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Recent studies from our group and others using quantitative fMRI methods have found that variations of the coupling ratio of blood flow (CBF) and oxygen metabolism (CMRO 2 ) responses to a stimulus have a strong effect on the BOLD response. Across a number of studies an empirical pattern is emerging in the way CBF and CMRO 2  changes are coupled to neural activation: if the stimulus is modulated to create a stronger response (e.g., increasing stimulus contrast), CBF is modulated more than CMRO 2 ; on the other hand, if the brain state is altered such that the response to the same stimulus is increased (e.g., modulating attention, adaptation, or excitability), CMRO 2  is modulated more than CBF. Because CBF and CMRO 2  changes conflict in producing BOLD signal changes, this finding has an important implication for conventional BOLD-fMRI studies: the BOLD response exaggerates the effects of stimulus variation but is only weakly sensitive to modulations of the brain state that alter the response to a standard stimulus. A speculative hypothesis is that variability of the coupling ratio of the CBF and CMRO 2  responses reflects different proportions of inhibitory and excitatory evoked activity, potentially providing a new window on neural activity in the human brain.

frontiers in neuroscience

Variability of the coupling of blood flow and oxygen metabolism responses in the brain: a problem for interpreting BOLD studies but potentially a new window on the underlying neural activity