| Description: |
Objective Neuropsychological symptoms in brain tumor patients are often incompletely explained by tumor variables and may be more directly related to changes in large-scale functional network connectivity. Here we examine these relationships. Methods Fifty-one participants underwent pre-operative resting-state functional MRIs and three neuropsychological tests—Trail Making Test-Part-B (TMT-B), WAIS-IV Digit-Span Sequencing (WAIS-DS), and Controlled Oral Word Association Test (COWAT). Within-network functional connectivity of the central executive (CEN), default mode (DMN), language (LANG), and salience (SN) networks were compared to healthy controls. Spearman correlations (ρ) were performed between neuropsychological z-scores, abnormal within-network connectivity, and tumor variables. Exploratory, statistical mediation analyses then evaluated if relevant tumor variables mediated neuropsychological performance via functional connectivity. Results Significant correlations included: (1) WAIS-DS performance to lesional-SN (ρ = 0.53, P = .006), lesional-sided-CEN (ρ = 0.42, P = .023), and right-SN (ρ = 0.42, P = .023) connectivity; (2) COWAT performance to right-SN (ρ = 0.50, P = .012), lesional-SN connectivity (ρ = 0.45, P = .017), and lesion laterality (ρ = 0.47, P = .017); and (3) TMT-B to lesional-LANG (ρ = 0.46, P = .017), right-CEN (ρ = 0.45, P = .017), and bilateral-LANG (ρ = 0.42, P = .024) connectivity. Mediation analyses revealed the effect of: (1) lesion laterality on TMT-B was fully mediated via right-CEN connectivity (path a*b; β = 0.273 [0.064, 0.478]); (2) IDH-status on WAIS-DS was fully mediated via lesional-CEN connectivity (path a*b; β = 0.251 [0.015, 0.588]); and (3) lesion laterality on COWAT was partially mediated via right-SN connectivity (path a*b; β = 0.333 [0.004–0.72]). Conclusions Our data support the hypothesis that functional network connectivity may explain some neuropsychological heterogeneity across otherwise anatomically and oncologically similar cases. Notably, more abnormal ... |