Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors

Background: Childhood infratentorial tumor patients frequently suffer from long-term cognitive deficits. As each constituent of their treatment can lead to neurotoxicity, cascade effects can lead to profound reorganization of the underlying brain network, the so-called 'connectome'. However, to date, few studies have assessed the relationship between brain network topology, the functional role of network hubs (i.e. highly connected regions), and neurocognitive outcomes in adult survivors of childhood infratentorial tumors. Methods: In this cross-sectional study, childhood infratentorial tumor survivors (n = 21: pilocytic astro-cytoma (n = 8), ependymoma (n = 1) and medulloblastoma (n = 12)) and healthy controls (n = 21) were recruited. Using multishell diffusion-weighted MRI, microstructural organization and topology of supra-tentorial white matter was investigated; using a voxel-based approach, a fixel-based analysis, and a graph theoretical approach. In addition, neurocognitive subscales of the WAIS-IV intelligence test, and their relationship with nodal strength and network efficiency metrics were assessed. Results: Similar to earlier studies, we observed widespread decreases in fractional anisotropy (FA) in patients compared to controls, based on voxel-based analyses. In addition, the fixel-based analyses dis-sociated macro-from microstructural changes, which were encountered in in infratentorial versus supra-tentorial brain areas, respectively. Finally, regional reorganization (i.e. differences in local efficiency) occurred mainly in hubs, which suggests a specific vulnerability of these areas. These hubs were not only mostly affected, but also most strongly correlated with the intelligence subscales. Conclusion: This study suggests that network hubs are functionally important for intellectual outcomes in infratentorial tumor survivors. Furthermore, these regions could be the primary targets of treatment toxicity. Validation of this specific hypothesis in larger samples is required. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 161 (2021) 118-125

Automated summary

The study revealed significant changes in the brain network structure of childhood infratentorial tumor survivors, especially in the network hubs. These hubs were not only most affected, but also most strongly correlated with intellectual outcomes.