Neural correlates of working memory in children and adolescents with agenesis of the corpus callosum: An fMRI study.

The ability to temporarily maintain relevant information in mind in the presence of interference or distracting information, also called working memory (WM), is critical for higher cognitive functions and cognitive development. In typically developing (TD) children, WM is underpinned by a fronto-parietal network of interacting left and right brain regions. Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation. This study aims to investigate functional organisation of WM in children and adolescents with AgCC using functional magnetic resonance imaging (fMRI). Nine children with AgCC and a comparison group of sixteen TD children aged 8-17 years completed an fMRI WM paradigm designed to enable investigation of different WM processes, i.e., encoding, maintenance and retrieval. We found that AgCC children recruited globally similar brain regions as the TD comparison group during the WM task, despite significant disparity in brain development, i.e., bilateral occipito-frontal activations during verbal encoding, and bilateral fronto-parietal executive control network during retrieval. However, compared to their TD peers, children with AgCC seemed less able to engage lateralised brain systems specialised for particular memory material (i.e. less supramarginal activations for verbal material and less fusiform activations for face processing) and particular memory process (i.e. absence of right-predominant activations during retrieval). Group differences in the pattern of activation might also reflect different cognitive strategies to cope with competition in processing resources with different susceptibility to concurrent tasks (verbal vs visual), such as differential recruitment of associative visual areas and executive prefrontal regions in the AgCC compared with the TD group depending on the concurrent task completed during maintenance. This study provides a first step towards a better understanding of functional brain networks underlying higher cognitive functions in children with AgCC.

The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity.

Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.