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by claude@2026-07, 2026-07-04
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This study used ultra-high field 7 Tesla ^31P functional magnetic resonance spectroscopy to examine dynamic changes in nicotinamide adenine dinucleotide (NAD^+) metabolism in the occipital lobe of 25 healthy volunteers during a visual checkerboard task, with a voxel functionally localized by prior fMRI. Using linear mixed-effects modeling, the authors found a significant reduction in NAD^+ concentrations during the first stimulation block, with no significant NAD^+ change during the second block, while ATP, phosphocreatine, and inorganic phosphate showed no significant stimulation-related changes. Exploratory split-block analyses suggested further, non-significant reductions in NAD^+ and total NAD in later halves of both blocks. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
ABSTRACT We investigated dynamic changes in nicotinamide adenine dinucleotide (NAD□) metabolism in the human occipital lobe using ultra-high field 31 P 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. 31 P 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.
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ABSTRACT
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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
This revised version incorporates clarifications and additional analyses following peer review.
ABBREVIATIONS
- AMPK
- AMP-activated Protein Kinase
- ATP
- Adenosine Triphosphate
- CBF
- Cerebral Blood Flow
- CMRglc
- Cerebral Metabolic Rate of Glucose
- CMRO2
- Cerebral Metabolic Rate of Oxygen
- COPE
- Contrast of Parameter Estimates
- CRLB
- Cramer-Rao Lower Bound
- cAMP
- Cyclic Adenosine Monophosphate
- ETC
- Electron Transport Chain
- FID
- Free Induction Decay
- FID-A
- FID Appliance
- FLIRT
- FMRIB’s Linear Image Registration Tool
- FSL
- FMRIB Software Library
- FWHM
- Full Width at Half Maximum
- GPC
- Glycerophosphocholine
- GPE
- Glycerophosphoethanolamine
- GSG
- Glucose Sparing by Glycogenolysis
- LCModel
- Linear Combination of Model spectra
- MAS
- Malate-Aspartate Shuttle
- MP-PCA
- Marchenko-Pastur Principal Component Analysis
- MRI
- Magnetic Resonance Imaging
- NAD+
- Nicotinamide adenine dinucleotide (oxidized form)
- NADH
- Nicotinamide adenine dinucleotide (reduced form)
- NADH+
- Nicotinamide adenine dinucleotide (reduced form) with contributions of UDPG
- OGI
- Oxygen-Glucose Index
- OxPhos
- Oxidative Phosphorylation
- PC
- Phosphocholine
- PCr
- Phosphocreatine
- PE
- Phosphoethanolamine
- Piint
- Intracellular Inorganic Phosphate
- Pextt
- Extracellular Inorganic Phosphate
- SNR
- Signal to Noise Ratio
- TCA
- Tricarboxylic Acid Cycle
- tNAD
- Total NAD (NAD+ plus NADH+)
- UPDG
- Uridine Diphosphoglucose
- fMRS
- Functional Magnetic Resonance Spectroscopy
- 31P
- Phosphorus-31
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