Motor recovery and microstructural change in rubro-spinal tract in subcortical stroke

Abstract

The mechanism of motor recovery after stroke may involve reorganization of the surviving networks. However, details of adaptive changes in structural connectivity are not well understood. Here, we show long-term changes in white matter microstructure that relate to motor recovery in stroke patients. We studied ten subcortical ischemic stroke patients who showed motor hemiparesis at the initial clinical examination and an infarcted lesion centered in the posterior limb of internal capsule of the unilateral hemisphere at the initial diffusion-weighted magnetic resonance imaging scan. The participants underwent serial diffusion tensor imaging and motor function assessments at three consecutive time points; within 2 weeks, and at 1 and 3 months after the onset. Fractional anisotropy (FA) was analyzed for regional differences between hemispheres and time points, as well as for correlation with motor recovery using a tract-based spatial statistics analysis. The results showed significantly increased FA in the red nucleus and dorsal pons in the ipsi-lesional side at 3 months, and significantly decreased FA in the ipsi-lesional internal capsule at all time points, and in the cerebral peduncle, corona radiata, and corpus callosum at 3 months. In the correlation analysis, FA values of clusters in the red nucleus, dorsal pons, midbody of corpus callosum, and cingulum were positively correlated with recovery of motor function. Our study suggests that changes in white matter microstructure in alternative descending motor tracts including the rubro-spinal pathway, and interhemispheric callosal connections may play a key role in compensating for motor impairment after subcortical stroke.

Keywords: CC, Corpus callosum; CP, Cerebral peduncle; CR, Corona radiata; DTI, Diffusion tensor imaging; Diffusion tensor image; EPT, Extrapyramidal tract; FA, Fractional Anisotropy; FMMS, Fugl-Meyer Motor Scale; Motor recovery; PLIC, Posterior limb of internal capsule; PT, Pyramidal tract; Reorganization; Subcortical stroke; TBSS, Tract-based spatial statistics; Tract-based spatial statistics.

Fig. S1

Infarcted area shown in the acute-stage diffusion weighted images of each patient from #1 to #10. Yellow arrow indicates high intensity area which suggests ischemic lesion.

Fig. 1

Lesion overlap of the stroke patients in the current study. The lesion mask of each patient (drawn on the isotropic DWI image at Scan 1 in the native space) was warped to and overlaid on a standard MNI brain space. The number of lesions overlapped is color coded in the range of pink (n = 1) to white (n = 7).

Fig. 2

Inter-hemispheric effect on FA images in TBSS. A) Inter-hemispheric FA difference between ipsi- and contra-lesional hemispheres in each scan session of Scans 1, 2, and 3. In Scans 1 and 2, significantly decreased FA (corrected p < 0.05, color coded in blue-green) was located mainly in the posterior limb of internal capsule (PLIC) and within a frequently infarcted region (as color coded in pink-white), whereas in Scan 3, the region of decreased FA extended distally (cerebral peduncle, white arrow head), and proximally (corona radiata, blue arrow head), and into anterior and posterior parts of the corpus callosum (yellow arrow head). B) Inter-hemispheric FA differences at Scan 3. Note that increased FA (corrected p < 0.05, color coded in red-yellow) was found in the dorsal pons (labeled as c5) and red nucleus (c6). Other clusters with decreased FA are labeled by: c1, cerebral peduncle (CP) through pyramidal tract (PT) of the pons; c2, PLIC through corona radiata (CR); c3, rostral parts and genu of corpus callosum (CC) and c4, isthmus of CC. Frequency of infarcted lesion is color coded by pink (n = 1) to white (n = 7). For visualization purposes, clusters were enhanced by spherical smoothing with a 1.5-mm radius. See also Table 2 for lists of clusters..

Fig. 3

Inter-hemispheric and time-dependent changes in FA in regions of interest (ROIs). Plots of FA values in clusters (c1–c6, see also Fig. 2B) and contralateral mirror regions against scan sessions (Scans 1, 2, and 3). Significant effect of scan session was found in clusters c1, c2, c3, c5 and c6 (F-values shown in each graph), but not in other clusters including mirror regions. *p < 0.05, **p < 0.01 with post-hoc Tukey's test between sessions; † p < 0.05, ‡ p < 0.05 with paired t-test between the cluster and corresponding mirror region.

Fig. 4

Correlation of serial FA images with scores of motor function. A) Clusters with positive correlation between FA and FMMS scores (uncorrected p < 0.05, color coded in red-yellow) were found in midbody of CC (c7) and cingulum (c8). See also Table 3 for lists of clusters. B) Plots of FA values against FMMS scores in clusters c5, c6 (see also Fig. 2B), c7 and c8. † p < 0.05, ‡ p < 0.01 with Pearson's correlation analysis.