Functional connectivity reveals increased network segregation and sensorimotor processing during working memory in adolescents with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a rare genetic condition characterised by skin pigmentations, bone deformities, and tumours. Its cognitive phenotype shares similarities with autism spectrum disorder and attention deficit/hyperactivity disorder, including impairments in executive function and working memory processing. In this work, we conducted functional connectivity and graph theory analysis of fMRI data from a sample of neurotypical adolescents (N = 26) and a sample of adolescent NF1 - participants (N = 43). Whole brain comparisons demonstrated that during working memory conditions NF1 participants have greater connectivity in left posterior parietal regions, particularly converging at the postcentral gyrus. Comparison of communication between functional networks demonstrated that NF1 participants have increased connectivity between visual, sensorimotor, dorsal attention and limbic networks. Individual connections were weaker in NF1 participants across the brain, and we found reduced connectivity between control, dorsal attention and default networks in NF1. Furthermore, connectivity strength in these networks was predictive of accuracy and response time in NF1 participants during the task performance. Finally, graph theory analysis showed that working memory demands evoked reorganisation towards greater assortativity in NF1 participants, which was predictive of poorer accuracy and accuracy-speed trade-off. These findings highlight that NF1 participants' working memory deficits emerge from reduced engagement of executive processes, and NF1 participants demonstrate coping mechanisms such as enhanced sensorimotor processing and network reorganisation towards greater segregation, that is however detrimental to cognitive performance.