Mapping corpus callosum surface reduction in fetal alcohol spectrum disorders with sulci and connectivity-based parcellation

Fetal alcohol spectrum disorders (FASD) range from fetal alcohol syndrome (FAS) to non-syndromic non-specific forms (NS-FASD) that are still underdiagnosed and could benefit from new neuroanatomical markers. The main neuroanatomical manifestation of prenatal alcohol exposure on developmental toxicity is the reduction in brain size, but repeated imaging observations have long driven the attention on the corpus callosum (CC), without being all convergent. Our study proposed a new segmentation of the CC that relies on both a sulci-based cortical segmentation and the "hemispherotopic" organization of the transcallosal fibers. We collected a monocentric series of 37 subjects with FAS, 28 with NS-FASD, and 38 with typical development (6 to 25 years old) using brain MRI (1.5T). Associating T1- and diffusion-weighted imaging, we projected a sulci-based cortical segmentation of the hemispheres on the midsagittal section of the CC, resulting in seven homologous anterior-posterior parcels (frontopolar, anterior and posterior prefrontal, precentral, postcentral, parietal, and occipital). We measured the effect of FASD on the area of callosal and cortical parcels by considering age, sex, and brain size as linear covariates. The surface proportion of the corresponding cortical parcel was introduced as an additional covariate. We performed a normative analysis to identify subjects with an abnormally small parcel. All callosal and cortical parcels were smaller in the FASD group compared with controls. When accounting for age, sex, and brain size, only the postcentral (η = 6.5%, p = 0.032) callosal parcel and % of the cortical parcel (η = 8.9%, p = 0.007) were still smaller. Adding the surface proportion (%) of the corresponding cortical parcel to the model, only the occipital parcel was persistently reduced in the FASD group (η = 5.7%, p = 0.014). In the normative analysis, we found an excess of subjects with FASD with abnormally small precentral and postcentral (peri-isthmic) and posterior-splenial parcels (p < 0.05). The objective sulcal and connectivity-based method of CC parcellation proved to be useful not only in confirming posterior-splenial damage in FASD but also in the narrowing of the peri-isthmic region strongly associated with a specific size reduction in the corresponding postcentral cortical region (postcentral gyrus). The normative analysis showed that this type of callosal segmentation could provide a clinically relevant neuroanatomical endophenotype, eve