The coupling of cerebral blood flow and oxygen metabolism with brain activation is similar for simple and complex stimuli in human primary visual cortex

Abstract

Quantitative functional MRI (fMRI) experiments to measure blood flow and oxygen metabolism coupling in the brain typically rely on simple repetitive stimuli. Here we compared such stimuli with a more naturalistic stimulus. Previous work on the primary visual cortex showed that direct attentional modulation evokes a blood flow (CBF) response with a relatively large oxygen metabolism (CMRO2) response in comparison to an unattended stimulus, which evokes a much smaller metabolic response relative to the flow response. We hypothesized that a similar effect would be associated with a more engaging stimulus, and tested this by measuring the primary human visual cortex response to two contrast levels of a radial flickering checkerboard in comparison to the response to free viewing of brief movie clips. We did not find a significant difference in the blood flow-metabolism coupling (n=%ΔCBF/%ΔCMRO2) between the movie stimulus and the flickering checkerboards employing two different analysis methods: a standard analysis using the Davis model and a new analysis using a heuristic model dependent only on measured quantities. This finding suggests that in the primary visual cortex a naturalistic stimulus (in comparison to a simple repetitive stimulus) is either not sufficient to provoke a change in flow-metabolism coupling by attentional modulation as hypothesized, that the experimental design disrupted the cognitive processes underlying the response to a more natural stimulus, or that the technique used is not sensitive enough to detect a small difference.

Keywords: Blood flow–oxygen metabolism coupling; Calibrated BOLD; Cerebral blood flow (CBF); Cerebral metabolic rate of oxygen (CMRO(2)); Functional MRI; Visual cortex.

Figure 1. Average fractional changes in BOLD and CBF in response to for 10% contrast (blue), 40% contrast (red) and movie stimulus (green)

Evoked responses and undershoots are considered relative to the mean baseline preceding the stimulus. The BOLD (a) and CBF (b) stimulus responses and undershoots for each stimulus type are displayed.

Figure 2. Measured BOLD and calculated CMRO₂ plotted against CBF for the three stimulus types

Crossbars on the data points represent standard error of the mean for CBF (horizontal) and either BOLD or CMRO₂(vertical). (a) Average BOLD and CBF data are plotted for the three stimulus types. (b) Again using the optimized Davis model, CMRO₂ responses were calculated. Lines for n are plotted using the optimized Davis model with M=11.6, α=0.13 and β=0.92. The data for the three stimulus types are not significantly different: 10% contrast (n=2.79, vs. 40% p=0.65), 40% contrast (n=2.39, vs. movie p=0.42) and movie stimulus (n=2.46, vs. 10% p=0.87).

Figure 3. Ratio method for comparison of CBF-CMRO₂ coupling

In this figure the subscripted ‘x’ corresponds to the test state (either 10% contrast or movie stimulus) while ‘ref’ corresponds to the reference state (40% contrast). The star in each figure represents the case in which the BOLD and CBF responses to the test state and reference state are the same. The dashed black equality line represents the null hypothesis that n is the same between the two states; data points fall above the line when the test state has a higher n than the reference and below the line when the test state has a lower n. (a) Comparison of the average BOLD and non-linear CBF ratios. Error bars represent the standard error of the mean. (b) Comparison of the individual subject BOLD and non-linear CBF ratios. Using the ratio method no difference was found between the CBF-CMRO₂ coupling of the 40% contrast checkerboards in comparison to either the movie stimulus or 10% contrast checkerboards.