Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain

Abstract

The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO2 coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction—independent of details of the model—that if the CBF/CMRO2 coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO2 response (~1.7-fold) compared to the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes.

Improving estimates of the cerebral metabolic rate of oxygen from optical imaging data

“…For example, increasing stimulus intensity is likely to increase both excitatory and inhibitory activity; however, if inhibitory activity has a stronger effect on increasing the CBF response than the CMRO 2 response, then increases in stimulus intensity would lead to increases in the coupling ratio. This hypothesis is consistent with a recent calibrated BOLD study in the visual cortex (Liang et al, 2013). In the case of an extremely strong stimulus, the high level of inhibitory activity could even start to decrease the magnitude of the CMRO 2 response while simultaneously increasing the CBF response.…”

Understanding the dynamic relationship between cerebral blood flow and the BOLD signal: Implications for quantitative functional MRI

“…It similarly merits noting that in a recent investigation into the effect of image contrast on the CBF-CMRO 2 coupling ratio, n , our group found statistically significant differences in the coupling ratios estimated from the BOLD and CBF responses to low and high contrast stimuli, with high contrast stimuli evoking both larger BOLD and CBF responses as well as higher coupling ratios (Liang et al, 2013). This phenomenon has the potential to produce an effect on the CBF-BOLD relationship similar to the one observed in this study, wherein the trajectory of the CBF-BOLD relationship is less concave than predicted by Equation 1.…”

“…Due to the physiological complexity of the signal, however, it is not possible to interpret the BOLD signal as a quantitative reflection of the magnitude of the underlying neural activity, or even the underlying physiological changes in CBF and CMRO 2 . The calibrated BOLD approach has the potential to address the quantitative limitations of BOLD imaging, and in a number of simple experiments, has demonstrated sensitivity to subtleties in the physiological response to neural stimulation that lead to incorrect conclusions when observed through BOLD imaging alone (Ances et al, 2008; Griffeth et al, 2011; Liang et al, 2013). As interest is shifting from using BOLD imaging to map brain regions that respond to simple stimuli to analyzing the complex spatial and temporal characteristics of BOLD signals during unconstrained experiments (Smith et al, 2009; Snyder and Raichle, 2012), it would be useful to be able to employ quantitative imaging techniques under more dynamic conditions.…”

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

“…The ratio of the CBF and CMRO 2 responses is known as the coupling parameter, n =%ΔCBF/%ΔCMRO 2 . Recent findings from our group and others suggest that not only do CBF and CMRO 2 change to different degrees, but their coupling in the brain is not constant depending instead both on the baseline state of the brain (Brown, Eyler Zorrilla et al 2003, Perthen, Lansing et al 2008, Griffeth, Perthen et al 2011) and the stimulus (Lin, Fox et al 2010, Moradi, Buracas et al 2012, Liang, Ances et al 2013, Moradi and Buxton 2013). These divergent responses suggest that, although they change in parallel, they are actually driven by separate mechanisms.…”