Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms. Journal of Cerebral Blood INTRODUCTIONFunctional magnetic resonance spectroscopy (fMRS) is a powerful tool that allows quantifying the dynamic of brain metabolite concentrations in the working brain in vivo. Different laboratories have recently used fMRS at ultra-high magnetic field (7 Tesla (7 T)) to measure the neurochemical responses occurring during stimulation of the human visual cortex. [1][2][3][4] The results of these studies were highly consistent with concentration changes in the order of 0.2 μmol/g being reported for aspartate (Asp), glutamate (Glu), glucose (Glc), and lactate (Lac) during prolonged visual stimuli. Similar changes of Glu and Lac have also been reported in the motor cortex. 5 The observed functional changes of metabolite concentrations support an overall increase in oxidative energy metabolism during neuronal activation. 6 In particular, the opposite changes in Glc and Lac concentrations are thought to reflect increased metabolic rate of Glc utilization and activation of the aerobic glycolytic pathway in brain cells. [7][8][9] The observed decrease in Asp and increase in Glu have been interpreted as a consequence of an increased rate of the malate-aspartate shuttle, which is associated with the increased flux into the tricarboxylic acid (TCA) cycle.

This study indicates that disconnection precedes GM atrophy in the PCC, which is a critical area of the DMN, and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflects a long term effect of brain disconnection. In this context, our study indicates that GM atrophy in PCC accompanies the conversion from MCI to AD.

Proton magnetic resonance spectroscopy ( 1 H-MRS) has been used in a number of studies to noninvasively assess the temporal changes of lactate in the activated human brain. However, the results have not been consistent. The aim of the present study was to test the sensitivity of 1 H-MRS during functional experiments at the highest magnetic field currently available for human studies (7 T). Stability and reproducibility of the measurements were evaluated from LCModel analysis of time series of spectra measured during a visual stimulation paradigm and by examination of the difference between spectra obtained at rest and during activation. The sensitivity threshold to detect concentration changes was 0.2 Amol/g for most of the quantified metabolites. The possible variations of metabolite concentrations during visual stimulation were within the same range (F0.2 Amol/g). In addition, the influence of a small line-narrowing effect due to the blood oxygenation leveldependent (BOLD) T2* changes on the estimated concentrations was simulated. Quantification of metabolites was, in general, not affected beyond 1% by line-width changes within 0.5 Hz.

Unraveling the energy metabolism and the hemodynamic outcomes of excitatory and inhibitory neuronal activity is critical not only for our basic understanding of overall brain function, but also for the understanding of many brain disorders. Methodologies of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are powerful tools for the non-invasive investigation of brain metabolism and physiology. However, the temporal and spatial resolution of in vivo MRS and MRI is not suitable to provide direct evidence for hypotheses that involve metabolic compartmentalization between different cell types, or to untangle the complex neuronal micro-circuitry which results in changes of electrical activity. This review aims at describing how the current models of brain metabolism, mainly built on the basis of in vitro evidence, relate to experimental findings recently obtained in vivo by 1H MRS, 13C MRS and MRI. The hypotheses related to the role of different metabolic substrates, the metabolic neuron-glia interactions, along with the available theoretical predictions of the energy budget of neurotransmission, will be discussed. In addition, the cellular and network mechanisms that characterize different types of increased and suppressed neuronal activity will be considered within the sensitivity-constraints of MRS and MRI.