Limitations to BOLD

Question 1

Limitations

Answer 1

• From the BOLD signal we cannot always predict changes in CBF, CBV, CMRO2 – especially in pathology when these relations may be abnormal
• Negative BOLD is not always the inverse of positive BOLD and is still an active area of research
• We do not know how different neural processes, e.g. excitation/inhibition, feedforward/feedback, neuromodulation, or different types of neurons (e.g. pyramidal neurons/interneurons), affect the BOLD signal
• Layer-specific BOLD signals

Question 2

Laminar fMRI

Answer 2

• Measuring brain responses specific to separate cortical layers
• Important opportunity to dissociate between feedforward and feedback brain responses
• To isolate layer-specific feedback responses
• Functional imaging of human cortical layers

Question 3

What is the BOLD signal?

Answer 3

• Increase in energy demand by active neurons  local increase in blood flow is required to supply the extra glucose and oxygen required -> achieved through neurovascular coupling
• BOLD contrast is dependent on the level of deoxyhaemoglobin in the blood -> iron in dHb is paramagnetic, this causes inhomogeneities in the magnetic field which decreases the MR signal
• Neurovascular signals increase blood flow and volume, bringing more oxygenated blood and washing out dHb -> net decrease in dHb – resulting in an increased BOLD signal
• BOLD represents the sum of the effects of oxygen consumption (decreasing) and blood flow increase (increasing)

Question 4

What do we know about BOLD?

Answer 4

1. An increase in the positive BOLD signal in adults generally represents a net increase in neuronal activity
2. Neurovascular coupling usually links neuronal activity to increases in blood vessel diameter
3. BOLD is a better indicator of processing within an area than the output of the area - reflects synaptic activity
4. BOLD can be used to glean robust information about functional localization within the brain
5. Early BOLD signals are more reliable reporters of neuronal activity than are late BOLD signals

Question 5

how does our incomplete understanding limit the interpretation of BOLD?

Answer 5

• Properties of neurovascular coupling vary across brain areas, developmental stages and experimental conditions
• Many enzymes are developmentally regulated, and neuronal activity elicits vascular constriction, and CBF decreases – corresponding to negative BOLD responses in infants
• Mechanisms of underlying neurovascular coupling will vary depending on expression patterns of key enzymes and receptors across different brain areas, as well as the local and global circuit dynamics engaged by a given task
• Regional differences in BOLD signal magnitude

Question 6

Future implications

Answer 6

• physiological research on the properties of neurovascular coupling – responsible cell types and neurotransmitters, how these differ across brain regions
• when does BOLD or does not provide useful information about underlying neuronal activity?