The hippocampus is an anatomically and functionally heterogeneous structure, but longitudinal studies of its regional development are scarce and it is not known whether protracted maturation of the hippocampus in adolescence is related to memory development. First, we investigated hippocampal subfield development using 170 longitudinally acquired brain magnetic resonance imaging scans from 85 participants aged 8-21 years. Hippocampal subfield volumes were estimated by the use of automated segmentation of 7 subfields, including the cornu ammonis (CA) sectors and the dentate gyrus (DG), while longitudinal subfield volumetric change was quantified using a nonlinear registration procedure. Second, associations between subfield volumes and change and verbal learning/memory across multiple retention intervals (5 min, 30 min and 1 week) were tested. It was hypothesized that short and intermediate memory would be more closely related to CA2-3/CA4-DG and extended, remote memory to CA1. Change rates were significantly different across hippocampal subfields, but nearly all subfields showed significant volume decreases over time throughout adolescence. Several subfield volumes were larger in the right hemisphere and in males, while for change rates there were no hemisphere or sex differences. Partly in support of the hypotheses, greater volume of CA1 and CA2-3 was related to recall and retention after an extended delay, while longitudinal reduction of CA2-3 and CA4-DG was related to learning. This suggests continued regional development of the hippocampus across adolescence and that volume and volume change in specific subfields differentially predict verbal learning and memory over different retention intervals, but future high-resolution studies are called for.

Many brain structures show a complex, non-linear pattern of maturation and age-related change. Often, quadratic models (beta(0) + beta(1)age + beta(2)age(2) + epsilon) are used to describe such relationships. Here, we demonstrate that the fitting of quadratic models is substantially affected by seemingly irrelevant factors, such as the age-range sampled. Hippocampal volume was measured in 434 healthy participants between 8 and 85 years of age, and quadratic models were fit to subsets of the sample with different age-ranges. It was found that as the bottom of the age-range increased, the age at which volumes appeared to peak was moved upwards and the estimated decline in the last part of the age-span became larger. Thus, whether children were included or not affected the estimated decline between 60 and 85 years. We conclude that caution should be exerted in inferring age-trajectories from global fit models, e.g. the quadratic model. A nonparametric local smoothing technique (the smoothing spline) was found to be more robust to the effects of different starting ages. The results were replicated in an independent sample of 309 participants.