Medial temporal lobe (MTL) is one of the key areas of memory function, demonstrating the most plastic component of the human brain. It expands from the subcortex to the cortex, including the complex nerve structure from the allocortex to the neocortex. Not only the spatial structures are distinguished from each other among the adjacent subdivisions of MTL, but also their cell constructions and positions on the signaling pathway are different. Because of its close relationship with aging and neurodegenerative diseases, many studies focus on MTL to reveal its specific morphological changes in aging or disease. However, developmental changes of its subdivisions across the human lifespan are still unknown.
Along with the continuous improvement of magnetic resonance imaging technology, it is now possible to explore how the MTL changes across lifespan. First, based on a multi-center cross-sectional data from the Nathan Kline Institute – Rockland Sample (N = 200, 6-80 years), Chinese Color Nest Project (N = 51, 7-17 years), Chinese Adult Lifespan Dataset (N = 149, 18-80 years), this study constructed a large sample of high-resolution structural MRI of human brain morphology across lifespan (N = 400, 6-80 years). Second, the MTL were divided into seven sub-divisions including the hippocampus (HP), the entorhinal cortex (EC), the perirhinal cortex (PRC), the presubiculum (PreS), and three parahippocampal areas (PHA) (PHA1, PHA2, PHA3), according to the parcellations from FreeSurfer and the Human Connectome Project. The multiple morphological metrics of the sub-divisions were derived: volume, surface area, cortical thickness and fractal dimensionality. By fitting linear regression model of each metric to age-related changes with controlling the covariates such as intracranial volume, sex and imaging parameters, significant lifespan changes were detected after Bonferroni correction. Estimation of the lifespan trajectory percentiles and prediction of these lifespan trajectories were achieved for each metric. Finally, in order to further investigate the longitudinal development model of MTL and its sub-divisions, we collected 429 longitudinal data from 198 Chinese typically developing school-age children and depicted their growth curves of each metrics during 6-20 years old, using the Generalized Addictive Mixed Models (GAMMs).
Our analyses demonstrated that: 1) the lifespan development of the MTL follows its basic spatial and functional distribution; 2) Subcortical area showed an inverted U-shaped across lifespan, keeping stable or increasing slowing during school age and decreasing progressively after 50 years old; 3) The lifespan changes of the cortical region are dominated by linear decreases, but there are local variations in the different sub-divisions. These lifespan development models are reproducible across different samples and centers. The obvious difference in PHA was from the cortical thickness. The present findings are using a high-precision parcellation, not only for the first time in the Chinese population to depict the MTL lifespan trajectory and growth curves, but also the first international systematic lifespan trajectory map of the MTL lifespan development. It will promote updating the knowledge of the MTL in the field of cognitive developmental neuroscience, as well as providing quantitative reference to the clinical monitoring, prevention, diagnosis of the MTL related brain diseases during the whole process form growth to aging.