Abstract
Structural neuroimaging studies of typical development reveal increases in grey matter volume during childhood, followed by shrinkage in adolescence and early adulthood. With neuropil constituting the bulk of grey 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 to 14 years at baseline (37 boys, 12 girls) were assessed on up to three occasions approximately 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.
Significance Statement In childhood and adolescence, structural neuroimaging reveals marked changes in the brain’s grey matter, most likely indicating contraction and expansion of its main component – the neuropil. The neurobiological mechanisms of these changes are, however, poorly understood. In the first of its kind longitudinal study of 6- to 14-year-old children, we examined in vivo changes in metabolites associated with brain energetics and the synthesis and degradation of membrane phospholipids using phosphorus magnetic resonance spectroscopy. We identify developmental changes in the metabolites associated with contraction and expansion of the neuropil and their coupling with structural changes in late-to-mature brain regions of the prefrontal cortex, indicating candidate mechanisms of brain development.
Footnotes
The authors declare no conflicts of interest.
This research was supported in part by grants NIH R01 MH65420 (JAS), NIH R01 AG011230 (NR), and the Lycaki-Young Funds from the State of Michigan (JAS). The authors thank Theodoros Koustakas for support with data preprocessing.
