Most functional brain imaging studies use task-induced hemodynamic responses to infer underlying changes in neuronal activity. In addition to increases in cerebral blood flow and blood oxygenation level-dependent (BOLD) signals, sustained negative responses are pervasive in functional imaging. The origin of negative responses and their relationship to neural activity remain poorly understood. Through simultaneous functional magnetic resonance imaging and electrophysiological recording, we demonstrate a negative BOLD response (NBR) beyond the stimulated regions of visual cortex, associated with local decreases in neuronal activity below spontaneous activity, detected 7.15 +/- 3.14 mm away from the closest positively responding region in V1. Trial-by-trial amplitude fluctuations revealed tight coupling between the NBR and neuronal activity decreases. The NBR was associated with comparable decreases in local field potentials and multiunit activity. Our findings indicate that a significant component of the NBR originates in neuronal activity decreases.

Recent studies have demonstrated large amplitude spontaneous fluctuations in functional-MRI (fMRI) signals in humans in the resting state. Importantly, these spontaneous fluctuations in blood-oxygenation-level-dependent (BOLD) signal are often synchronized over distant parts of the brain, a phenomenon termed functional-connectivity. Functional-connectivity is widely assumed to reflect interregional coherence of fluctuations in activity of the underlying neuronal networks. Despite the large body of human imaging literature on spontaneous activity and functional-connectivity in the resting state, the link to underlying neural activity remains tenuous. Through simultaneous fMRI and intracortical neurophysiological recording, we demonstrate correlation between slow fluctuations in BOLD signals and concurrent fluctuations in the underlying locally measured neuronal activity. This correlation varied with time-lag of BOLD relative to neuronal activity, resembling a traditional hemodynamic response function with peaks at approximately 6 s lag of BOLD signal. The correlations were reliably detected when the neuronal signal consisted of either the spiking rate of a small group of neurons, or relative power changes in the multi-unit activity band, and particularly in the local field potential gamma band. Analysis of correlation between the voxel-by-voxel fMRI time-series and the neuronal activity measured within one cortical site showed patterns of correlation that slowly traversed cortex. BOLD fluctuations in widespread areas in visual cortex of both hemispheres were significantly correlated with neuronal activity from a single recording site in V1. To the extent that our V1 findings can be generalized to other cortical areas, fMRI-based functional-connectivity between remote regions in the resting state can be linked to synchronization of slow fluctuations in the underlying neuronal signals.

Most fMRI studies are based on the detection of a positive BOLD response (PBR). Here, we demonstrate and characterize a robust sustained negative BOLD response (NBR) in the human occipital cortex, triggered by stimulating part of the visual field. The NBR was spatially adjacent to but segregated from the PBR. It depended on the stimulus and thus on the pattern of neuronal activity. The time courses of the NBR and PBR were similar, and their amplitudes covaried both with increasing stimulus duration and increasing stimulus contrast. The NBR was associated with reductions in blood flow and with decreases in oxygen consumption. Our findings support the contribution to the NBR of (1) a significant component of reduction in neuronal activity and (2) possibly a component of hemodynamic changes independent of the local changes in neuronal activity.