Higher order cognitive functions (attention and memory) performed by “association cortex” decline more compared to basic somatosensory defects performed by motor cortex to fractionated RT. Authors sought to evaluate the regional vulnerability subserving the higher order cognition to fractionated RT using Quantitative MRI. This retrospective single center study encompassed a cohort of 25 brain tumor patients treated using fractionated partial brain irradiation & underwent standard high-resolution volumetric MR protocol (T1-weighted; T2 FLAIR) pre-RT and one-year post-RT start (9-15 months). Semi-automated free surfer software was used to segment anatomic regions of the cerebral cortex for each patient. Mean Cortical thickness was measured for each region pre-RT and at one year. MRI voxels falling within 5mm of Gross tumor volume were excluded. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, two primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Radiation dose data were projected onto the pre-RT cortical surface using FreeSurfer, and mean radiation dose was also calculated for each cortical region. The relationship of mean radiation dose and mean cortical thickness change was assessed by univariate linear regression for all instances of right or left entorhinal cortex & primary cortex areas in the patient cohort. All “association cortex” regions of interest (entorhinal or inferior parietal) that received greater than 40 Gy mean dose were tested for significant cortical thickness change via Student’s t-test. Cortical thinning was significantly associated with mean radiation dose for the entorhinal cortex (p = 0.01) and inferior parietal cortex (p = 0.02), both association cortex ROIs. Primary cortex ROIs showed no significant cortical thinning regardless of whether they received a high (>40 Gy) or low (<20 Gy) radiation dose. In the whole-cortex analysis, regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (p≤0.002). Areas of cerebral cortex most vulnerable to radiation-related atrophy includes those performing higher-order cognition in brain "association areas ” thus leading to deficits in domains of memory, executive function, and attention.