mapping IVIM Deconvolution Fuzzy Clustering Event-related BOLD models PET correlation Interpretation IV vs EV ASL vs. BOLD Bo dep. Pre-undershoot PSF of BOLD Linearity mapping TE dep Resolution Dep. Extended Stim. Blood T2 Post-undershoot Metab. Correlation Linearity SE vs. GE CO2 effect Optical Im. Correlation Hemoglobin Fluctuations NIRS Correlation Veins Balloon Model Electrophys. correlation Inflow Complex motor Applications Memory Imagery Emotion Language Children Drug effects Motor learning Tumor vasc. BOLD -V1, M1, A1 Presurgical Ocular Dominance Attention Volume - Stroke Clinical Populations V1, V2..mapping Priming/Learning D Volume-V1 Performance prediction Plasticity Face recognition 36 82 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02

  37. A practical implication…. Rapid event-related design with varying ISI 8% ON 25% ON 50% ON 75% ON

  38. 8% ON Measured Blocked Response 8% ON 25% ON 50% ON 25% ON Signal 50% ON 75% ON 75% ON Signal 0 10 20 30 40 0 5 15 10 time (s) time (s) Estimated Impulse Response Predicted Responses to 20 s stimulation

  39. Brain activity correlated with SCR during “Rest”

  40. 100 a Response amplitude b 50 0 Stimulus Duration 0 1000 2000 3000 Results – constant gratings Simulation 3 Measured Amplitudes 2 a = initial slope Amplitude (%) 1 b = final slope 0 0 1000 2000 3000 200 Stimulus Duration (ms) Estimated Neuronal activity

  41. P. A. Bandettini, R. W. Cox. Functional contrast in constant interstimulus interval event - related fMRI: theory and experiment. Magn. Reson. Med. 43: 540-548 (2000).

  42. 20, 20 12, 2 10, 2 8, 2 6, 2 4, 2 2, 2 Contrast to Noise Images ( ISI, SD ) S1 S2 P. A. Bandettini, R. W. Cox. Functional contrast in constant interstimulus interval event - related fMRI: theory and experiment. Magn. Reson. Med. 43: 540-548 (2000).

  43. SD = 4000 s. SD = 1000 ms. SD = 250 ms. Detectability – constant ISI SD – stimulus duration ISI – inter-stimulus interval Detectability 0 5 10 15 20 25 30 35 40 Average ISI (s)

  44. Detectability vs. Average ISI SD = 4000 s. Detectability SD = 1000 ms. SD = 250 ms. 0 5 10 15 20 25 30 35 40 average ISI (s) R. M. Birn, R. W. Cox, P. A. Bandettini, Detection versus estimation in Event-Related fMRI: choosing the optimal stimulus timing. NeuroImage 15: 262-264, (2002).

  45. Estimation accuracy vs. average ISI 20 15 SD = 250 ms. Estimation Accuracy 10 SD = 1000 ms. SD = 4000 ms. 5 0 0 5 10 15 20 25 30 35 40 average ISI (sec) R. M. Birn, R. W. Cox, P. A. Bandettini, Detection versus estimation in Event-Related fMRI: choosing the optimal stimulus timing. NeuroImage 15: 262-264, (2002).

  46. Venograms (3T)

  47. Signal / Thermal Noise Signal / Physiologic Noise Signal to Noise Ratio Optimal for fMRI Resolution, Speed, Surface Coils, Field Strength, etc..

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