Class 3: Neurons BOLD

2012 spring fMRI: theory & practice

Stimulus to BOLD

Source: Arthurs & Boniface, 2002, Trends in Neurosciences

BOLD signal

Source: Doug Noll’s primer

Neuron BOLD?

Raichle, 2001, Nature

Vasculature

Source: Menon & Kim, TICS

Figure 6.8 Blood supply to the human cerebrum

Macro- vs. micro- vasculatureMacrovasculature:

vessels > 25 m radius(cortical and pial veins) linear and oriented cause both magnitude and phase changes

Microvasculature:vessels < 25 m radius(venuoles and capillaries) randomly oriented cause only magnitude changes

Capillary beds within the cortex.

Neural Networks

Post-Synaptic Potentials

• The inputs to a neuron (post-synaptic potentials) increase (excitatory PSPs) or decrease (inhibitory PSPs) the membrane voltage

• If the summed PSPs at the axon hillock push the voltage above the threshold, the neuron will fire an action potential

Even Simple Circuits Aren’t Simple

Will BOLD activation from the blue voxel reflect:

• output of the black neuron (action potentials)?

• excitatory input (green synapses)?

• inhibitory input (red synapses)?

• inputs from the same layer (which constitute ~80% of synapses)?

• feedforward projections (from lower-tier areas)?

• feedback projections (from higher-tier areas)?

Lower tier area (e.g., thalamus)

Middle tier area (e.g., V1, primary visual

cortex)

Higher tier area (e.g., V2, secondary

visual cortex)

…

gray matter(dendrites, cell bodies

& synapses)

white matter(axons)

Figure 6.15 The change in diameter of arterioles following sciatic stimulation

Figure 6.16 Change in arteriole dilation as a function of distance from active neurons

Figure 7.12 Relative changes in cerebral blood flow and cerebral blood volume following neuronal activity

BOLD Correlations

Local Field Potentials (LFP)• reflect post-synaptic potentials• similar to what EEG (ERPs) and MEG

measureMulti-Unit Activity (MUA)• reflects action potentials• similar to what most electrophysiology

measures

Logothetis et al. (2001)• combined BOLD fMRI and

electrophysiological recordings • found that BOLD activity is more closely

related to LFPs than MUA

Source: Logothetis et al., 2001, Nature

So there are still a lot to explore !!

Deoxygenated Blood Signal Loss

Oxygenated blood?No signal loss…

Deoxygenated blood?

Signal loss!!!

Images from Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging

Figure 7.4 Changes in oxygenated and deoxygenated hemoglobin following neuronal stimulation

Summary of BOLD signal generation

Figure Source, Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging

(A) under normal conditions, oxygenated hemoglobin (Hb) is converted to deoxygenated hemoglobin at a constant rate within the capillary bed. (B) But when neurons become active, the vascular system supplies more oxygenated hemoglobin than is needed by the neurons, through an over-compensatory increase in blood flow. This results in a decrease in the amount of deoxygenated hemoglobin and a corresponding decrease in the signal loss due to T2* effects, leading to a brighter MR image

Figure 7.11 Schematic representations of the BOLD hemodynamic response

Hemodynamic Response Function

% signal change = (point – baseline)/baselineusually 0.5-3%

initial dip-more focal and potentially a better measure-somewhat elusive so far, not everyone can find it

time to rise signal begins to rise soon after stimulus begins

time to peaksignal peaks 4-6 sec after stimulus begins

post stimulus undershootsignal suppressed after stimulation ends

fMRI Measures the Population Activity• population activity depends on

– how active the neurons are– how many neurons are active

• manipulations that change the activity of many neurons a little have a show bigger activation differences than manipulations that change the activation of a few neurons a lot– attention

• activity– learning

• activity

• fMRI may notmatch single neuronphysiology results

Verb generation Verb generation after 15 min practice

Raichle & Posner, Images of Mind cover imageIdeas from: Scannell & Young, 1999, Proc Biol Sci

Comparing Electrophysiolgy and BOLD

Data Source: Disbrow et al., 2000, PNASFigure Source, Huettel, Song & McCarthy, Functional Magnetic Resonance Imaging

The Concise SummaryWe sort of understand this

(e.g., psychophysics, neurophysiology)

We sort of understand this (MR Physics)We’re *&^%$#@ clueless here!

Bottom Line• Despite all the caveats, questions and concerns, BOLD

imaging is well-correlated with results from other methods

• BOLD imaging can resolve activation at a fairly small scale (e.g., retinotopic mapping)

• PSPs and action potentials are correlated so either way, it’s getting at something meaningful

• even if BOLD activation doesn’t correlate completely with electrophysiology, that doesn’t mean it’s wrong– may be picking up other processing info (e.g., PSPs,

synchrony)

PET vs. fMRI• fMRI does not require exposure to radiation

– fMRI can be repeated

• fMRI has better spatial and temporal resolution– requires less averaging– can resolve brief single events

• MRI is becoming very common; PET is specialized• MRI can obtain anatomical and functional images within same session

• PET can resolve some areas of the brain better• in PET, isotopes can tagged to many possible tracers (e.g., glucose or

dopamine)• PET can provide more direct measures about metabolic processes