Brain Functional Connectivity as a Mediator Between Hematological Metrics and Cognitive Decline in Children With
Shumin Xu1, Yi Zheng2, Yaowen Li1
1Department of Radiology, Shenzhen Children's Hospital, Shenzhen, China.
Insights
Children with Beta-thalassemia major (β-TM) exhibit impaired cognitive function due to altered brain connectivity. Hematological factors like hemoglobin levels indirectly impact cognition by affecting these neural networks.
Area of Science:
- Neuroscience
- Pediatric Hematology
- Cognitive Science
Background:
- Beta-thalassemia major (β-TM) is a genetic blood disorder requiring lifelong transfusions.
- Cognitive deficits are increasingly recognized in children with β-TM, but the underlying neural mechanisms remain unclear.
Purpose of the Study:
- To identify functional brain connectivity patterns linked to cognitive performance in children with β-TM.
- To investigate if hematological factors mediate the relationship between β-TM and cognitive function via brain connectivity.
Main Methods:
- Resting-state fMRI was used to analyze functional brain connectivity in 25 children with β-TM and 35 healthy controls.
- Network-based statistics (NBS) and connectome-based predictive modeling (CPM) were employed to compare connectivity and predict cognitive scores (Wechsler Intelligence Scale).
- Mediation analyses examined the influence of hemoglobin and red blood cell distribution width on cognition through functional connectivity.
Main Results:
- Children with β-TM showed lower cognitive scores and disrupted functional connectivity in cerebellar, motor, and temporal networks compared to controls.
- CPM successfully predicted cognitive scores using a network signature overlapping with NBS findings.
- Hemoglobin and red blood cell distribution width fully mediated the effect of β-TM on cognitive scores through altered brain connectivity.
Conclusions:
- Hematological abnormalities in β-TM contribute to cognitive impairment by disrupting functional brain networks.
- Functional connectivity patterns identified by CPM may serve as early biomarkers for cognitive vulnerability in β-TM.
- Findings suggest potential for targeted monitoring and interventions for cognitive deficits in pediatric β-TM.
Purpose:
This study aimed to identify functional brain connectivity patterns associated with cognitive performance in Beta-thalassemia major (β-TM) children and to determine whether hematological factors influence cognition indirectly through alterations in connectivity.
Method:
We recruited 25 children with β-TM and 35 age-matched healthy controls. Cognitive performance was assessed using the Wechsler Intelligence Scale (WIS). Resting-state functional MRI data were processed to construct whole-brain functional connectivity matrices. We applied network-based statistics (NBS) to compare connectivity differences between groups and connectome-based predictive modeling (CPM) with cross-validation to predict cognitive scores. Mediation analyses were further conducted to test whether hematological metrics (hemoglobin level, red blood cell distribution width) impacted cognition through functional connectivity.
Finding:
Compared to controls, β-TM children showed significantly reduced WIS scores and widespread disruptions in functional connectivity, particularly in cerebellar, motor, and temporal networks. The CPM approach identified a predictive network that largely overlapped with the NBS-derived network and robustly predicted WIS scores. Mediation analysis revealed that hemoglobin and red blood cell distribution width influenced cognitive scores indirectly through altered connectivity, indicating a full mediation effect.
Conclusion:
This study provides evidence that hematological abnormalities in β-TM children impair cognitive performance via their impact on functional brain networks. Functional connectivity signatures derived from CPM may serve as early neuromarkers of cognitive vulnerability and could inform future monitoring and intervention strategies in this population.
