Background Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status. Procedure We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8–15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables. Results We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group. Conclusions This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity.

Reading and writing are related but separable processes that are crucial skills to possess in modern society. The neurobiological basis of reading acquisition and development, which critically depends on phonological processing, and to a lesser degree, beginning writing as it relates to letter perception, are increasingly being understood. Yet direct relationships between writing and reading development, in particular, with phonological processing is not well understood. The main goal of the current preliminary study was to examine individual differences in neurofunctional and neuroanatomical patterns associated with handwriting in beginning writers/readers. In 46 5-6 year-old beginning readers/writers, ratings of handwriting quality, were rank-ordered from best to worst and correlated with brain activation patterns during a phonological task using functional MRI, and with regional gray matter volume from structural T1 MRI. Results showed that better handwriting was associated negatively with activation and positively with gray matter volume in an overlapping region of the pars triangularis of right inferior frontal gyrus. This region, in particular in the left hemisphere in adults and more bilaterally in young children, is known to be important for decoding, phonological processing, and subvocal rehearsal. We interpret the dissociation in the directionality of the association in functional activation and morphometric properties in the right inferior frontal gyrus in terms of neural efficiency, and suggest future studies that interrogate the relationship between the neural mechanisms underlying reading and writing development.

No abstract

No abstract