Enhancing fetal alcohol spectrum disorders diagnosis with a classifier based on the intracerebellar gradient of volumetric undersizing.

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 = bVt a ), 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 (v DTS) learned in the controls. Lastly, we trained and tested two classifiers to discriminate FAS from controls, one based on the total cerebellum v DTS only, the other based on all the cerebellar v DTS, 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 (v DTS = -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 v DTS performed more efficiently than the one based on total cerebellum v DTS 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.

Maturity of white matter tracts is associated with episodic memory recall during development.

The structure-function relationship between white matter microstructure and episodic memory (EM) has been poorly studied in the developing brain, particularly in early childhood. Previous studies in adolescents and adults have shown that episodic memory recall is associated with prefrontal-limbic white matter microstructure. It is unknown whether this association is also observed during early ontogeny. Here, we investigated the association between prefrontal-limbic tract microstructure and EM performance in a cross-sectional sample of children aged 4 to 12 years. We used a multivariate partial least squares correlation approach to extract tract-specific latent variables representing shared information between age and diffusion parameters describing tract microstructure. Individual projections onto these latent variables describe patterns of interindividual differences in tract maturation that can be interpreted as scores of white matter tract microstructural maturity. Using these estimates of microstructural maturity, we showed that maturity scores of the uncinate fasciculus and dorsal cingulum bundle correlated with distinct measures of EM recall. Furthermore, the association between tract maturity scores and EM recall was comparable between younger and older children. Our results provide new evidence on the relation between white matter maturity and EM performance during development.

Three-Dimensional Probabilistic Maps of Mesial Temporal Lobe Structures in Children and Adolescents' Brains.

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/.

Near-infrared light is neuroprotective in a monkey model of Parkinson disease.

OBJECTIVE: To examine whether near-infrared light (NIr) treatment reduces clinical signs and/or offers neuroprotection in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson disease. METHODS: We implanted an optical fiber device that delivered NIr (670 nm) to the midbrain of macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.5-2.1mg/kg) were made over a 5- to 7-day period, during which time the NIr device was turned on. This was then followed by a 3-week survival period. Monkeys were evaluated clinically (eg, posture, bradykinesia) and behaviorally (open field test), and their brains were processed for immunohistochemistry and stereology. RESULTS: All monkeys in the MPTP group developed severe clinical and behavioral impairment (mean clinical scores = 21-34; n = 11). By contrast, the MPTP-NIr group developed much less clinical and behavioral impairment (n = 9); some monkeys developed moderate clinical signs (mean scores = 11-15; n = 3), whereas the majority--quite remarkably--developed few clinical signs (mean scores = 1-6; n = 6). The monkeys that developed moderate clinical signs had hematic fluid in their optical fibers at postmortem, presumably limiting NIr exposure and overall clinical improvement. NIr was not toxic to brain tissue and offered neuroprotection to dopaminergic cells and their terminations against MPTP insult, particularly in animals that developed few clinical signs. INTERPRETATION: Our findings indicate NIr to be an effective therapeutic agent in a primate model of the disease and create the template for translation into clinical trials.