Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors. 2021

Charlotte Sleurs, and Sandra Jacobs, and Serena J Counsell, and Daan Christiaens, and J-Donald Tournier, and Stefan Sunaert, and Karen Van Beek, and Anne Uyttebroeck, and Sabine Deprez, and Dafnis Batalle, and Jurgen Lemiere
Department of Oncology, KU Leuven, Belgium. Electronic address: charlotte.sleurs@kuleuven.be.

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. 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. 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. 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.

UI MeSH Term Description Entries
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002528 Cerebellar Neoplasms Primary or metastatic neoplasms of the CEREBELLUM. Tumors in this location frequently present with ATAXIA or signs of INTRACRANIAL HYPERTENSION due to obstruction of the fourth ventricle. Common primary cerebellar tumors include fibrillary ASTROCYTOMA and cerebellar HEMANGIOBLASTOMA. The cerebellum is a relatively common site for tumor metastases from the lung, breast, and other distant organs. (From Okazaki & Scheithauer, Atlas of Neuropathology, 1988, p86 and p141) Benign Cerebellar Neoplasms,Cerebellar Cancer,Malignant Cerebellar Neoplasms,Cerebellar Neoplasms, Benign,Cerebellar Neoplasms, Malignant,Cerebellar Neoplasms, Primary,Cerebellar Tumors,Neoplasms, Cerebellar,Neoplasms, Cerebellar, Benign,Neoplasms, Cerebellar, Malignant,Neoplasms, Cerebellar, Primary,Primary Neoplasms, Cerebellum,Benign Cerebellar Neoplasm,Cancer, Cerebellar,Cerebellar Cancers,Cerebellar Neoplasm,Cerebellar Neoplasm, Benign,Cerebellar Neoplasm, Malignant,Cerebellar Neoplasm, Primary,Cerebellar Tumor,Cerebellum Primary Neoplasm,Cerebellum Primary Neoplasms,Malignant Cerebellar Neoplasm,Neoplasm, Benign Cerebellar,Neoplasm, Cerebellar,Neoplasm, Cerebellum Primary,Neoplasm, Malignant Cerebellar,Primary Cerebellar Neoplasm,Primary Cerebellar Neoplasms,Primary Neoplasm, Cerebellum,Tumor, Cerebellar
D003071 Cognition Intellectual or mental process whereby an organism obtains knowledge. Cognitive Function,Cognitions,Cognitive Functions,Function, Cognitive,Functions, Cognitive
D003430 Cross-Sectional Studies Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time. Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D015192 Infratentorial Neoplasms Intracranial tumors originating in the region of the brain inferior to the TENTORIUM CEREBELLI, which contains the cerebellum, FOURTH VENTRICLE; CEREBELLOPONTINE ANGLE; BRAIN STEM, and related structures. Primary tumors of this region are more frequent in children, and may present with ATAXIA; CRANIAL NERVE DISEASES; vomiting; HEADACHE; HYDROCEPHALUS; or other signs of neurologic dysfunction. Relatively frequent histologic subtypes include TERATOMA; MEDULLOBLASTOMA; GLIOBLASTOMA; ASTROCYTOMA; EPENDYMOMA; CRANIOPHARYNGIOMA; and choroid plexus papilloma (PAPILLOMA, CHOROID PLEXUS). Infratentorial Tumors,Posterior Fossa Neoplasms,Benign Infratentorial Neoplasms,Infratentorial Cancer,Infratentorial Neoplasms, Benign,Infratentorial Neoplasms, Malignant,Malignant Infratentorial Neoplasms,Neoplasms, Infratentorial,Neoplasms, Posterior Fossa,Posterior Fossa Tumors,Benign Infratentorial Neoplasm,Cancer, Infratentorial,Infratentorial Cancers,Infratentorial Neoplasm,Infratentorial Neoplasm, Benign,Infratentorial Neoplasm, Malignant,Infratentorial Tumor,Malignant Infratentorial Neoplasm,Neoplasm, Benign Infratentorial,Neoplasm, Infratentorial,Neoplasm, Malignant Infratentorial,Neoplasm, Posterior Fossa,Neoplasms, Malignant Infratentorial,Posterior Fossa Neoplasm,Posterior Fossa Tumor,Tumor, Infratentorial,Tumor, Posterior Fossa
D017741 Survivors Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events. Long-Term Survivors,Long Term Survivors,Long-Term Survivor,Survivor,Survivor, Long-Term,Survivors, Long-Term

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