1. What are we measuring in fMRI?
Marieke Schölvinck

2. Overview Physics of BOLD signal Physiology of BOLD signal
Magnetic fields and pulses
Magnetic properties of oxygen in blood
How we use this to generate a signal
Physiology of BOLD signal
How neurons cause blood flow increases
Implications for cognitive studies
Correlation with other measures of neural activity

3. It all starts with hydrogen…
physics
magnetic dipole moment (MDM)
MDMs align with / against uniform magnetic field Bo
small % more align with Bo  net magnetization

4. So what goes on in the scanner?
physics
Place hydrogen nuclei (brain) in a uniform magnetic field (scanner)
Apply radiofrequency (RF) pulse, normally at 90° to magnetic field. This ‘tips’ MDMs of hydrogen nuclei
MDMs of hydrogen nuclei are now
at 90° to main field (z), i.e. in x,y plane
Terminate RF pulse and let nuclei relax: MDMs
return to original (z) orientation; energy released
during relaxation is measured by receiver coil

5. Phase BEFORE the RF pulse: MDMs are not in phase DURING the RF pulse:
physics
BEFORE the RF pulse:
MDMs are not in phase
DURING the RF pulse:
MDMs in phase  strong signal in x,y plane
AFTER the RF pulse:
MDMs begin to dephase  signal decays
Two reasons for this dephasing:
inhomogeneities in the magnetic field
‘spin-spin’ interactions between neighbouring nuclei

6. Time to relax…
physics
time course for MDMs to return to original (z) orientation
time course of breakdown of magnetization
in the x,y plane due to spin-spin interactions
Different tissues have different T1 and T2 relaxation rates
in the x,y plane due to inhomogeneities in the magnetic field
T1 relaxation
T2 relaxation
T2* relaxation
BOLD…

7. We measure O2 ratios in blood
physics
BOLD (Blood Oxygenation Level Dependent) contrast: measures inhomogeneities in magnetic field due to changes in the level of O2 in the blood
deoxyhaemoglobin = magnetic! oxyhaemoglobin = not magnetic!
So we can use the change in fMRI signal
to infer the relative oxygenation of the blood!
High ratio deoxy:oxygenated blood
 fast decrease in MRI signal
Low ratio deoxy:oxygenated blood
 slow decrease in MRI signal

8. Summary of the physics
physics
MDMs of hydrogen nuclei align to magnetic field in scanner
RF pulse causes them to spin, in phase, in x,y plane
Once pulse has stopped they fall back to direction of magnetic field, dephasing as they do so
Dephasing takes various amount of time, depending in part on inhomogeneities in magnetic field
Inhomogeneities are caused by variable ratio of deoxygenated : oxygenated blood
Assumption: activity in brain area lowers this ratio and thereby decreases speed of decay of MRI signal

9. What causes BOLD?
physiology
The purpose of the increase in blood oxygenation is to feed neurons…
…so, what makes a neuron hungry?
(neurons can’t store much energy)
…and how does this change the blood flow?

10. Hungry brains 50-75% of energy
physiology
Pre-synaptic neuron
3Na 2K
3Na 2K
ATP
ATP
GLN
50-75% of energy
use is action potential driven; remainder is spent on housekeeping
ATP
3Na +
GLU
GLUTAMATE + H K +
Most energy is spent on the reuptake of glutamate and reversing ion movements! + Na 2K Na + Ca 2 +
3Na
ATP
Glial cell
Post-synaptic neuron

11. Vascular density Vascular density is proportional to synaptic density
physiology
Vascular density is proportional to synaptic density

12. Active control of blood flow
physiology

13. Neural activity  BOLD: complicated!
physiology
No easy relationship going from neural activity to BOLD
Relationship cannot only differ between brain area and level of activation, but also between subjects

14. … so what does it imply? No summation of BOLD signal!
physiology
No summation of BOLD signal!
No directly comparing different areas…
Different vasculature
Different neuromodulatory control
Different circuitry
BOLD [X] > BOLD [Y] does NOT mean neural activity [X] > activity [Y]!

15. What BOLD does not measure
physiology
Output of an area
Comparisons of activity between areas
Inhibitory synapses (GABA)
What BOLD does (presumably) measure
Excitatory synaptic activity (input to an area)
Local processing (reuptake of glutamate)
Changes in neuromodulatory substances

16. What does a blob in area X mean?
physiology
X has changed its local activity
Change of inputs arriving at X

17. Other ways to measure neural activity
physiology
Kim et al 2004

18. Summary of the physiology
Most energy is spent locally on synaptic processes
Blood flow is controlled by monoamines
BOLD does not measure output of an area, comparisons between areas, or inhibitory connections
Instead, BOLD measures changes in local activity and changes in input to an area
BOLD signal is most closely correlated with LFP signal

19. References Physics: Physiology:
Lipton ML (2007) MRI Physics: Understanding the Basics. Springer Verlag
Weishaupt et al (2003) How Does Mri Work? An Introduction to the Physics And Function of Magnetic Resonance Imaging. Springer Verlag
Physiology:
Logothetis NK et al (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature 412:
Attwell D & Iadecola C (2002) The neural basis of functional brain imaging signals Trends in Neurosciences 25:
Kim DS et al (2004) Spatial relationship between neuronal activity and BOLD functional MRI NeuroImage 21: