BOLD response during uncoupling of neuronal activity and CBF.

The widely used technique of functional magnetic resonance imaging (fMRI) based on the blood oxygenation level-dependent (BOLD) effect is a tool for the investigation of changes in local brain activity upon stimulation. The principle of measurement is based on the assumption that there is a strong coupling between changes in neural activity, metabolism, vascular response and oxygen extraction in the area under investigation. As fMRI is on the way to become a routine tool in clinical examinations, we wanted to investigate whether, generally and under a variety of conditions, there is a strong link between the BOLD signal and neural activity. For clinical and experimental application of the method, it is crucial, whether the absence of changes in BOLD signal intensity upon stimulation can always be interpreted as an absence of changes in brain activity. We approached this question by inhibiting the nitric oxide mediated 'neurovascular coupling' via application of 7 nitroindazole. Before and after inhibition of this neurovascular coupling, we acquired evoked potentials and performed fMRI during somatosensory stimulation in rats. Cerebral blood flow response as well as BOLD signal intensity changes following electrical stimulation were abolished within 10 min after application of 7 nitroindazole, whereas somatosensory-evoked potentials were only slightly affected but still clearly detectable. Even 1 h after injection of 7 nitroindazole, there was still remaining electrical activity. Thus, we observed an uncoupling between electrical, i.e., neural activity and the BOLD signal. According to our results, the absence of BOLD signal changes did not permit the conclusion that there was no neural activity in the area under investigation. Our findings are especially relevant for the clinical application of fMRI in patients suffering from cerebrovascular and other brain diseases.