Associations Between Trail-Making Test Black and White Performance and Gray Matter Volume in Community-Dwelling Cognitively Healthy Adults Aged 40 to 80 Years.

The Trail Making Test (TMT) is a widely used neuropsychological tool to assess processing speed (Part A) and executive function (Part B). However, the neuroanatomical substrates underlying its Black & White variant (TMT-B&W) and the influence of demographic factors remain poorly understood. This study aimed to identify gray matter (GM) correlates of TMT-B&W performance across unadjusted and covariate-adjusted models in cognitively healthy adults. In this cross-sectional study, 87 participants (40-80 years) underwent structural magnetic resonance imaging (MRI) and completed TMT-B&W. Whole-brain voxel-based morphometry (VBM) was conducted using FreeSurfer for preprocessing and Computational Anatomy Toolbox (CAT12)/Statistical Parametric Mapping (SPM12) for analysis. Two voxel-wise regression models (unadjusted and adjusted for age, education, gender, and total intracranial volume (TICV)) assessed GM associations with TMT-B&W-A-B performance. Statistical thresholds were voxel-level < 0.001 (uncorrected) and cluster-level Family-Wise Error (FWE) correction ( < 0.001). In unadjusted models, TMT-B&W-A performance correlated with GM reductions in the right orbitofrontal cortex (T = 42.64, equivk = 515.60, representing peak voxel level T-statistic and cluster size in voxels), while TMT-B&W-B linked to the right insular cortex (T = 50.65, equivk = 515.50). After adjustment, both tasks converged on the left thalamus (TMT-A: T = 8.05, equivk = 594; TMT-B: T = 8.11, equivk = 621), with TMT-B&W-B showing a denser thalamic cluster. Demographic covariates attenuated cortical associations, revealing thalamic integration as a shared mechanism. The thalamus emerges as a critical hub for TMT-B&W performance when accounting for demographic variation, while distinct cortical regions mediate task-specific demands in unadjusted models. These findings support the TMT-B&W as a practical, low-cost neurobehavioral marker of brain integrity in older populations.