The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor.

in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology by Eloïse Baudou, Patrice Peran, Fatima Tensaouti, Germain Arribarat, Jérémie Pariente, Nicolas Courbieres, Lisa Pollidoro, Anne-Isabelle Bertozzi, Marion Gambart, Annick Sevely, Margaux Roques, Anne Ducassou, Jérémy Danna, Jessica Tallet, Christelle Dufour, Yves Chaix, Anne Laprie

TLDR

  • The study looked at how radiation therapy affects the brain's memory circuits in children with a type of brain tumor called posterior fossa tumor (PFT). The researchers used a special type of MRI called resting-state functional magnetic resonance imaging (rs-fMRI) to see how the brain's memory circuits were connected at rest. They found that irradiated PFT survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. The researchers also found that the performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients.

Abstract

Memory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI). A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. We manually contoured main structures involved in memory to explore connectivity at rest in a seed-to-voxel analysis. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. The results of this study highlight that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures.

Overview

  • The study explores the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI).
  • A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. The primary objective of the study is to investigate the long-term impact of radiotherapy on brain connectivity in neural circuits involved in memory after pediatric PFT and to identify the specific radiation-dose effect in supratentorial structures.

Comparative Analysis & Findings

  • The study found that irradiated PFT survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients.

Implications and Future Directions

  • The study highlights that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures. The findings suggest that irradiation may alter the neural circuits involved in memory, leading to impairments in episodic and procedural memory. Future research should investigate the long-term effects of irradiation on memory and other cognitive domains in pediatric brain tumor survivors. The study also highlights the importance of using rs-fMRI to assess brain connectivity in pediatric brain tumor survivors and to identify the specific radiation-dose effect on neural circuits involved in memory.
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