Ultra-High Field ³¹ P functional Magnetic Resonance Spectroscopy Reveals NAD ⁺ Dynamics in Brain Energy Metabolism during Visual Stimulation

We investigated dynamic changes in nicotinamide adenine dinucleotide (NAD□) metabolism in the human occipital lobe using ultra-high field 31P functional magnetic resonance spectroscopy (fMRS) at 7 Tesla. Twenty-five healthy volunteers (mean age 24 ± 4 years, 10 female) performed a visual task alternating between fixation and flashing checkerboard stimuli. 31P MRS spectra were acquired from a visual cortex voxel functionally localized by prior fMRI. Linear mixed-effects modelling revealed a significant reduction in NAD□ concentrations during the first stimulation block, while no significant change was observed during the second block. No significant changes were observed for other high-energy phosphate metabolites (ATP, phosphocreatine, and inorganic phosphate), indicating specificity in the NAD□ response. Exploratory analyses, dividing the blocks in two halves, suggested further reductions in NAD□ and tNAD in the second halves of both stimulation blocks, though these trends were not statistically significant. Our findings demonstrate the feasibility of using fMRS at 7T to detect stimulus-induced dynamics in cerebral NAD□ metabolism in vivo, providing insights into the interplay between glycolysis and oxidative phosphorylation during neural activation.