Associations among diffusion tensor imaging and neurocognitive function in survivors of pediatric brain tumor: A pilot study.

The purpose of this study was to determine associations among neurocognitive outcomes and white matter integrity in the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and genu of the corpus callosum (gCC) in survivors of pediatric brain tumor and healthy controls (HCs). Eleven survivors (ages 8-16; >2 years post-treatment) and 14 HCs underwent MRI; diffusion tensor imaging tractography (DSI Studio) was used to assess white matter integrity. Participants completed neuropsychological assessment of overall cognitive ability, executive function, processing speed, divided attention, and memory. As previously reported, survivors performed significantly worse than HCs on measures of overall IQ, working memory, processing speed, and executive function (ps < .01), but not on measures of long-delay memory. Mean fractional anisotropy was significantly lower in survivors than HC in the right IFOF, left UF, and gCC (ps < .05). Correlations with the total sample revealed a number of significant positive associations among white matter tracts and scores on neurocognitive measures. Survivors show deficits on measures of cognitive function and decreased white matter integrity compared to HCs. Results revealed a more general pattern of associations among white matter pathways and neurocognitive outcomes than initially hypothesized. It is possible that survivors with diffuse pathology from treatment effects (i.e., hydrocephalus or posterior fossa syndrome) show more general decreases in cognitive functioning and white matter integrity. Additional research with a larger and more diverse group of survivors is needed to better understand white matter integrity and neurocognitive outcome associations in this population.

Fronto-limbic white matter microstructure, behavior, and emotion regulation in survivors of pediatric brain tumor.

PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.