Cortical Development

Cochlear implantation (CI) for profound congenital hearing impairment, while often successful in restoring hearing to the deaf child, does not always result in effective speech processing. Exposure to non-auditory signals during the pre5
implantation period is widely held to be responsible for such failures.
Here, we question the inference that such exposure irreparably distorts the function of auditory cortex, negatively impacting the efficacy of cochlear implantation. Animal studies suggest that in congenital early deafness there is a disconnection
between (disordered) activation in primary auditory cortex (A1) and activation in secondary auditory cortex (A2). In humans, One factor contributing to this functional decoupling is assumed to be abnormal activation of A1 by visual projections – including exposure to sign language. In this paper we show that that this abnormal activation of A1 does not routinely occur, while A2 functions effectively supramodally and multimodally to deliver spoken language irrespective of hearing status.
What, then, is responsible for poor outcomes for some individuals with CI and for apparent abnormalities in cortical organization in these people? Since infancy is a critical period for the acquisition of language, deaf children born to hearing parents are at risk of developing inefficient neural structures to support skilled language processing. A sign language, acquired by a deaf child as a first language in a signing environment, is cortically organized like a heard spoken language in terms of specialization of the dominant perisylvian system. However, very few deaf children are exposed to sign language in early infancy. Moreover, no studies to date have examined sign language proficiency in relation to cortical organization in individuals with CI.
Given the paucity of such relevant findings, we suggest that the best guarantee of good language outcome after CI is the establishment of a secure first language pre implant – however that may be achieved, and whatever the success of auditory
restoration.

Only about five percent of our genome contains human-specific sequences. These sequences arose mostly from segmental duplications during human evolution and include genes that are unique to the human lineage. Although these genes are currently not well characterised, they may be potential key players in the development of human-specific traits, like an expanded neocortex. Here, we present an overview of the role of human-specific genes during development and evolution of the embryo - nic brain, with a focus on one of these genes, ARHGAP11B (Rho GTPase Activating Protein 11B).

Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. Here, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of the Rho GTPase-activating-protein–encoding ARHGAP11A on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal, and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

Schizencephaly is an uncommon structural disorder of cerebral cortical development, characterized by congenital clefts spanning the cerebral hemispheres from the pial surface to the lateral ventricles and lined by cortical gray matter. Either an antenatal environmental incident or a genetic origin could be responsible for this lesion which occurs between the third and fourth month of gestation. We report the clinical and cranial imaging features of 30 children, of whom 15 had unilateral and 15 had bilateral lesions. Their ages at the time of the first presentation ranged from 1 month to 10 years. They were thoroughly studied from clinical, epileptical, imaging and electroencephalographic (EEG) viewpoints. Five patients were investigated by cranial computed tomography (CT), eight by cranial magnetic resonance (MR) imaging, and 17 by both methods. The clinical features consisted of mild hemiparesis in 17 cases (57%), 12/17 were related to a unilateral phenotype (80% of all unilateral forms) and 5/17 to a bilateral phenotype. A tetraparesis was present in nine cases, all of which were due to a bilateral cleft. Bilateral forms were significantly associated with tetraparesis, whereas unilateral forms were associated with hemiparesis. Mental retardation was observed in 17 cases (57%), and was observed significantly more often in bilateral clefts (80%). When both hemispheres are involved, an absence of reorganization of the brain function between the two hemispheres leads to severe mental deficits, in addition to the cerebral anomaly itself. Eleven patients had seizures (seven from unilateral and three from bilateral forms). The degree of malformation was not related to the severity of epilepsy. Migration disorders, such as dysplasia or heterotopia, were observed in 30% of cases and are also important etiopathogenetic factors. The septum pellucidum was absent in 13 cases (43%), with septo-optical dysplasia in two cases. Corpus callosum dysgenesis was noted in 30% of cases. Four cases of mega cisterna magna were noted. Although familial cases and environmental factors have been previously reported, schizencephaly appears to be, in the majority of cases, sporadic.