Brain functional connectivity as a mediator between hematological metrics and cognitive decline in children with beta-thalassemia major

Children with beta-thalassemia major ({beta} -TM) are at risk of cognitive impairment, particularly in learning and memory. While cognitive deficits in the general population have been extensively studied, brain-based predictors for {beta}-TM children remain unexplored. This study used connectome-based predictive modeling (CPM) to examine whole-brain functional connectivity in 60 participants to predict cognitive performance. {beta}-TM children showed impaired cognitive abilities, as evidenced by lower Wechsler Intelligence Scale scores compared to controls. The identified brain regions, though not typically linked to cognitive performances, exhibited functional connectivity patterns associated with {beta}-TM, as confirmed by network-based statistics. Correlations between task performance, functional connectivity identified by the CPM, and hematological metrics were also examined. Significant correlations were found between the strength of functional network identified by CPM and hematological metrics, particularly hemoglobin levels and red blood cell distribution width. The study demonstrates that hematological factors influence cognitive performance indirectly through specific functional connectivity, providing new insights into the neural underpinnings of cognitive deficits in children with beta-thalassemia major.