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.

] Department of Radiology Center for Magnetic Resonance Research University of Minnesota Minneapolis Minnesota USA [2] Division of Endocrinology Department of Medicine University of Minnesota Minneapolis Minnesota USA [3] Multimodal and Functional Neuroimaging Research Group CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

] MARBILab Museo storico della fisica e Centro di studi e ricerche Enrico Fermi Rome Italy [2] Fondazione Santa Lucia IRCCS Rome Italy

Department of Radiology Center for Magnetic Resonance Research University of Minnesota Minneapolis Minnesota USA

Division of Biostatistics School of Public Health University of Minnesota Minneapolis Minnesota USA

FMRIB Centre University of Oxford Oxford UK

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