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

Charlotte Sleurs; Sandra Jacobs; Serena J Counsell; Daan Christiaens; J-Donald Tournier; Stefan Sunaert; Karen Van Beek; Anne Uyttebroeck; Sabine Deprez; Dafnis Batalle; Jurgen Lemiere

doi:10.1016/j.radonc.2021.05.028

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

Charlotte Sleurs, Sandra Jacobs, Serena J Counsell, Daan Christiaens, J-Donald Tournier, Stefan Sunaert, Karen Van Beek, Anne Uyttebroeck, Sabine Deprez, Dafnis Batalle, Jurgen Lemiere

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Abstract

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 astrocytoma (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 supratentorial 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 dissociated macro- from microstructural changes, which were encountered in in infratentorial versus supratentorial 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.

Original language	English
Pages (from-to)	118-125
Number of pages	8
Journal	Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Volume	161
Early online date	4 Jun 2021
DOIs	https://doi.org/10.1016/j.radonc.2021.05.028
Publication status	Published - 1 Aug 2021

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10.1016/j.radonc.2021.05.028

Brain network hubs_SLEURS_Publishedonline4June2021_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 13 MBLicence: CC BY-NC-ND

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Sleurs, C., Jacobs, S., Counsell, S. J., Christiaens, D., Tournier, J.-D., Sunaert, S., Van Beek, K., Uyttebroeck, A., Deprez, S., Batalle, D., & Lemiere, J. (2021). Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 161, 118-125. https://doi.org/10.1016/j.radonc.2021.05.028

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title = "Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors",

abstract = "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 astrocytoma (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 supratentorial 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 dissociated macro- from microstructural changes, which were encountered in in infratentorial versus supratentorial 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.",

author = "Charlotte Sleurs and Sandra Jacobs and Counsell, {Serena J} and Daan Christiaens and J-Donald Tournier and Stefan Sunaert and {Van Beek}, Karen and Anne Uyttebroeck and Sabine Deprez and Dafnis Batalle and Jurgen Lemiere",

note = "Funding Information: We are grateful to Ron Peeters for his assistance during the MRI scanning sessions. We also thank Ellen Turelinckx and Lissa Maes for their help with acquisitions of the included neuropsychological assessments. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = aug,

day = "1",

doi = "10.1016/j.radonc.2021.05.028",

language = "English",

volume = "161",

pages = "118--125",

journal = "Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Sleurs, C, Jacobs, S, Counsell, SJ , Christiaens, D , Tournier, J-D, Sunaert, S, Van Beek, K, Uyttebroeck, A, Deprez, S, Batalle, D & Lemiere, J 2021, 'Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors', Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, vol. 161, pp. 118-125. https://doi.org/10.1016/j.radonc.2021.05.028

TY - JOUR

T1 - Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors

AU - Sleurs, Charlotte

AU - Jacobs, Sandra

AU - Counsell, Serena J

AU - Christiaens, Daan

AU - Tournier, J-Donald

AU - Sunaert, Stefan

AU - Van Beek, Karen

AU - Uyttebroeck, Anne

AU - Deprez, Sabine

AU - Batalle, Dafnis

AU - Lemiere, Jurgen

N1 - Funding Information: We are grateful to Ron Peeters for his assistance during the MRI scanning sessions. We also thank Ellen Turelinckx and Lissa Maes for their help with acquisitions of the included neuropsychological assessments. Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8/1

Y1 - 2021/8/1

N2 - 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 astrocytoma (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 supratentorial 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 dissociated macro- from microstructural changes, which were encountered in in infratentorial versus supratentorial 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.

AB - 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 astrocytoma (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 supratentorial 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 dissociated macro- from microstructural changes, which were encountered in in infratentorial versus supratentorial 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.

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U2 - 10.1016/j.radonc.2021.05.028

DO - 10.1016/j.radonc.2021.05.028

M3 - Article

C2 - 34102233

SN - 0167-8140

VL - 161

SP - 118

EP - 125

JO - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

ER -

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

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