BOLD???

1. BOLD???

2. Material • SPM Courses and Slides http://www.fil.ion.ucl.ac.uk/spm/course/ Kerstin Preuschoff: “Physiological Basis of the BOLD signal” • Jody Culham – fMRI 4 Newbies http://psychology.uwo.ca/fmri4newbies/ “ fMRI Physics and BOLD”

3. fMRI uses sequences that are sensitive to T2* Transversal Relaxation 2 factors cause signal decay 1 1. protons “bump” into other molecules (tissue specific) 1+2 2. magnetic field is uneven (spatial inhomogeneities of magnetic field) e.g. where brain meets air/bone

4. sinuses ear canals Susceptibility Artifacts T1-weighted image T2*-weighted image • -In T2* images, artefactsoccur near junctions between air and tissue • sinuses, ear canals • In some ways this sucks, but in one way, it’s fabulous… From fMRI 4 NEWBIES, Jodie Culham

5. fMRI uses sequences that are sensitive to T2* Transversal Relaxation 2 factors cause signal decay 1 1. protons “bump” into other molecules (tissue specific) 1+2 2. magnetic field is uneven (spatial inhomogeneities of magnetic field) e.g. Where brain meets air/bone Where there is deoxygenated blood Imaging Method for fMRI EPI (echo planar imaging) -1 excitation pulse, rapid (40-100 ms)

6. Oxygenated blood > no signal loss High oxygenated\ deoxygenated blood ratio > signal decay slower Low oxygenated\ deoxygenated blood ratio > signal decay faster (=dark) Deoxygenated blood > signal loss Images from Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging From fMRI 4 NEWBIES, Jodie Culham and Kerstin Preuschoff (SPM course)

7. Hemoglobin Figure Source, Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging From fMRI 4 NEWBIES, Jodie Culham

8. Short summary • functional MRI measures haemodynamic changes • Haemodynamic changes measured are changes in the local ratio between deoxygenated and oxygenated blood • BOLD = Blood Oxygenation Level Dependent

9. From Kerstin Preuschoff (SPM course)

10. fMRI measures heamodynamic changes fMRI does not measure directly changes in brain activation and metabolism What do we actually measure?

11. Stimulus to BOLD??? -Blood flow seems to be controlled by postsynaptic processes leading to release of vasodilators Source: Arthurs & Boniface, 2002, Trends in Neurosciences

12. Logothetis (2008): Critical factors determining the utility of fMRI for drawing conclusions in brain research: -spatial and temporal specificity -signal specificity -design

13. -spatial specificity: Biological limits: density & architecture of vasculature (inter-capillary mesh size ca. 50 µm in cortex)

14. Vasculature Source: Menon & Kim, TICS From fMRI 4 NEWBIES, Jodie Culham

15. Source: Logothetis (2008)

16. -spatial specificity: Biological limits: density & architecture of vasculature (inter-capillary mesh size ca. 50 µm in cortex) Problem of mislocalisation of activation near large vessels (mainly a problem when working with high-resolution) Increases with increasing field strength Depends on MR-pulse sequence employed voxel – single volume element, has a resolution: possible 0.5 mm x 0.5 mm x 0.5 mm (humans, whole-head) 300 top-cited cognitive fMRI studies 9-12 mm x 9-12 mm x 5-7 mm

17. -temporal specificity: Technical limits: sampling rate of volumes with multiple slices: 1-3 seconds, can also just acquire a limited number of slices

18. Biological limits: BOLD Time Course 4s -6s changes in MRI intensity 1-10%

19. -signal specificity:

20. Stimulus to BOLD??? -Blood flow seems to be controlled by postsynaptic processes leading to release of vasodilators Source: Arthurs & Boniface, 2002, Trends in Neurosciences

21. Excitation-Inhibition networks (EIN) -final response of each neuron is determined by processes in whole networks -possible dissociation between spiking/output and actual network activity -inhibition adds complexity: increase/decrease of net neural activity/BOLD??? Complex relationship neural network activity and stimulus (including context) processing

22. Stimulus to BOLD??? -Blood flow seems to be controlled by postsynaptic processes leading to release of vasodilators Source: Arthurs & Boniface, 2002, Trends in Neurosciences

23. BOLD Correlations Local Field Potentials (LFP) • reflect peri-synaptic activity • similar to what EEG (ERPs) and MEG measure Multi-Unit Activity (MUA) • reflects action potentials (AP) • similar to what most electrophysiology measures Logothetis et al. (2001) • combined BOLD fMRI and electrophysiological recordings • found thatBOLD activity is more closely related to LFPs than MUA • demonstrated BOLD signal without APs Source: Logothetis et al., 2001, Nature From fMRI 4 NEWBIES, Jodie Culham

24. Local Field Potentials? Postsynaptic Potentials: -reflect local peri-synaptic activity (postsynaptic potentials, also other processes e.g. after-potentials) -temporally and spatially summed net activity -population activity (rather than firing rates) -related to input/processing rather than output (APs) -depends on neural architecture -similar to what EEG (ERPs) and MEG measure Image from fMRI 4 NEWBIES, Jodie Culham

25. Summary: What can we do with fMRI? • Study the brain non-invasively in humans • Make inferences about large neuronal populations/networks/mass action • Look at processing that is summated to some extent over space and time (great resolution compared to other non-invasive methods in humans) • Seems good to study architectural/processing units and functional integration, functioning of a distributed large-scale system and neuromodulation(which is diffuse and slow and “thought to underlie altered states of cognitive capacities such as motivation, attention, learning and memory” Logothetis, 2008) • Excellent tool to formulate intelligent data-based hypotheses regarding brain function that can be further tested in multimodal approach

26. Summary: What can we cannot do with fMRI? • Read minds • Study responses of single neurons • “...cannot easily differentiate between function-specific processing and neuromodulation, bottom-up and top-down signals and may potentially confuse excitation and inhibition” (Logothetis, 2008) • Cannot in most cases test unambiguously hypotheses regarding brain function