A Neuropsychological Profile for Agenesis of the Corpus Callosum?: Cognitive, Academic, Executive, Social, and Behavioral Functioning in School-Age Children

Objectives: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Methods: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. Results: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. Conclusions: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention

Large-scale functional network dynamics in human callosal agenesis:Increased subcortical involvement and preserved laterality

In the human brain, the corpus callosum is the major white-matter commissural tract enabling the transmission of sensory-motor, and higher level cognitive information between homotopic regions of the two cerebral hemispheres. Despite developmental absence (i.e., agenesis) of the corpus callosum (AgCC), functional connectivity is preserved, including interhemispheric connectivity. Subcortical structures have been hypothesised to provide alternative pathways to enable this preservation. To test this hypothesis, we used functional Magnetic Resonance Imaging (fMRI) recordings in children with AgCC and typically developing children, and a time-resolved approach to retrieve temporal characteristics of whole-brain functional networks. We observed an increased engagement of the cerebellum and amygdala/hippocampus networks in children with AgCC compared to typically developing children. There was little evidence that laterality of activation networks was affected in AgCC. Our findings support the hypothesis that subcortical structures play an essential role in the functional reconfiguration of the brain in the absence of a corpus callosum

Revisiting brain rewiring and plasticity in children born without corpus callosum

The corpus callosum is the largest white matter pathway connecting homologous structures of the two cerebral hemispheres. Remarkably, children and adults with developmental absence of the corpus callosum (callosal dysgenesis, CD) show typical interhemispheric integration, which is classically impaired in adult split-brain patients, for whom the corpus callosum is surgically severed. Tovar-Moll and colleagues (2014) proposed alternative neural pathways involved in the preservation of interhemispheric transfer. In a sample of six adults with CD, they revealed two homotopic bundles crossing the midline via the anterior and posterior commissures and connecting parietal cortices, and the microstructural properties of these aberrant bundles were associated with functional connectivity of these regions. The aberrant bundles were specific to CD and not visualised in healthy brains. We extended this study in a developmental cohort of 20 children with CD and 29 typically developing controls (TDC). The two anomalous white-matter bundles were visualised using tractography. Associations between structural properties of these bundles and their regional functional connectivity were explored. The proposed atypical bundles were observed in 30% of our CD cohort crossing via the anterior commissure, and in 30% crossing via the posterior commissure (also observed in 6.9% of TDC). However, the structural property measures of these bundles were not associated with parietal functional connectivity, bringing into question their role and implication for interhemispheric functional connectivity in CD. It is possible that very early disruption of embryological callosal development enhances neuroplasticity and facilitates the formation of these proposed alternative neural pathways, but further evidence is needed

Anterior and posterior commissures in agenesis of the corpus callosum: alternative pathways for attention processes?

Developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation resulting from disruption of corpus callosum formation, a structure that is crucial for the transfer and integration of information, including attention processes, across the brain. This study aimed to investigate previously proposed candidates for alternative inter-hemispheric pathways in AgCC by examining (1) white matter volume and microstructure of the anterior and posterior commissures in children with AgCC compared to typically developing controls (TDC), and (2) in children with AgCC, examine the associations of white matter volume and microstructure of the anterior and posterior commissures and any remaining corpus callosum with attention processes. Participants were 21 children with AgCC (13 complete, 8 partial) recruited from The Royal Children's Hospital, Melbourne, and 30 TDC aged 8–17 years. T1-and diffusion-weighted MR sequences were used to calculate volume and microstructural parameters. Neuropsychological testing assessed attention processes. We found the anterior commissure was significantly larger in volume in children with AgCC than TDC (p = .027), with reduced mean FA (p = .001) associated with increased mean RD (p < .001). In children with AgCC, we found microstructural properties of the anterior commissure associated with attentional processes, specifically, mean FA of the anterior commissure was associated with better divided attention (p = .03), and the association between alerting attention and mean AD and RD was found to be moderated by age (p = .027, p = .008) and the degree of corpus callosum agenesis (p = .025, p = .016). Furthermore, in partial AgCC, larger posterior commissure volume was associated with better orienting attention (p = .035). In conclusion, we provide evidence that the volume and microstructure of the anterior commissure are altered in children with AgCC, and this neuroplastic response might have an influence on attention processes

Neuropsychology and functional brain organisation of working memory in children and adolescents with agenesis of the corpus callosum

