Fronto-limbic white matter microstructure, behavior, and emotion regulation in survivors of pediatric brain tumor

Area of Science:

• Neuroscience
• Pediatric Oncology
• Radiology

Background:

• Pediatric brain tumor survivors (PBTS) often experience emotional and behavioral challenges post-treatment.
• These difficulties may stem from tumor or treatment-related alterations in brain regions governing emotion regulation, particularly those with fronto-limbic connections.

Purpose of the Study:

• To investigate differences in emotional and behavioral functioning between PBTS and healthy controls (HCs).
• To assess white matter microstructure, specifically mean fractional anisotropy (mFA), in fronto-limbic tracts (cingulum bundle, inferior fronto-occipital fasciculus, uncinate fasciculus) in PBTS versus HCs.
• To determine if mFA mediates the relationship between group status and emotional/behavioral outcomes.

Main Methods:

• Diffusion tensor imaging (DTI) and tractography were used to quantify mFA in selected white matter tracts in 11 PBTS and 14 HCs (ages 8-16).
• Parental ratings assessed emotional and behavioral functioning.

Main Results:

• Caregivers reported significantly poorer behavioral regulation and higher internalizing and externalizing symptoms in PBTS compared to HCs.
• PBTS exhibited reduced mFA in bilateral cingulum bundle, inferior fronto-occipital fasciculus, and uncinate fasciculus compared to HCs.
• Across both groups, mFA in these tracts correlated with behavioral regulation and internalizing/externalizing symptoms, and mFA accounted for variance in the group-outcome relationship.

Conclusions:

• Reduced mFA in fronto-limbic tracts is associated with impaired behavioral regulation in PBTS.
• PBTS undergoing treatments known to affect white matter integrity may be particularly vulnerable.
• Further research with larger, longitudinal studies is needed to elucidate these relationships and consider specific tumor and treatment factors.