The Impact of Covariates in Voxel-Wise Lesion-Symptom Mapping

Background: Voxel-wise lesion-symptom mapping (VLSM) is a statistical technique to infer the structure-function relationship in patients with cerebral strokes. Previous VLSM research suggests that it is important to adjust for various confounders such as lesion size to minimize the inflation of true effects. The aim of this work is to investigate the regional impact of covariates on true effects in VLSM. Methods: A total of 222 follow-up datasets of acute ischemic stroke patients with known NIH Stroke Scale (NIHSS) score at 48-h post-stroke were available for this study. Patient age, lesion volume, and follow-up imaging time were tested for multicollinearity using variance inflation factor analysis and used as covariates in VLSM analyses. Covariate importance maps were computed from the VLSM results by standardizing the beta coefficients of general linear models. Results: Covariates were found to have distinct regional importance with respect to lesion eloquence in the brain. Age has a relatively higher importance in the superior temporal gyrus, inferior parietal lobule, and in the pre- and post-central gyri. Volume explains more variability in the opercular area of the insula, inferior frontal gyrus, and caudate. Follow-up imaging time accounts for most of the variance in the globus pallidus, ventromedial- and dorsolateral putamen, dorsal caudate, pre-motor thalamus, and the dorsal insula. Conclusions: This is the first study investigating and revealing distinctive regional patterns of importance for covariates typically used in VLSM. These covariate importance maps can improve our understanding of the lesion-deficit relationships in patients and could prove valuable for patient-specific treatment and rehabilitation planning.