Medulloblastoma is an embryonal tumor of the cerebellum, which is the most common malignant brain neoplasms in children. Survivors of medulloblastoma have an increased risk of neurocognitive impairments following tumor resection surgery. Supratentorial neurometabolic and structural changes have been reported in medulloblastoma patients. The associations between supratentorial brain structural changes and cognitive deficits, particularly in long-term medulloblastoma survivors, however, have not been systematically analyzed. This study aimed to establish supratentorial grey matter changes and their relation to profiles of long-term cognitive deficits in medulloblastoma survivors.

Twenty-two medulloblastoma survivors (>12 months after complete treatments) and twenty-one age-, sex-, and education-matched healthy controls underwent structural brain MRI and neuropsychological and intellectual assessments. Eight cognitive domains were examined, including attention, working memory, visuospatial function, language, episodic memory, executive function, abstract reasoning, and affect.  Supratentorial grey matter volume was examined using voxel-based morphometry.

Compared to healthy controls, patients showed impaired neurocognitive performance across all cognitive domains, with the exception of attention and episodic memory. Patients with cerebellar mutism syndrome (CMS) performed worse than patients without CMS on executive function. Neurocognitive performance was positively predicted by intelligence. Supratentorial grey matter changes were found in the bilateral thalamus and the right caudate. Significant associations were found between cerebral integrity and neurocognitive performance in attention, visuospatial function, working memory, abstract reasoning, and executive function. Notably, the left superior temporal gyrus emerged as a key region associated with multiple cognitive domains. Specifically, attention was associated with the left superior temporal gyrus. Visuospatial function was associated with the left postcentral gyrus and the right putamen and insular. Working memory was associated with the bilateral thalamus, the right superior temporal gyrus, lingual gyrus, and putamen. Abstract reasoning was associated the left superior temporal gyrus. Finally, executive function was associated with the left superior temporal gyrus and insular.

Our findings establish the profile of cognitive deficits in long-term medulloblastoma survivors, underscoring the lasting impact of the tumor and its treatments. Particularly, the association between supratentorial structural changes and cognitive deficits provides valuable insights into the neural underpinnings of these impairments. These findings underscore the importance of ongoing neuropsychological monitoring and intervention for medulloblastoma survivors, with a view to enhancing their quality of life and cognitive rehabilitation. The results also pave the way for future research to further elucidate the underlying mechanisms and potential therapeutic avenues for addressing the cognitive challenges faced by these patients.