Developmental Changes in Brain Cellular Membrane and Energy Metabolism: A Multi-occasion ³¹P Magnetic Resonance Spectroscopy Study

Structural neuroimaging studies of typical development reveal increases in gray matter volume during childhood, followed by shrinkage in adolescence and early adulthood. With neuropil constituting the bulk of gray matter, these developmental changes may reflect neuropil reorganization accompanied by alterations in cellular membranes, as well as changes in related energy demand. Phosphorus magnetic resonance spectroscopy (³¹P MRS) allows in vivo assessment of changes in the brain’s high-energy phosphates—phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine triphosphate (ATP)—as well as metabolites associated with synthesis and degradation of membrane phospholipids (MPLs)—phosphocholine (PC) and phosphoethanolamine (PE)—and their breakdown products, glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE). Forty-nine children and adolescents aged 6–14 years at baseline (37 boys, 12 girls) were assessed on up to three occasions ca. 12 months apart. MPL precursor levels decreased across all examined regions over time, including cortical and subcortical gray matter and two major white matter tracts. Breakdown products increased in the prefrontal cortex (PFC) in younger children but decreased in their older counterparts. While ATP and Pi decreased across most regions, PCr changes were heterochronic and regional: hippocampal increases were more pronounced in older children, whereas most of the remaining regions showed no change. Changes in MPL precursors were positively associated with change in PFC cortical thickness, suggesting that the expansion and contraction of neuropil are coupled with structural brain changes during childhood and adolescence. Thus, in vivo ³¹P MRS provides new insights into the neurobiological mechanisms of normal brain development.