Whole-brain phosphorus metabolism: regional distribution and associations with cognition
Poster No:
1960
Submission Type:
Abstract Submission
Authors:
Mariia Ptukha1, Bradford Moffat2, Andrew Zalesky3,4, Vanessa Cropley5
Institutions:
1Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia, 2Melbourne Brain Centre Imaging Unit, Department of Radiology, University of Melbourne, Melbourne, Australia, 3Department of Psychiatry, Melbourne Medical School,The University of Melbourne, Melbourne, Australia, 4Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne, Melbourne, Australia, 5Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
First Author:
Co-Author(s):
Bradford Moffat
Melbourne Brain Centre Imaging Unit, Department of Radiology, University of Melbourne
Melbourne, Australia
Melbourne Brain Centre Imaging Unit, Department of Radiology, University of Melbourne
Melbourne, Australia
Andrew Zalesky
Department of Psychiatry, Melbourne Medical School,The University of Melbourne|Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne
Melbourne, Australia|Melbourne, Australia
Department of Psychiatry, Melbourne Medical School,The University of Melbourne|Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne
Melbourne, Australia|Melbourne, Australia
Introduction:
Studying brain metabolism can provide unique insight into the processes that underlie changes in brain structure and function, which occur in normal and pathological states. Phosphorus (31P) magnetic resonance spectroscopy (MRS) allows for visualization of metabolic content for crucial high-energy phosphates and membrane phospholipids. These compounds provide the basis for the normal functioning of the brain on a cellular level, while changes in their content are associated with pathological states (Harper et al., 2017; Jett et al., 2023) and have been shown to correlate with cognitive measures (Jett et al., 2022; Mosconi et al., 2021; Rae et al., 2003). However, only a select number of studies have been able to assess the distribution of high-energy and membrane phosphates across the whole brain in healthy people (Jett et al., 2022; Rietzler et al., 2022; Schmitz et al., 2018). In this study, we utilize 31P-MRS to examine regional heterogeneity in phosphorus-containing metabolites and assess how energy and membrane metabolism may impact cognition in healthy young adults.
Methods:
Whole-brain 31P-MRS spectra (10x10x8 voxels) were collected from 74 healthy volunteers (32 male, 42 female) aged 18 to 40 years (mean age 26.2 years). 3D maps of phosphocreatine (PCr), adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (tNAD), phosphomonoesters (PME) and phosphodiesters (PDE) were quantified using an established convolutional neural network a (Songeon et al., 2022) (31P-SPAWNN)). ATP, tNAD, PCr, PME and PDE were referenced to total phosphorus and assessed for voxel-wise whole brain distribution, as well as ratios ATP/PCr and PME/PDE. Concentrations were also calculated for 7 brain regions: frontal, occipital, parietal and temporal lobes, basal ganglia, thalamus and cerebellum. MATRICS Consensus Cognitive Battery was administered to obtain a global cognitive score and 5 cognitive domain scores: executive function, processing speed, working memory, verbal and visual learning. We tested for possible correlations of metabolic content with age, sex and cognitive measures at the voxel level using cluster-based permutation testing in PALM, FSL. We used Friedman's test with post hoc Wilcoxon's tests for within-subject differences between regions.
Results:
Whole-brain maps of energy metabolism (ATP, tNAD, PCr, ATP/PCr) and membrane metabolism (PME, PDE, PME/PDE) were estimated (Fig.1). Regional analysis demonstrated significant heterogeneity in metabolite distribution across brain regions for all assessed metabolites (p<0.0001). Voxel-wise analysis showed a significant negative correlation of tNAD with age (Fig.2A), as well as higher PME content in females (Fig.2B) (p value range <0.05). Negative correlations of phosphocreatine in parietal lobe voxels were found with global cognition and verbal learning (Fig.2C,D) (p value range <0.05). ATP/PCr and tNAD were found to correlate positively with verbal learning in parts of the parietal and frontal cortex (Fig.2E,F) (p value range <0.05).
·Figure 1. Maps of metabolite distribution across the brain.
·Figure 2. Associations of brain metabolism with age (A), sex (B) and cognition (C-F).
Conclusions:
Firstly, we have demonstrated that in young healthy adults, energy and membrane metabolism significantly vary across brain regions, which advances on findings from previous 31P MRS studies and data from FDG-PET (Berti et al., 2014; Subtirelu et al., 2023). Secondly, for the first time, we assess the link between cognitive measures and energy and membrane metabolism markers at voxel resolution. Our findings highlight the potential link between phosphate-containing energy metabolites and cognitive performance, particularly verbal learning, aligning with previous evidence (Jett et al., 2022; Mosconi et al., 2021; Rae et al., 2003). Overall, this study significantly advances our understanding of phosphate metabolite distribution across the brain in healthy individuals and its potential impact on cognitive function.
Higher Cognitive Functions:
Higher Cognitive Functions Other
Learning and Memory:
Learning and Memory Other
Novel Imaging Acquisition Methods:
MR Spectroscopy 1
Physiology, Metabolism and Neurotransmission:
Cerebral Metabolism and Hemodynamics 2
Keywords:
ADULTS
Cognition
Magnetic Resonance Spectroscopy (MRS)
MR SPECTROSCOPY
NORMAL HUMAN
Other - Cerebral metabolism; Whole-brain
1|2Indicates the priority used for review
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2. Harper, D. G. (2017). Tissue Type-Specific Bioenergetic Abnormalities in Adults with Major Depression. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 42(4), 876–885.
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5. Mosconi, L. (2021). Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Scientific Reports, 11(1), 10867.
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