Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention

Abstract OBJECTIVE To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors. METHODS Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/. RESULTS APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p<0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p<5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing. CONCLUSION Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.

Download Full-text

NCOG-71. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.609 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii145-ii145

Author(s):

Cassie Kline ◽

Schuyler Stoller ◽

Lennox Byer ◽

Caleb Edwards ◽

Rachna Prasad ◽

...

Keyword(s):

Brain Tumor ◽

Cortical Thickness ◽

Brain Volume ◽

Pediatric Brain Tumor ◽

Volumetric Analysis ◽

Small Sample ◽

Psychomotor Function ◽

Gene Set ◽

Genome Wide ◽

Pediatric Brain

Abstract OBJECTIVE To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors. METHODS Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/. RESULTS APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p< 0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p< 5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing. CONCLUSION Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.

Download Full-text

Beyond the brain: Socioeconomic status and race in pediatric brain tumor survivorship

Neuro-Oncology ◽

10.1093/neuonc/noab079 ◽

2021 ◽

Author(s):

Derek S Tsang ◽

Fiona Schulte

Keyword(s):

Socioeconomic Status ◽

Brain Tumor ◽

Pediatric Brain Tumor ◽

Pediatric Brain ◽

The Brain

Download Full-text

OMIC-02. COGNITIVE DEFICITS AND ALTERED FUNCTIONAL BRAIN NETWORK ORGANIZATION IN PEDIATRIC BRAIN TUMOR PATIENTS

Neuro-Oncology ◽

10.1093/neuonc/noab090.149 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i37-i37

Author(s):

Benjamin Seitzman ◽

Hari Anandarajah ◽

Alana McMichael ◽

Hongjie Gu ◽

Dennis Barbour ◽

...

Keyword(s):

Brain Tumor ◽

Cognitive Performance ◽

Pediatric Brain Tumor ◽

Functional Network ◽

Network Organization ◽

Tumor Patients ◽

Functional Brain Network ◽

Pediatric Brain ◽

Insight Into

Abstract Pediatric brain tumor survivors experience significant cognitive sequelae from their diagnosis and treatment. The exact mechanisms of cognitive injury are poorly understood, and validated predictors of long-term cognitive outcome are lacking. Large-scale, distributed brain systems provide a window into brain organization and function that may yield insight into these mechanisms and outcomes. We evaluated functional network architecture, cognitive performance, and brain-behavior relationships in pediatric brain tumor patients. Patients ages 8–18 years old with diagnosis of a brain tumor underwent awake resting state functional Magnetic Resonance Imaging during regularly scheduled clinical visits and were tested with the National Institutes of Health Toolbox Cognition Battery. Age- and sex-matched typically developing children were used as controls. We observed that functional network organization was significantly altered in patients compared to controls (p < 0.001), with the integrity of the dorsal attention network particularly affected (p < 0.0001). Moreover, patients demonstrated significant impairments in multiple domains of cognitive performance, including attention (p < 0.0001). Finally, a significant amount of variance (R squared = 0.52, F = 3.2, p < 0.05) of age-adjusted total composite scores from the Toolbox was explained by changes in segregation between the dorsal attention and default mode networks. Our results suggest that changes in functional network organization may provide insight into long-term changes in cognitive function in pediatric brain tumor patients.

Download Full-text