Grant Number:	1R15CA271450-01 Interpret this number
Primary Investigator:	Malloy, Elizabeth
Organization:	American University
Project Title:	Effects of Age and Lesion Location on Motor, Behavioral and Cognitive Outcomes in Pediatric Posterior Fossa Tumors
Fiscal Year:	2022

PROJECT SUMMARY Sixty percent of childhood brain tumors are located in the posterior fossa, which includes the cerebellum. Children with developmental cerebellar damage are at an increased risk for a range of adverse outcomes, including higher rates of autism diagnoses and long term cognitive and academic challenges. Traditionally considered a motor structure, extensive evidence now links the cerebellum to various cognitive and behavioral functions, and atypical cerebellar structure and function has been reported in multiple neurodevelopmental and psychiatric disorders. A key feature of cerebellar neuroanatomy is the existence of functional subregions that support sensorimotor and multiple non-motor functions. This leads to the hypothesis that motor, cognitive, and behavioral outcomes should be predictable based on lesion location. While our previous lesion-symptom mapping studies have shown this to be the case in adult cerebellar stroke patients, there are limited studies linking location of lesion to outcomes in pediatric populations. Further, we and others have proposed that the learning mechanisms subserved by the cerebellum are critical during development, leading to the hypothesis that cerebellar damage at a younger age would be associated with worse long-term outcomes than damage in adulthood. Based on findings from preterm infants with perinatal cerebellar damage, early cerebellar damage could lead to the atypical development of specific cortical regions to which the cerebellum interconnects in a lesion location-dependent manner. To test these hypotheses, we propose to analyze pre-existing structural imaging and neuropsychological data from ~70 children with a history of pediatric cerebellar tumor. We will conduct multivariate voxel-based lesion-symptom mapping to determine the relationship between lesion location and various motor, cognitive, and behavioral outcome variables; we will specifically examine the impact of age at tumor diagnosis and treatment protocols on these outcomes; and, in patients with longitudinal data, we will examine the impact of age of tumor diagnosis and lesion location on long term outcomes and whole-brain grey and white matter development. The goal of this research is to improve outcome prediction and educational planning in pediatric cerebellar patients. A better understanding of the mechanism(s) by which early cerebellar damage impacts lifelong motor, cognitive, and behavioral development may lead to new interventions to enhance behavioral and neural outcomes for these children.





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