Total neuroenergetics support localized brain activity: implications for the interpretation of fMRI

Abstract

In alpha-chloralose-anesthetized rats, changes in the blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal (DeltaS/S), and the relative spiking frequency of a neuronal ensemble (Deltanu/nu) were measured in the somatosensory cortex during forepaw stimulation from two different baselines. Changes in cerebral oxygen consumption (DeltaCMR(O2)/CMR(O2)) were derived from the BOLD signal (at 7T) by independent determinations in cerebral blood flow (DeltaCBF/CBF) and volume (DeltaCBV/CBV). The spiking frequency was measured by extracellular recordings in layer 4. Changes in all three parameters (CMR(O2), nu, and S) were greater from the lower baseline (i.e., deeper anesthesia). For both baselines, DeltaCMR(O2)/CMR(O2) and Deltanu/nu were approximately one order of magnitude larger than DeltaS/S. The final values of CMR(O2) and nu reached during stimulation were approximately the same from both baselines. If only increments were required to support functions then their magnitudes should be independent of the baseline. In contrast, if particular magnitudes of activity were required, then sizes of increments should inversely correlate with the baseline (being larger from a lower baseline). The results show that particular magnitudes of activity support neural function. The disregard of baseline activity in fMRI experiments by differencing removes a large and necessary component of the total activity. Implications of these results for understanding brain function and fMRI experiments are discussed.

Fig 1.

The changes in energy metabolism (CMR_O2, n = 6) and relative spiking frequency (ν, n = 36) during forepaw stimulation in α-chloralose anesthetized rats. (A and B) Relative changes in CMR_O2 (A) and ν (B) during stimulation in conditions I and II, which are shown in gray and black, respectively. The stimulus duration is shown with the black bar (see Table 1).

Fig 2.

The changes in CMR_O2 and ν relative to the baseline in condition I. Although the increments (filled) of CMR_O2 and ν were different in conditions I (gray) and II (black), the same activity level was reached on stimulation where the size of the increment depended on the baseline level (open). The dotted arrows represent the projected baseline value of CMR_O2 in the resting awake condition (ref. ; see Table 2).

Fig 3.

Changes in relative spiking frequency (Δν/ν) in relation to changes in the BOLD signal (ΔS/S). The origin is with respect to the baseline in condition I. The final levels reached on stimulation from both baseline conditions are approximately similar, but as shown in Table 1 that while Δν/ν ≈ ΔCMR_O2/CMR_O2 (within experimental errors) and Δν/ν ≫ ΔS/S over the wide range of activities measured.