Origin of negative blood oxygenation level-dependent fMRI signals

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the positive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.