The developmental patterns of the amygdala in children and adolescences have been inconsistent in previous studies. This discrepancy may be partly due to methodological differences in segmentation by tracing the human amygdala. To investigate the impact of tracing methods on amygdala volume, we compared FreeSurfer and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, as the Gold Standard, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae while volBrain produced smaller amygdalae. This tracing bias was larger for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project (total 427 magnetic resonance imaging scans from 198 participants aged 6-17 years at baseline). Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Comparing these trajectories, the shapes of developmental trajectories were similar when using the volBrain derived volumes while FreeSurfer led to more nonlinear and flattened, but statistically non-significant, growth patterns. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves across the three methods. Our findings revealed steady growth of the human amygdala, mirroring the functional development across the school age. We argue that methodological improvements are warranted for current automatic tools to achieve more accurate tracing of the amygdala at school age.
bioRxiv Subject Collection: Neuroscience