© 2017 Dr. Vanessa SiffrediCompleted under a Cotutelle arrangement between the University of Melbourne and Université de GenéveBackground: The corpus callosum is the largest brain white matter pathway. Its main function is to coordinate and transfer information between the two hemispheres, thus contributing to higher cognitive functions including working memory (WM). Developmental absence of the corpus callosum, or Agenesis of the Corpus Callosum (AgCC), is one of the most common brain malformations but its consequences on neurobehavioural functioning and functional brain organisation in school-age children are not well understood. Aims: The goal of the current work was: 1) To describe the impact of AgCC on neurobehavioural functioning, including WM functions, in school-age children; and investigate the role of age, social, and neurological factors that might underlie neurobehavioural outcomes in children with AgCC; 2) To investigate the functional brain organisation of WM in school-age children with AgCC using functional magnetic resonance imaging (fMRI). Methods: 28 children diagnosed with AgCC based on MRI and a control sample of 16 typically developing children, aged 8 to 17 years, completed a neurobehavioural assessment and brain imaging with anatomical T1 sequences and an fMRI task (AgCC, n=9; controls, n=16) tapping WM processes, i.e., encoding, maintenance and retrieval. Parents and teachers completed questionnaires to evaluate executive, behavioural and social functions. Results: In our cohort, ~50% experienced general intellectual, academic, executive, social and/or behavioural difficulties and ~20% reached a level comparable to typically developing children. Social risk was found to have an important impact on variability in functional outcomes. Additional brain anomalies or complete AgCC were associated with lower mathematics performance and poorer executive functioning. fMRI findings showed that globally similar brain regions were recruited in the AgCC and the control groups 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, there were notable differences in activations between groups that might reflect different susceptibility to concurrent tasks during WM, subsequent to different degrees of hemispheric lateralisation during the task. Conclusion: This work constitutes the first comprehensive report of cognitive, executive, behavioural and social consequences of AgCC in school-age children, and provides a first step towards a better understanding of functional brain networks underlying higher cognitive functions in children with AgCC

La dyslexie développementale : discussion autour des profils de dyslexie chez l'enfant

Le modèle de lecture à deux voies en cascade (Coltheart, Rastle, Perry, Langdon & Ziegler, 2001), fondé sur des travaux réalisés chez l'adulte cérébro-lésé, propose deux voies de lecture : la voie sous-lexicale et la voie lexicale. Dans ces travaux, l'altération de l'une ou l'autre de ces deux voies de lecture entraîne deux profils distincts d'alexie : phonologique et de surface. L'existence de différents profils de dyslexie développementale chez l'enfant, aussi appelé trouble spécifique de l'acquisition de l'identification des mots écrits (Zesiger, 2004), est aujourd'hui discutée par de nombreux auteurs (Sprenger-Charolles & Colé, 2003). En nous appuyant sur l'étude de quatre cas d'enfants présentant une dyslexie développementale, d'âges différents, et se trouvant à différents stades d'acquisition de la lecture, nous discutons ici l'existence de ces deux profils chez l'enfant dyslexique. Les performances dans des épreuves de lecture de mots irréguliers et de logatomes, vont dans le sens d'une distribution continue des enfants dyslexiques selon le degré de sévérité de leurs déficits dans l'une et/ou l'autre des deux voies de lecture (Murphy & Pollatsek, 1994). La majorité des enfants de notre échantillon se trouvent donc au milieu de ce continuum, en fonction de l'atteinte sur les voies sous-lexicales et lexicales, plutôt qu'aux extrémités avec un profil de dyslexie bien distinct, phonologique ou de surface

Neuropsychological profile of agenesis of the corpus callosum: a systematic review

Developmental absence (agenesis) of the corpus callosum (AgCC) is a common brain malformation that presents in isolation or in association with other conditions. Variability in aspects of neuropsychological functioning has been reported in small samples of individuals. This study aimed to systematically review the literature to characterize the profile and severity of cognitive impairments in individuals with AgCC across development. A mean general intellectual ability was calculated and neuropsychological functioning was qualitatively examined. We discuss methodological limitations of the literature, inherent heterogeneity of the causes and comorbidities of AgCC, and the developmental aspect of AgCC in opposition to split-brain patients

Examining distinct working memory processes in children and adolescents using fMRI: Results and validation of a modified Brown-Peterson paradigm

Verbal working memory (WM) comprises different processes (encoding, maintenance, retrieval) that are often compromised in brain diseases, but their neural correlates have not yet been examined in childhood and adolescence. To probe WM processes and associated neural correlates in developmental samples, and obtain comparable effects across different ages and populations, we designed an adapted Brown-Peterson task (verbal encoding and retrieval combined with verbal and visual concurrent tasks during maintenance) to implement during functional magnetic resonance imaging (fMRI). In a sample of typically developing children and adolescents (n = 16), aged 8 to 16 years, our paradigm successfully identified distinct patterns of activation for encoding, maintenance, and retrieval. While encoding activated perceptual systems in posterior and ventral visual regions, retrieval activated fronto-parietal regions associated with executive control and attention. We found a different impact of verbal versus visual concurrent processing during WM maintenance: at retrieval, the former condition evoked greater activations in visual cortex, as opposed to selective involvement of language-related areas in left temporal cortex in the latter condition. These results are in accord with WM models, suggesting greater competition for processing resources when retrieval follows within-domain compared with cross-domain interference. This pattern was found regardless of age. Our study provides a novel paradigm to investigate distinct WM brain systems with reliable results across a wide age range in developmental populations, and suitable for participants with different WM capacities