The Basics of fMRI

Overview:

• Physiological origins (BOLD)• Physical origins (MRI)• Physical measurements of BOLD• Paradigm (task) design• Analysis of task-activated fMRI• Resting fMRI

Physiological origins

Neurophysiological coupling: neuronal activity blood oxygenation

stimulus

Change inoxy:deoxy ratio

Logothetis et al. (2001) Nature 412: 150

LFP – local field potentialsMUA – multi unit activitySDF – spike density function

Physiological originsLocal hemodynamic changes [ROY, C. W., SHERINGTON, C. S. On the regulation of the blood-supply of the brain. J. Physiol. (Lond.) 11: 85-108, 1890.]

• Increase in local blood flow (+50%)

• Increase in local blood volume

• Small increase in oxygen consumption (+15%)

• Increased flow means reduced O2 extraction ‘hence’ oversupply of blood

• Haemodynamic response function (HRF)

Physical origins

Proton (1H) has a magnetic moment which can be non-toxically manipulated with transitory magnetic fields (B1) and RF energy to produce images of its local environment.

Structural MRI

Physical originsAmplitude of signal determined by: • Proton density: more protons, more signal • T1 (spin-lattice relaxation): Stimulated by local magnetic

field fluctuations due to magnetic properties of other molecules.

• T2*: Enhanced dephasing due to inhomogeneities in local magnetic field (inc. B0) – susceptibility.

• T2 (spin-spin relaxation): residual dephasing during dephase-rephase period

• Contrast agents: changing local susceptibility

Physical origins

Definitions

• Time to Repetition (TR): The TR is the time between consecutive sequence initiations

• Time to Echo (TE): TE determines the sensitivity to T2*, which varies for different tissues

• Acquisition Time (TA): The time between acquisitions (TR > TE; often TR=TA)

Detecting BOLDDeoxyhaemoglobin is paramagnetic, positive susceptibility:

Changes local susceptibility and therefore T2*

MRI Sequence requirements:• T2* sensitive• fast• whole brain

=> Echo planar imaging (EPI)

Thulborn et al., 1982

MRI Safety

• Powerful magnetic field

• Extreme forces during rapidly changing gradients

• RF energy deposition

• Confined environment / restraints

• Need for controlled access and screening

Paradigm DesignBlock paradigm

…

TR Continuous acquisition…

Event Related

Continuous acquisition……

……

Event Related (compressed)

Paradigm Design

Magnitude of the BOLD effect can be modulated experimentally:

• Task difficulty (set size, encode-retrieve delay, stimulus frequency, stimulus load, distracters…)• Learning (decrease in activation)• Accommodation (decrease in activation)• Other stimulus (pharmaceutical, mood induction, age…)[somatosensory internal standard, on-line behavioural data]

Baseline tasks must be appropriate for cognitive subtraction

Data Analysis

EPI MRI data volumes are continuously acquired whilst the subject performs some cognitive task (paradigm).

Following pre-processing, analysis proceeds as:

1.The within-group activation engendered by the paradigm on average2.The between-group difference in activation or the within-group correlation of activation with some other variable

Data Analysis: summary

(1) Pre-process data from each individual to correct subject motion

(2) Estimate response at each voxel (General linear model)(3) Map subjects into same anatomic space(4) Statistically infer activation for each group(5) Statistically infer difference between groups

Data Analysis of individuals

Subject movement

Response estimation (GLM)

Spatial normalisation

Difference between male/female Europeans

Difference between European/Japanese males

Real time fMRI

Monti et al, 2010

Block paradigmTwo conditions (motor, spatial)Two distinct regions Infer responses

Data Analysis of groups

Within-groupH0: activation is uncorrelated to stimulus

Between-groupH0: zero mean difference between groups (whole brain)

Differences extend outside “activated” network

Resting state fMRI

Deactivations: regions with greater activations in task-absent conditions

Seed-based correlations

“Doing nothing”

Resting state fMRI

(a) anaesthetized macaque; (b) human

End