Myelination of a Key Relay Zone in the Hippocampal Formation Occurs in the Human Brain During Childhood, Adolescence, and Adulthood

TLDR

Previous studies have shown that myelination of the superior medullary lamina on the parahippocampal gyrus occurs during adolescence, though the exact axonal origins remain unclear, possibly involving perforant path and cingulum fibers. The study aimed to determine whether myelination of this region continues into the second decade and beyond by analyzing 164 normal individuals from newborn to 76 years. The authors examined blinded cross‑sections of the hippocampal formation and adjacent gyrus, scoring myelin with a global rating scale or by measuring stained area. Myelination of the superior medullary lamina increased curvilinearly from infancy to the sixth decade, with a twofold rise in the first two decades and a further 60% rise in later decades, greater in females up to age 29, and expanding from the subiculum to lateral presubiculum over time, confirming early and late postnatal myelination in this corticolimbic relay.

Abstract

<h3>Background:</h3> A previous study demonstrated that myelination of the superior medullary lamina along the surface of the parahippocampal gyrus is occurring in human brain during adolescence. To further investigate whether postnatal increases of myelination may continue during the second decade and possibly even longer, the extent of myelination in this region has been analyzed in 164 psychiatrically normal individuals aged newborn to 76 years. <h3>Methods:</h3> Cross sections of the hippocampal formation with adjoining hippocampal gyrus were analyzed on a blinded basis using either a global rating scale or measurements of the area of myelin staining. <h3>Results:</h3> A curvilinear increase in the extent of myelination between the first and sixth decades of life (<i>r</i>=.71 and<i>r</i>=.67, respectively) was observed. When the area of myelination was expressed relative to brain weight, there was a twofold increase between the first and second decades and an additional increase of 60% between the fourth and sixth decades. Female subjects showed a significantly greater degree of myelin staining than did male subjects during the interval of ages 6 to 29 years; however, after the third decade, there were no gender differences in the area of myelin staining. <h3>Conclusions:</h3> The increased staining of myelin during the first and second decades principally occurred in the subicular region and adjacent portions of the presubiculum. During the fourth through sixth decades, however, it extended to progressively more lateral locations along the surface of the presubiculum. The precise origin(s) of the axons showing progressive myelination is unknown; however, the axons in the subiculum may include some perforant path fibers, while those found in the presubiculum may include cingulum bundle projections. Overall, our data are consistent with the idea that both early and late postnatal increases of myelination occur in a key corticolimbic relay area of the human brain and underscore the importance of applying a neurodevelopmental perspective to the study of psychopathology during childhood, adolescence, and even adulthood.