Brain tumor (BT) patients often experience reduced cognitive abilities and disrupted adaptive functioning before and after treatment. An innovative approach to understanding the underlying brain networks associated with these outcomes has been to study the brain's functional connectivity (FC), the spatially distributed and temporally correlated activity throughout the brain, and how it can be affected by a tumor. The present review synthesized the extant BT FC literature that utilizes functional magnetic resonance imaging to study FC strength of commonly observed networks during rest and task. A systematic review of English articles using PubMed was conducted. Search terms included brain tumor OR glioma AND functional connectivity, independent component analysis, ICA, psychophysiological interaction, OR PPI. Studies in which participants were diagnosed with BTs as adults that evaluated specific networks of interest using independent component analysis or seed-based component analysis were included. Twenty-five studies met inclusion criteria. BT patients often presented with decreases in FC strength within well-established networks and increases in atypical FC patterns. Network differences were tumor adjacent and distal, and left hemisphere tumors generally had a greater impact on FC. FC alterations often correlated with behavioral or cognitive outcomes when assessed. Overall, BTs appear to lead to various alterations in FC across different functional networks, and the most common change is a decrease in expected FC strength. More longitudinal studies are needed to determine the time course of network alterations across treatment and recovery, the role of medical treatments in BT survivors' FC, and the potential of FC patterns as biomarkers of cognitive outcomes.

Childhood brain tumors and related treatments disrupt the developing brain and have a cascading impact on core cognitive skills and intellectual (intelligence quotient [IQ]) and academic achievement outcomes. Theoretical models for this cascade have been developed based on the literature, but no studies thus far have empirically evaluated the models. The current study aimed to empirically test the two extant models and generate a new data-driven model of the relationships among neurodevelopmental risk factors, core cognitive skills (i.e., processing speed, attention span, working memory), and IQ and achievement outcomes. Fifty-seven adult survivors of childhood brain tumors and fifty-seven demographically matched neurotypical individuals were included in the current study. The average age at brain tumor diagnosis was 8 years, and the average time since diagnosis was 17 years. Three a priori path models tested the hypothesized relationships among variables. Results of the path analyses revealed that the hybrid model best fit the data for both survivors and controls based on all statistical criteria. For survivors, processing speed was the core cognitive skill most widely associated with neurodevelopmental risk factors and outcomes. However, working memory and attention span also had unique contributions to IQ and academic achievement. Processing speed appears to be the central cognitive skill that disrupts the other core cognitive skills of attention span and working memory, and all three make a unique contribution to IQ and academic achievement. This is best demonstrated by a novel neurodevelopmental model that combines components of two earlier untested theoretical models.

Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors.

White matter disruptions have been identified in individuals with congenital heart disease (CHD). However, no specific theory-driven relationships between microstructural white matter disruptions and cognition have been established in CHD. We conducted a two-part study. First, we identified significant differences in fractional anisotropy (FA) of emerging adults with CHD using Tract-Based Spatial Statistics (TBSS). TBSS analyses between 22 participants with CHD and 18 demographically similar controls identified five regions of normal appearing white matter with significantly lower FA in CHD, and two higher. Next, two regions of lower FA in CHD were selected to examine theory-driven differential relationships with cognition: voxels along the left uncinate fasciculus (UF; a tract theorized to contribute to verbal memory) and voxels along the right middle cerebellar peduncle (MCP; a tract previously linked to attention). In CHD, a significant positive correlation between UF FA and memory was found,r(20)=.42,p=.049 (uncorrected). There was no correlation between UF and auditory attention span. A positive correlation between MCP FA and auditory attention span was found,r(20)=.47,p=.027 (uncorrected). There was no correlation between MCP and memory. In controls, no significant relationships were identified. These results are consistent with previous literature demonstrating lower FA in younger CHD samples, and provide novel evidence for disrupted white matter integrity in emerging adults with CHD. Furthermore, a correlational double dissociation established distinct white matter circuitry (UF and MCP) and differential cognitive correlates (memory and attention span, respectively) in young adults with CHD. (JINS, 2015,21, 22–33)