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How well do we understand the neural origins of the fMRI BOLD signal?

How well do we understand the neural origins of the fMRI BOLD signal?. Owen J Arthurs and Simon Boniface Trends in Neuroscience, 2002 Gillian Elizabeth Munro, Nov 19, 2002. The Current Paper.

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How well do we understand the neural origins of the fMRI BOLD signal?

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  1. How well do we understand the neural origins of the fMRI BOLD signal? Owen J Arthurs and Simon Boniface Trends in Neuroscience, 2002 Gillian Elizabeth Munro, Nov 19, 2002

  2. The Current Paper • Examines our current understanding of the neural basis of the fMRI BOLD signal, and the ways that this knowledge can be improved

  3. Overview • What is BOLD imaging? • The haemodynamic response • Evoked potentials and local field potentials • Synaptic activity and action potentials • Excitatory and inhibitory activity

  4. What is the fMRI BOLD signal? • Blood oxygenation level-dependant imaging (BOLD) is most common method of fMRI • Relies on the difference in magnetization between oxy- and deoxyhaemoglobin • It is assumed to correlate with neural activity

  5. Haemodynamic Coupling • Link between blood oxygenation levels and neural activity is known as “neurovascular coupling” • Nature of this mechanism is unknown

  6. The haemodynamic response and fMRI BOLD signals Neuronal activity Nurovascular coupling The haemodynamic response Detection by the scanner

  7. Evoked Potentials and Local Field Potentials • The BOLD response directly reflects an increase in neural activity, correlating with local field potentials (LFPs) and evoked potentials • Evoked potentials and LFPs reflect population synaptic activity, NOT neuronal firing rates

  8. Evoked Potentials and Local Field Potentials Cont’d • There is a linear correlation between neuronal activity and the haemodynamic response

  9. Synaptic activity • Action potentials and synaptic activity correlate with BOLD • There is evidence that activity of cortical cells does not substantially contribute to the brain’s metabolic activity • The main determinant of these changes is the re-establishment of ionic concentrations after synaptic activity

  10. Relevance of this relationship • EPSPs and IPSPs influence synaptic firing rate • Thus, one would expect that spiking activity adapts quickly, while LFP activity may be maintained during stimulus presentation • This relationship is difficult to standardize and/or quantify, as it may vary across time and cortical areas

  11. Relevance cont’d • Would expect that there is a linear relationship between action potential firing rate and synaptic metabolic activity • Would also expect a linear correlation between a linear correlation between BOLD and spiking activity, as: • Spiking activity is correlated with firing rates, and firing rates are correlated with the BOLD signal

  12. BOLD and population activity • Unclear whether it can differentiate between small changes in large populations vs large changes in small populations • Also unclear whether takes into account changes in background activity (e.g. attention, cognitive states)

  13. BOLD and attention • Not only are BOLD signals non-absolute, but there is also a variable relationship between action potentials and synaptic energy demand • Changes in attentional states could mask underlying neuronal changes • Thus, the the ability of BOLD to detect stimulus-correlated activity is unpredictable

  14. BOLD and other neuronal events • BOLD has the potential to include other neuronal events: - Bursts - Oscillations - Changes in neuronal synchrony

  15. Problems with global scaling techniques • In eliminating the effect of steady population firing, could lose information regarding changes in cognitive states such as attention and sensory arousal

  16. BOLD and Inhibitory Activity • Inhibitory synaptic activity may modulate BOLD response by changing the metabolic demand, or by inducing net spiking activity • The energy needed to produce an action potential, or to recycle inhibitory neurotransmitters, may cancel out the reduction in activity of inhibited post-synaptic cells

  17. Inhibitory Activity Cont’d • BUT it is unlikely that an area of cortex could sustain a high volume of inhibitory activity, therefore causing a high metabolic and low firing rate • ~ 20% of cells in the cerebral cortex are non-pyramidal inhibitory cells • There could be a lower metabolic demand during inhibition than during excitation

  18. Evidence from cerebellar cells • The principle cells in the cerebellum are inhibitory • In rats, no correlation has been found between blood flow and cellular activity in this region • This could suggest that excitatory activity alone provides basis for BOLD

  19. Does inhibition produce a change in the BOLD signal? • Inhibitory activity may modulate the BOLD signal in a variable way: - increasing it when the prevailing level of excitement is low - decreasing it when the prevailing level of excitement is high

  20. The use of neural drugs such as GABA-mediated inhibitory blockers could shed light on this issue

  21. Conclusion • BOLD signals are related to a number of factors • Evidence supports a correlation between BOLD and population synaptic activity • May also be correlated with cellular action potentials • In need of further investigation, especially regarding the relationship between electrical activity and the BOLD signal

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