Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI

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Abstract
Functional MRI (fMRI) is widely assumed to measure neuronal activity, but no satisfactory mechanism for this linkage has been identified. Here we derived the changes in the energetic component from the blood oxygenation level-dependent (BOLD) fMRI signal and related it to changes in the neuronal spiking frequency in the activated voxels. Extracellular recordings were used to measure changes in cerebral spiking frequency (Δν/ν) of a neuronal ensemble during forepaw stimulation in the α-chloralose anesthetized rat. Under the same conditions localized changes in brain energy metabolism (ΔCMRO2/CMRO2) were obtained from BOLD fMRI data in conjunction with measured changes in cerebral blood flow (ΔCBF/CBF), cerebral blood volume (ΔCBV/CBV), and transverse relaxation rates of tissue water (T and T2) by MRI methods at 7T. On stimulation from two different depths of anesthesia ΔCMRO2/CMRO2 ≈ Δν/ν. Previous 13C magnetic resonance spectroscopy studies, under similar conditions, had shown that ΔCMRO2/CMRO2 was proportional to changes in glutamatergic neurotransmitter flux (ΔVcyc/Vcyc). These combined results show that ΔCMRO2/CMRO2 ≈ ΔVcyc/Vcyc ≈ Δν/ν, thereby relating the energetic basis of brain activity to neuronal spiking frequency and neurotransmitter flux. Because ΔCMRO2/CMRO2 had the same high spatial and temporal resolutions of the fMRI signal, these results show how BOLD imaging, when converted to ΔCMRO2/CMRO2, responds to localized changes in neuronal spike frequency.