What are we measuring in fMRI?

Marieke Schölvinck

Overview

Physics 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

magnetic dipole moment (MDM)

MDMs align with / against uniform magnetic field Bo

small % more align with Bo net magnetization

It all starts with hydrogen…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 nowat 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

So what goes on in the scanner?So what goes on in the scanner?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

Phasephysics

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

time course of breakdown of magnetization in the x,y plane due to inhomogeneities in the magnetic field

Time to relax…

T1 relaxation

T2 relaxation

T2* relaxation

BOLD…

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!

We measure O2 ratios in bloodphysics

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

Summary of the 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

physics

What causes BOLD?

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?

physiology

GLUTAMATE

Glial cell

3Na+

H+

K+

Na+

Post-synaptic neuron

Na+

Ca2+

GLU

GLN

ATP

2K3Na

ATP

2K3Na

ATP

2K3Na

ATP

Pre-synaptic neuron

50-75% of energy use is action potential driven; remainder is spent on housekeeping

Hungry brains

Most energy is spent on the reuptake of glutamate and reversing ion movements!

physiology

Vascular density

Vascular density is proportional to synaptic density

physiology

Active control of blood flowphysiology

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

… so what does it imply?

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]!

physiology

What BOLD does not measure Output of an area Comparisons of activity between areas Inhibitory synapses (GABA)

Excitatory synaptic activity (input to an area) Local processing (reuptake of glutamate) Changes in neuromodulatory substances

What BOLD does (presumably) measure

physiology

What does a blob in area X mean?

X has changed its local activity Change of inputs arriving at X

physiology

Other ways to measure neural activity

Kim et al 2004

physiology

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

physiology

References

Physiology:

Logothetis NK et al (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature 412:150-157

Attwell D & Iadecola C (2002) The neural basis of functional brain imaging signals Trends in Neurosciences 25:621-625

Kim DS et al (2004) Spatial relationship between neuronal activity and BOLD functional MRI NeuroImage 21:876-885

Physics:

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