Strategic infarct location for post-stroke cognitive impairment: A multivariate lesion-symptom mapping study

Abstract

Lesion location is an important determinant for post-stroke cognitive impairment. Although several 'strategic' brain regions have previously been identified, a comprehensive map of strategic brain regions for post-stroke cognitive impairment is lacking due to limitations in sample size and methodology. We aimed to determine strategic brain regions for post-stroke cognitive impairment by applying multivariate lesion-symptom mapping in a large cohort of 410 acute ischemic stroke patients. Montreal Cognitive Assessment at three to six months after stroke was used to assess global cognitive functioning and cognitive domains (memory, language, attention, executive and visuospatial function). The relation between infarct location and cognition was assessed in multivariate analyses at the voxel-level and the level of regions of interest using support vector regression. These two assumption-free analyses consistently identified the left angular gyrus, left basal ganglia structures and the white matter around the left basal ganglia as strategic structures for global cognitive impairment after stroke. A strategic network involving several overlapping and domain-specific cortical and subcortical structures was identified for each of the cognitive domains. Future studies should aim to develop even more comprehensive infarct location-based models for post-stroke cognitive impairment through multicenter studies including thousands of patients.

Keywords: Cognitive impairment; infarct location; ischemic stroke; multivariate lesion-symptom mapping; support vector regression.

Figure 1.

Lesion prevalence map (a) and lesion size topographies (b). (a) Voxels that are damaged in at least four patients are projected on the 1 mm MNI-152 template (Z coordinates: −33, −11, 0, 9, 17, 28, 40). Bar indicates the number of patients with a lesion for each voxel. (b) Lesion size topographies in ml for each voxel lesioned in at least four patients. Bar indicates the median lesion volume a patient would have, given that the specific voxel is lesioned. The lesion maps are shown in neurological convention (left is on the left).

Figure 2.

Results of multivariate lesion-symptom mapping. Voxel-wise associations between the presence of a lesion and cognitive functioning were determined using support vector regression (SVR-LSM). This multivariate approach assesses the inter-voxel correlations and identifies areas (in this case voxels) which have an independent contribution to the outcome measure. These associations are corrected for age, gender, education year and prior TIA or ischemic stroke. Significance of the clusters is shown in color ranging from yellow (−log10p=2, p = 0.01) to red (−log10p>3, p < 0.001). In order to visualize the voxels that were included in each step of the analyses, voxels that were associated with cognition in the univariate analyses, but not in the multivariate analyses, are shown in light blue (corresponding to the step referred to as ‘feature selection’ in the methods) and the remaining voxels are shown in dark blue. Uncolored voxels were not included in any step of the analyses because such lesions were found in <4 individuals. The slice showing the infratentorial regions varies across different domain to best visualize the significant clusters. The figures are shown in neurological convention (left is on the left).

Figure 3.

Results of multivariate region of interest-based analyses using support vector regression (SVR). The ROIs where the regional infarct volume was statistically associated with the cognitive functions are colored from yellow (−log10p = 2, p = 0.01) to red (−log10p > 3, p < 0.001). ROIs that were associated with cognition in the univariate analyses but not in the multivariate analyses are shown in light blue (corresponding to the step referred to as ‘feature selection’ in the methods). The names of the significant ROIs were attached above and the corresponding p-value and weight coefficient (beta) are shown in Table 2 for global cognition and Table 3 for cognitive domains. The figures are shown in neurological convention (left is on the left). ACR: anterior corona radiata; AIC: anterior limb of internal capsule; BCC: body of corpus callosum; Cing: cingulum (white matter); EC: external capsule; GCC: genu of corpus callosum; IFGop: inferior frontal gyrus (opercular); IFGorb: inferior frontal gyrus (orbital); IFGtri: inferior frontal gyrus (triangular); IFOF: inferior fronto-occipital fasciculus; MOL: middle occipital lobe; MTG: middle temporal gyrus; MTP: middle temporal pole; PCR: posterior corona radiata; PIC: posterior limb of internal capsule; PTR: posterior thalamic radiation; RIC: retrolenticular part of internal capsule; SCR: superior corona radiata; SFOF: superior fronto-occipital fasciculus; SLF: superior longitudinal fasciculus; SPG: superior parietal gyrus; STG: superior temporal gyrus.