The relationship between radiotherapy dose and cognitive outcomes in functional brain network hubs of glioma patients with predominantly left frontal lobe lesions

Background
Emerging evidence suggests that cognitive dysfunction may result from damage to the brain's functional network. This study explores the dose-dependent susceptibility of functional hubs to radiotherapy (RT) and associations with cognitive outcomes.

Methods
Attention, language, memory, motor, and executive functioning were assessed >= 1-year post-radiotherapy in 39 WHO grade 2 or 3 glioma patients with lesions predominantly located in the left frontal lobe and 50 matched healthy controls. Using resting-state functional imaging, weighted functional graphs were constructed for each participant, identifying hubs through graph measures. Linear regression models and Spearman's rho correlations assessed associations between mean RT dose per region and cognitive domains.

Results
Higher RT doses to the left fusiform and inferior temporal gyri were linked to memory impairment (r(37) >= -0.565, PFDR <= 0.026), while poorer language outcomes were associated with higher doses to the left pars opercularis, rostral middle frontal gyrus, and caudate (r(37) >= -0.510, PFDR <= .040). Attention deficits were linked to higher doses to the left posterior cingulate, precentral, supramarginal, and postcentral gyrus ((37) >= -0.499, PFDR <= .040), with the left postcentral gyrus also associated with executive dysfunction (r(37) = -0.526, PFDR = .029). Significant correlations between RT dose and cognitive outcomes were more frequent in hubs than in non-hubs (50% vs. 12%, P = .005) and exclusively found in left-sided regions.

Conclusions
RT seems to adversely affect left-sided functional hubs in a dose-dependent manner in glioma patients, which may contribute to cognitive dysfunction. Protecting these regions from the dose may potentially mitigate cognitive side effects in glioma patients. However, since most lesions were located in the left hemisphere and baseline testing was unavailable, a potential effect of tumor location cannot be entirely ruled out. Radiation therapy is often used to treat brain tumors, but can sometimes lead to problems with thinking and memory. The authors of this study wanted to see if higher doses of radiation to certain areas of the brain were linked to worse cognitive outcomes. To do this, they looked at 39 patients with a glioma (a type of brain tumor) who had received radiation therapy and compared their thinking, memory, language, and motor skills to 50 healthy individuals. Their study found that higher doses of radiation to specific left-sided brain regions were linked to worse memory, language, attention, and other thinking skills.