Exploring biomarkers of processing speed and executive function: The role of the anterior thalamic radiations

Abstract

Introduction: Processing speed and executive function are often impaired after stroke and in typical aging. However, there are no reliable neurological markers of these cognitive impairments. The trail making test (TMT) is a common index of processing speed and executive function. Here, we tested candidate MRI markers of TMT performance in a cohort of older adults and individuals with chronic stroke. Methods: In 61 older adults and 32 individuals with chronic stroke, we indexed white matter structure with region-specific lesion load (of white matter hyperintensities (WMHs) and stroke lesions) and diffusion tensor imaging (DTI) from four regions related to TMT performance: the anterior thalamic radiations (ATR), superior longitudinal fasciculus (SLF), forceps minor, and cholinergic pathways. Regression modelling was used to identify the marker(s) that explained the most variance in TMT performance. Results: DTI metrics of the ATR related to processing speed in both the older adult (TMT A: β = -3.431, p < 0.001) and chronic stroke (TMT A: β = 11.282, p < 0.001) groups. In the chronic stroke group executive function was best predicted by a combination of ATR and forceps minor DTI metrics (TMT B: adjustedR2 = 0.438, p < 0.001); no significant predictors of executive function (TMT B) emerged in the older adult group. No imaging metrics related to set shifting (TMT B-A). Regional DTI metrics predicted TMT performance above and beyond whole-brain stroke and WMH volumes and removing whole-brain lesion volumes improved model fits. Conclusions: In this comprehensive assessment of candidate imaging markers, we demonstrate an association between ATR microstructure and processing speed and executive function performance. Regional DTI metrics provided better predictors of cognitive performance than whole-brain lesion volumes or regional lesion load, emphasizing the importance of lesion location in understanding cognition. We propose ATR DTI metrics as novel candidate imaging biomarker of post-stroke cognitive impairment.