Characterising the association between posterior parietal metabolite levels and cortical macrostructure in a cohort spanning childhood to adulthood.

Abstract

Postnatal brain development is characterised by dynamic macrostructural changes, including cortical thinning and cortical flattening during childhood and adolescence. These macro-structural changes are parallel with developmental changes in brain neurochemistry, probed in the human brain using Magnetic Resonance Spectroscopy (MRS). This includes neurotransmitters such glutamate and gamma-aminobutyric acid (GABA), as well as building blocks of neuronal and associated tissue such as N-acetyl aspartate (NAA), and those involved in metabolism such as creatine (Cr). While previous research has linked MRS-measured neuro-metabolite levels to bulk tissue composition (e.g., gray matter, white matter, and cerebrospinal fluid), the relationship between neurochemistry and more granular macrostructural metrics, such as cortical thickness, area, volume, and local gyrification, remains unexplored. This study investigates the association between MRS-measured neuro-metabolite levels in the posterior parietal cortex (PPC) and PPC-voxel cortical macrostructural metrics in a developmental cohort of 86 individuals aged 5-35 years. We also examine whether PPC metabolite concentrations associate with whole-brain structural metrics to determine whether associations are region-specific or more broadly generalisable. Our findings reveal significant positive associations between PPC cortical thickness, volume, local gyrification index (LGI) and Glx (glutamate + glutamine) levels, likely because differences in cortical microstructure, including dendritic arbour complexity, contributes to variation in both cortical macrostructure and Glx activity across development. Additionally, PPC Glx:GABA+ ratio negatively associated with subcortical gray matter volume, while PPC total NAA positively associated with cerebral white matter volume, suggesting a link between regional neurochemistry and broader brain structure. These results highlight the importance of accounting for macrostructural and broader brain structural characteristics when interpreting the neuroanatomical correlates of MRS-measured metabolites, beyond controlling for bulk tissue composition. This approach is particularly crucial when comparing neuro-metabolite levels across groups with known structural differences, such as developmental cohorts or individuals with neurodevelopmental conditions. Key pointsO_LIPosterior parietal cortex (PPC) Glx levels are positively associated with PPC cortical thickness and local gyrification index, likely because differences in cortical microstructure, including dendritic arbour complexity, contributes to both cortical macrostructure and neuro-metabolic traits across development. C_LIO_LIThe PPC Glx:GABA+ ratio is negatively associated with subcortical gray matter volume, while PPC total NAA is positively associated with cerebral white matter volume, suggesting a link between regional neurochemistry and broader brain structure. C_LIO_LIThese findings emphasise the importance of considering more detailed macrostructural characteristics, as well as bulk tissue composition (white matter, gray matter, cerebral spinal fluid), when interpreting MRS-measured metabolite differences. C_LI