Metabolic Origin of Bold Signal Fluctuations in the Absence of Stimuli

Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging studies have shown the existence of ongoing blood flow fluctuations in the absence of stimuli. Although this so-called ‘resting-state activity’ appears to be correlated across brain regions with apparent functional relationship, its origin might be predominantly vascular and not directly representing neuronal signaling. To investigate this, we simultaneously measured BOLD and perfusion signals on healthy human subjects ( n = 11) and used their ratio (BOLD/perfusion ratio or BPR) as an indicator of metabolic demand. BPR during rest and sleep was compared with that during a visual task (VT) and a breath-holding task (BH), which are challenges with substantial and little metabolic involvement, respectively. Within the visual cortex, BPR was 3.76 ± 1.23 during BH, which was significantly higher than during the VT (1.76 ± 0.27) and rest (1.56 ± 0.41). Meanwhile, BPR values during VT and rest were not significantly different, suggesting a similar metabolic involvement. Eight subjects showed stage 1 and 2 sleep, during which temporally correlated BOLD and perfusion activity continued. In these subjects, there was no significant difference in BPR between the sleep and waking conditions (1.79 ± 0.54 and 1.66 ± 0.67, respectively), but both were lower than the BPR during BH. These data suggest that resting-state activity, at least in part, represents a metabolic process.