Approximately 55% of all brain tumors in children are located in the posterior fossa with medulloblastoma being the most common form.¹ The current standard of care for pediatric medulloblastoma includes maximal surgical excision, risk-adapted cranial radiation therapy (CRT), and adjuvant chemotherapy which has achieved an overall survival of 75%.² Unfortunately, effective therapy is associated with neurocognitive deficits in the frontal lobe–mediated cognitive domains, such as working memory,^3,4 intelligence, academic performance,^5,6 processing speed, and attention⁴ in survivors. In an effort to more fully understand the association between CRT and neurocognitive deficits, this study assesses changes in structural connectivity of the central executive network (CEN) ^7-9 in response to CRT.MR scans of 30 medulloblastoma patients (Age at exam 11.2+5.2 years; 8 average-risk [23.4 Gy CRT], 22 high-risk [36.0 Gy CRT]) were used for this study. For each patient, two MR scans were performed, one Pre-CRT and one Post-CRT. Each MR scan consists of anatomic 3D T1 weighted imaging and diffusion tensor imaging (DTI, 30 directions, 2 averages, b=700). For each scan, the anatomic imaging set was processed using Freesurfer (surfer.nmr.mgh.harvard.edu/)¹⁰ to obtain the 20 brain structures (4 sub-cortical and 6 cortical for each hemisphere) included in the CEN. DTI processing was performed using the FSL FRMIB Toolbox (fsl.fmrib.ox.ac.uk/fsl/)¹¹. To establish a reproducible network graph for each exam, probabilistic fiber tracking was then performed using FSL with 500 permutations from each of the anatomic structures for the pathways identified in the CEN. The connection pathway between two nodes, which was the volume in image space that the connection fibers passed through, was extracted for each valid connection using a previously developed adaptation of the probabilistic fiber tracing technique.¹² The mean fractional anisotropy (FA), axial diffusivity (AX) and radial diffusivity (RAD) values of the connection pathway served as the quantitative measure for each edge and were evaluated at Pre-CRT and Post-CRT. Differences in metrics Pre-CRT and Post-CRT (Post-CRT – Pre-CRT) were tested using a paired T-test and differences for each risk-arm were tested using a Wilcoxon ranked sums test to determine if the differences were significantly different from zero. All tests were corrected for multiple comparisons using the false discovery rate (FDR) procedure.¹³Figure 1 demonstrates the full CEN model used in this study along with the identification of subnetworks within the CEN that were used for subsequent analyses. Results from the analysis comparing differences in DTI metrics of FA and AX Pre-CRT and Post-CRT for all 30 subjects for each of the subnetworks within the CEN are shown in Table 1. A negative delta value indicates a decrease in the metric during CRT. There was no significant change in the RAD metric across CRT. Due to the unbalanced distribution of subjects within the risk arms, we were unable to find any significant differences between the risk arms using a direct comparison. However, average-risk subjects demonstrated only 4 subnetworks with changes in FA that were significantly different from zero and none for AX, as shown in Table 2. Furthermore, high-risk subjects showed that half (6 of 12) subnetworks for FA and all subnetworks for AX were significantly different from zero (Table 2).Evaluation of the CEN model demonstrated significant changes in cerebral white matter due to CRT in children treated for medulloblastoma. The decreased FA and AX primarily involved connections to the basal ganglia. While the average-risk group was too small to reliably evaluate, the larger group of high-risk patients demonstrated that all subnetworks within the CEN demonstrated significant decreases in AX in response to CRT. Decreased AX may occur due to the accumulation of cellular debris, disordering of microtubule arrangement, and filament aggregation in acute axonal injury.¹⁴ These findings suggest significant reduction in the microstructural integrity within the CEN immediately after CRT in this population and support the use of the CEN model for evaluating changes in cerebral white matter early in therapy which could potentially be associated with later neurocognitive deficits.