Neurophysiology of the BOLD fMRI signal in awake monkeys

Background: Simultaneous intracortical recordings of neural activity and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in primary visual cortex of anesthetized monkeys demonstrated varying degrees of correlation between fMRI signals and the different types of neural activity, such as local field potentials (LFPs), multiple-unit activity (MUA), and single-unit activity (SUA). One important question raised by the aforementioned investigation is whether the reported correlations also apply to alert subjects. Results: Monkeys were trained to perform a fixation task while stimuli within the receptive field of each recording site were used to elicit neural responses followed by a BOLD response. We show - also in alert behaving monkeys - that although both LFP and MUA make significant contributions to the BOLD response, LFPs are better and more reliable predictors of the BOLD signal. Moreover, when MUA responses adapt but LFP remains unaffected, the BOLD signal remains unaltered. Conclusions: The persistent coupling of the BOLD signal to the field potential when LFP and MUA have different time evolutions suggests that BOLD is primarily determined by the local processing of inputs in a given cortical area. In the alert animal the largest portion of the BOLD signal's variance is explained by an LFP range (20-60 Hz) that is most likely related to neuromodulation. Finally, the similarity of the results in alert and anesthetized subjects indicates that at least in V1 anesthesia is not a confounding factor. This enables the comparison of human fMRI results with a plethora of electrophysiological results obtained in alert or anesthetized animals.