In fetal alcohol spectrum disorders (FASD), brain growth deficiency is a hallmark of subjects both with fetal alcohol syndrome (FAS) and with non‐syndromic FASD (NS‐FASD, i.e., those without specific diagnostic features). However, although the cerebellum was suggested to be more severely undersized than the rest of the brain, it has not yet been given a specific place in the FASD diagnostic criteria where neuroanatomical features still count for little if anything in diagnostic specificity. We applied a combination of cerebellar segmentation tools on a 1.5 T 3DT1 brain MRI dataset from a monocentric population of 89 FASD (52 FAS, 37 NS‐FASD) and 126 typically developing controls (6–20 years old), providing 8 volumes: cerebellum, vermis and 3 lobes (anterior, posterior, inferior), plus total brain volume. After adjustment of confounders, the allometric scaling relationship between these cerebellar volumes (Vi) and the total brain or cerebellum volume (Vt) was fitted (Vi = bVta), and the effect of group (FAS, control) on allometric scaling was evaluated. We then estimated for each cerebellar volume in the FAS population the deviation from the typical scaling (vDTS) learned in the controls. Lastly, we trained and tested two classifiers to discriminate FAS from controls, one based on the total cerebellum vDTS only, the other based on all the cerebellar vDTS, comparing their performance both in the FAS and the NS‐FASD group. Allometric scaling was significantly different between FAS and control group for all the cerebellar volumes (p < .001). We confirmed the excess of total cerebellum volume deficit (vDTS = −10.6%) and revealed an antero‐inferior‐posterior gradient of volumetric undersizing in the hemispheres (−12.4%, 1.1%, 2.0%, respectively) and the vermis (−16.7%, −9.2%, −8.6%, repectively). The classifier based on the intracerebellar gradient of vDTS performed more efficiently than the one based on total cerebellum vDTS only (AUC = 92% vs. 82%, p = .001). Setting a high probability threshold for >95% specificity of the classifiers, the gradient‐based classifier identified 35% of the NS‐FASD to have a FAS cerebellar phenotype, compared to 11% with the cerebellum‐only classifier (pFISHER = 0.027). In a large series of FASD, this study details the volumetric undersizing within the cerebellum at the lobar and vermian level using allometric scaling, revealing an anterior‐inferior‐posterior gradient of vulnerability to prenatal alcohol exposure. It also strongly suggests that this intracerebellar gradient of volumetric undersizing may be a reliable neuroanatomical signature of FAS that could be used to improve the specificity of the diagnosis of NS‐FASD.
The hippocampus and the adjacent perirhinal, entorhinal, temporopolar, and parahippocampal cortices are interconnected in a hierarchical MTL system crucial for memory processes. A probabilistic description of the anatomical location and spatial variability of MTL cortices in the child and adolescent brain would help to assess structure-function relationships. The rhinal sulcus (RS) and the collateral sulcus (CS) that border MTL cortices and influence their morphology have never been described in these populations. In this study, we identified the aforementioned structures on magnetic resonance images of 38 healthy subjects aged 7–17 years old. Relative to sulcal morphometry in the MTL, we showed RS-CS conformation is an additional factor of variability in the MTL that is not explained by other variables such as age, sex and brain volume; with an innovative method using permutation testing of the extrema of structures of interest, we showed that RS-SC conformation was not associated with differences of location of MTL sulci. Relative to probabilistic maps, we offered for the first time a systematic mapping of MTL structures in children and adolescent, mapping all the structures of the MTL system while taking sulcal morphology into account. Our results, with the probabilistic maps described here being freely available for download, will help to understand the anatomy of this region and help functional and clinical studies to accurately test structure-function hypotheses in the MTL during development.Free access to MTL pediatric atlas: http://neurovault.org/collections/2381/.
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