Abstract
Functional magnetic resonance imaging (fMRI) techniques in which the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) response to a neural stimulus are measured, can be used to estimate the fractional increase in the cerebral metabolic rate of oxygen consumption (CMRO2) that accompanies evoked neural activity. A measure of neurovascular coupling is obtained from the ratio of fractional CBF and CMRO2 responses, defined as n, with the implicit assumption that relative rather than absolute changes in CBF and CMRO2 adequately characterise the flow-metabolism response to neural activity. The coupling parameter n is important in terms of its effect on the BOLD response, and as potential insight into the flow-metabolism relationship in both normal and pathological brain function. In 10 healthy human subjects, BOLD and CBF responses were measured to test the effect of baseline perfusion (modulated by a hypercapnia challenge) on the coupling parameter n during graded visual stimulation. A dual-echo pulsed arterial spin labelling (PASL) sequence provided absolute quantification of CBF in baseline and active states as well as relative BOLD signal changes, which were used to estimate CMRO2 responses to the graded visual stimulus. The absolute CBF response to the visual stimuli were constant across different baseline CBF levels, meaning the fractional CBF responses were reduced at the hyperperfused baseline state. For the graded visual stimuli, values of n were significantly reduced during hypercapnia induced hyperperfusion. Assuming the evoked neural responses to the visual stimuli are the same for both baseline CBF states, this result has implications for fMRI studies that aim to measure neurovascular coupling using relative changes in CBF. The coupling parameter n is sensitive to baseline CBF, which would confound its interpretation in fMRI studies where there may be significant differences in baseline perfusion between groups. The absolute change in CBF, as opposed to the change relative to baseline, may more closely match the underlying increase in neural activity in response to a stimulus.
Highlights
Functional magnetic resonance imaging based on the blood oxygenation level dependent (BOLD) effect is a useful tool for spatially mapping stimulus induced neural activity in the human brain
Further work to characterise the dynamic range of n for a graded stimulus across multiple baseline perfusion levels is needed, as it could potentially provide a marker of cerebrovascular health
We show that ΔCBF is independent of CBF0 and conceivably more representative of neurovascular coupling than %ΔCBF
Summary
Functional magnetic resonance imaging (fMRI) based on the blood oxygenation level dependent (BOLD) effect is a useful tool for spatially mapping stimulus induced neural activity in the human brain. The fundamental physiological phenomenon producing the BOLD response is a divergence in CBF and CMRO2 changes, first observed in PET (Fox and Raichle, 1986), which results in a paradoxical increase in blood oxygenation downstream from the site of increased neural activity and causing an increase in the measured local MR signal. The haemodynamic nature of the BOLD signal permits only a qualitative estimate of neural activity, which makes interpretation and group level comparisons difficult. The nonspecific nature of signal changes is problematic for studies of patient populations, where pathological or atypical cerebral physiology may confound interpretation of the BOLD signal as a surrogate measure of evoked neural activity
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