The Basics of f MRI Overview Physiological origins

The Basics of f. MRI Overview: • Physiological origins (BOLD) • Physical origins (MRI) • Physical measurements of BOLD • Paradigm (task) design • Analysis of task-activated f. MRI • Resting f. MRI

Physiological origins stimulus Change in oxy: deoxy ratio Neurophysiological coupling: neuronal activity blood oxygenation Logothetis et al. (2001) Nature 412: 150 LFP – local field potentials MUA – multi unit activity SDF – spike density function

Physiological origins Local 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 O 2 extraction ‘hence’ oversupply of blood • Haemodynamic response function (HRF)

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

Physical origins Amplitude of signal determined by: • Proton density: more protons, more signal • T 1 (spin-lattice relaxation): Stimulated by local magnetic field fluctuations due to magnetic properties of other molecules. • T 2*: Enhanced dephasing due to inhomogeneities in local magnetic field (inc. B 0) – susceptibility. • T 2 (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 T 2*, which varies for different tissues • Acquisition Time (TA): The time between acquisitions (TR > TE; often TR=TA)

Detecting BOLD Deoxyhaemoglobin is paramagnetic, positive susceptibility: Changes local susceptibility and therefore T 2* MRI Sequence requirements: • T 2* 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 Design Block paradigm TR Event Related Continuous acquisition … … 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 average 2. 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 Response estimation (GLM) Difference between European/Japanese males Difference between male/female Europeans Subject movement Spatial normalisation

Real time f. MRI Block paradigm Two conditions (motor, spatial) Two distinct regions Infer responses Monti et al, 2010

Data Analysis of groups Differences extend outside “activated” network Within-group H 0: activation is uncorrelated to stimulus Between-group H 0: zero mean difference between groups (whole brain)

Resting state f. MRI “Doing nothing” Seed-based correlations Deactivations: regions with greater activations in task-absent conditions

Resting state f. MRI (a) anaesthetized macaque; (b) human

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