Association between subcortical vascular lesion location and cognition: a voxel-based and tract-based lesion-symptom mapping study. The SMART-MR study

Abstract

Introduction: Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden.

Methods: Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning.

Results: Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden.

Conclusion: These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment.

Figure 1. Segmentation of lesions within a specific white matter tract.

The native T2 FLAIR (A) and T1 (B) sequences were used for segmentation of white matter lesions (WMLs) and lacunar lesions (LLs). The native T1 sequence was subsequently registered to MNI space followed by co-registration of the lesion maps using the same warp field. C: WMLs (blue) and LLs (red) projected on the registered T1 sequence. D: WMLs (blue) and LLs (red) projected on the MNI template. The anterior thalamic radiation is depicted in green. Regional lesion volumes within specific white matter tracts, in this case the anterior thalamic radiation, were associated with cognitive functioning using a linear regression model.

Figure 2. Frequency of white matter lesions.

Voxels with white matter lesion (WML) in at least 5 patients are projected on a 2 mm MNI-152 template (Z and Y coordinates are provided). Bar indicates the number of patients with WML for each voxel.

Figure 3. Voxel-based lesion-symptom mapping results.

A: map of the correlation (t-statistic) between a lesion in each voxel and executive functioning. Voxels exceeding the false discovery rate threshold (q = 0.05 resulting in a threshold of t = 2.4) are rendered in red corresponding with a t-value >2.4, while non-significant voxels are rendered on a scale from blue to green corresponding with t-values ranging from 0 to 2.4. Results were adjusted for age, sex, level of education and performance on the Dutch Adult Reading Test. B and C: same analysis as A. Voxels exceeding the false discovery rate threshold and the superior longitudinal fasciculus (yellow) and anterior thalamic radiation (green) are depicted.