Degeneration of corpus callosum and recovery of motor function after stroke: a multimodal magnetic resonance imaging study

Abstract

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke-affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke.

Figure 1

Lesion map. The lesion mask of each patient (drawn on the respective T1‐weighted images) was spatially normalized to and overlaid on a Montreal Neurological Institute (MNI) brain template. The color code indicates the degree of overlap across patients.

Figure 2

Brain activity pattern during index finger movements of the right/paretic hand with maximum speed. Compared with controls, stroke patients showed abnormally enhanced activity in bilateral motor areas (A) and reduced laterality indices (B) when moving the affected hand. Aff‐H, affected hemisphere. See also Supporting Information Table II for individual fMRI laterality indices.

Figure 3

Voxelwise correlation analyses between FA and fMRI laterality index as well as ARAT scores in patients (n = 18). FA values positively correlated with both the laterality index during movements of the affected index finger (A) and ARAT scores (B) (p < 0.05, FWE corrected at the cluster level). Shown are clusters in: 1 and 2, body of corpus callosum; 3, internal capsule; 4, posterior limb of internal capsule and adjacent inferior longitudinal fasciculus and fronto‐occipital fasciculus; 5, body of corpus callosum; 6, internal capsule; 7, cortico‐pontine‐cerebellar tract; 8, superior longitudinal fasciculus; 9, genu of corpus callosum; 10, splenium of corpus callosum. Parts of cluster 3, 4, and 6 are within the lesion zone (Supporting Information Fig. 1). For visualization, clusters were “thickened” by applying spherical smoothing with 2 mm radius. Aff‐H: Affected hemisphere.

Figure 4

Region of interest analyses: Partial correlation between fMRI laterality index and parallel diffusivity as well as perpendicular diffusivity. The parallel diffusivities (except for cluster 3) were positively correlated with the laterality index controlled for perpendicular diffusivity, age of patients, and lesion age (A), but the perpendicular diffusivities were negatively correlated with the laterality index controlled for parallel diffusivity, age of patients, and lesion age (B). The locations of the four clusters are shown in Figure 3A. Variables: 1, laterality index; 2, parallel diffusivity; 3, perpendicular diffusivity; 4, age of patients; 5, lesion age. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 5

Region of interest analyses: Partial correlation between ARAT scores and parallel diffusivity as well as perpendicular diffusivity. The parallel diffusivities in the regions shown in Fig. 3B were positively correlated with ARAT scores controlled for perpendicular diffusivity, age of patients, and lesion age (A), but the perpendicular diffusivities were negatively correlated with ARAT scores controlled for perpendicular diffusivity, age of patients, and lesion age (B). Variables: 1, ARAT scores; 2, parallel diffusivity; 3, perpendicular diffusivity; 4, age of patients; 5, lesion age. **p < 0.01, ***p < 0.001.

Figure 6

Probabilistic fiber tracking with seeds in the corpus callosum (thresholded at more than eight subjects). The area covered by cluster 1 (seed region, shown in Fig. 3A) in the corpus callosum connected to the medial and ventral side of the precentral gyrus as well as the postcentral gyrus (corresponding to M1, SMA, vPMC, and primary somatosensory cortex; A). Cluster 2 (seed region, shown in Fig. 3A) in the corpus callosum connected to the medial side of both superior parietal lobules, temporal cortices, and precentral gyri (corresponding to M1) (B). The green area indicates the lesion volume of the sample of patients in this study. The stroke lesions affected the white matter fibers connecting to bilateral SMA and vPMC (C). The posterior part of the lesions also affected the fibers connecting to the parietal lobules bilaterally (D). Aff‐H, affected hemisphere. The green line in the figure indicates the central sulcus. The color bar indicates the number of superimposed tract masks of the patients (red/blue: representations in nine patients; yellow/light blue: representations in 18 patients).