Cutting, L. E. | bioRxiv Science

bioRxiv2024

Development of the Left Arcuate Fasciculus is Linked to Learning Gains in Reading, but not Math

Past studies leveraging cross-sectional data have raised questions surrounding the relationship between diffusion properties of the white matter and academic skills. Some studies have suggested that white matter properties serve as static predictors of academic skills, whereas other studies have observed no such relationship. On the other hand, longitudinal studies have suggested that within-individual changes in the white matter are linked to learning gains over time. In the present study, we look to replicate and extend the previous longitudinal results linking longitudinal changes in the white matter properties of the left arcuate fasciculus to individual differences in reading development. To do so, we analyzed diffusion MRI data, along with reading and mathematics scores in a longitudinal sample of 340 students as they progressed from 1st grade into 4th grade. Longitudinal growth models revealed that year-to-year within-individual changes in reading scores, but not math, were related to the development of the left arcuate fasciculus. These findings provide further evidence linking the dynamics of white matter development and learning in a unique sample and highlight the importance of longitudinal designs.

neuroscience↗

bioRxiv2022

Behavioral and imaging analysis of Foxg1 heterozygous mice

FOXG1 Syndrome (FS) is a devastating neurodevelopmental disorder that is caused by a heterozygous loss-of-function (LOF) mutation of the FOXG1 gene, which encodes a transcriptional regulator important for telencephalic brain development. People with FS have marked developmental delays, impaired ambulation, movement disorders, seizures, and behavior abnormalities including autistic features. Current therapeutic approaches are entirely symptomatic, however the ability to rescue phenotypes in mouse models of other genetic neurodevelopmental disorders such as Rett syndrome, Angelman syndrome, and Phelan-McDermid syndrome by postnatal expression of gene products has led to hope that similar approaches could help modify the disease course in other neurodevelopmental disorders such as FS. While FoxG1 protein function plays a critical role in embryonic brain development, the ongoing adult expression of FoxG1 and behavioral phenotypes that present when FoxG1 function is removed postnatally provides support for opportunity for improvement with postnatal treatment. Here we generated a new mouse allele of Foxg1 that disrupts protein expression and characterized the behavioral and structural brain phenotypes in heterozygous mutant animals. These mutant animals display changes in locomotor behavior, gait, anxiety, social interaction, aggression, and learning and memory compared to littermate controls. Additionally, they have structural brain abnormalities reminiscent of people with FS. This information provides the framework for future studies to evaluate the potential for post-natal expression of FoxG1 to modify the disease course in this severe neurodevelopmental disorder.

neuroscience↗