Aberrant functional connectivity and Granger causality analysis in patients with β-thalassemia major

This study aimed to assess alterations in functional connectivity (FC) within brain networks in children and adolescents with β-TM major and to explore the intrinsic relationship between network changes and cognitive impairment. This prospective study recruited 70 patients with β-TM and 64 healthy controls. Cognitive function assessments using Montreal Cognitive Assessment (MoCA) and Modified Mini-Mental State Examination (MMMSE), and hematological parameters were collected. Region of interest (ROI)-to-ROI connectivity analysis was conducted to investigate the whole brain FC within and between resting-state networks. Granger causality analysis was utilized to evaluate the effective interactions among them. Patients exhibited significant cognitive impairment compared to controls. Key hematological indicators, such as serum ferritin, were not found to be correlated with cognitive function. Rs-fMRI revealed extensive reductions in functional connectivity, accompanied by several enhancements. These FCs’ alterations significantly correlated with cognitive deficits. Granger causality analysis further indicated effective information flow from these FCs. This study showed significant correlation of cognitive impairment with aberrant FC in brain networks and hematological parameters in patients with β-TM. These results should advance our understanding of the neural mechanism underlying β-TM-related cognitive dysfunction and may serve as potential neuroimaging biomarkers for cognitive functioning in this population.