| Background and Purpose:Early studies have indicated that the cortico-rubro-spinal tracts play important roles in motor dysfunction after stroke.In this study,we studied the differential involvement of the rubral branches in capsular and pontine stroke,and their associations with the motor impairment.Subjects and methods:The rubral branches,including bilateral corticorubral tracts(CRT),dentatorubral tracts(DRT),and rubrospinal tracts(RST),and the cortico-spinal tract(CST)were reconstructed based on the dataset of diffusion spectrum imaging(DSI)of 100 subjects from the Human Connectome Project.After that,we constructed the probability map of the above fiber bundles at group level.In the present study,93 cases with capsular stroke(CS),38 cases with pontine stroke(PS)and 87 age-and sex-matched normal control(NC)subjects were recruited.The infarct volume of stroke patients was measured.All patients underwent Fugl-Meyer assessment(FMA)which is frequently used to evaluate the motor impairment in clinical practice.The pre-processed DSI data of all subjects were used to extract the diffusion indices including fractional anisotropy(FA),axial diffusivity(AD),and radial diffusivity(RD).According to the side of the lesions,all the stroke patients were divided into left-and right-side lesion group.Voxel-based analysis(VBA)was performed for each fiber bundle.The differences of CRT,RST,DRT and CST FA values among the CS,PS and NC were compared by one-way analysis of covariance(ANCOVA).The mean FA,AD and RD of clusters with significant differences in each tract were extracted,and ROI-wise post hoc tests were carried out using the GLM model in the PASW statistics 19 software to compare group differences in these diffusion scalars between each pair of groups.The false discovery rate(FDR)method was used to correct for multiple comparisons(q<0.05).Partial correlation analysis(controlling for the effects of age,gender,and scanners)was used to test the relationship between the integrity of each red nucleus fiber bundle and CST microstructure and the impairment of motor function.To further elucidate whether the integrity of the rubral branches contributes independently to the residual motor impairment that is irrespective of the CST,the FA values of ipsilesional CST was used as an additional covariate to calculate whether the correlations between the FA values of each rubral branch and the FMA scores were significant(q<0.05,FDR correction).In order to evaluate the predictive power of the integrity of the rubral bundle branches for the individual variance in severity of motor impairment,we applied a multiple regression model with the total FMA score as the dependent variable,and the FA value of the bilateral DRT and RST,and that of ipsilesional CRT as the independent variables(features).Before model estimation,the effects of age,gender,and scanners were regressed out from each feature.An F-test was used to evaluate the statistical significance(q<0.05,FDR corrected),and adjusted R-square value was used to evaluate the predictive power of the model.Results:VBA analyses identified significant differences in FA of ipsilesional rubral branches in patients with left and right stroke lesions(P<0.05,cluster-wise FWE correction).ROI-wise post hoc analyses demonstrated significantly lower FA in the ipsilesional CRT in the CS than that in the NC.The lower FA was found in the contralesional CRT in the left CS than in the NC.The ipsilesional and contralesional DRT in the PS had significantly lower FA than those in the NC.The ipsilesional and contralesional RST in both CS and PS on both sides had significantly lower FA than those in the NC.The ipsilesional CST had significantly lower FA than that in the NC(P<0.05,FDR correction).Partial correlation analyses identified significantly positive correlations between the FA of ipsilesional CRT and the FMA total and upper extremity scores in the CS,between the FA of bilateral RST and the FMA scores in both the CS and PS,as well as between the FA of contralesional DRT and FMA total,upper and lower extremity scores in the PS(q<0.05,FDR correction).We still found significantly positive correlations between the FA of both ipsilesional and contralesional RST and FMA lower extremity scores in the PS when the FA of ipsilesional CST were additionally regressed out from the partial correlation model(q<0.05,FDR correction).Multiple linear regression model analysis revealed that the composite FA predictive power of all the involved rubral branches could explain 39.2%(R~2)of the variance in FMA scores in CS patients(F=6.023,P<0.001),and the R2 was 48.8% in PS patients(F=4.817,P=0.008).Conclusion:In the patients with capsular stroke,lesions could mainly lead to direct damage to the ipsilesional CRT and indirect damage to the ipsilesional and contralesional RST.The bilateral rubral branches are heterogeneously affected by capsular stroke lesions: the bilateral DRT are damaged in patients with right capsular lesion,but not in patients with left capsular lesion.Moreover,the contralesional CRT is impaired by the lesions in the left capsular region,but not by the lesions in the right capsular region.Although PS patients showed direct and indirect damage in the bilateral RST and DRT,the relatively intact CRT may be related to the larger distance from stroke lesions,and/or the trans-synaptic axonal degeneration is much slower in the central nervous system of humans.The integrity of CRT and RST is related to the severity of motor impairment,and the correlation between the integrity of RST and the severity of lower limb motor impairment still exists after removing the influence of ipsilesional CST injury on motor function,indicating that RST may affect lower limb motor function independently.Multiple linear regression analysis showed that after eliminating the influence of CST injury on motor function,the FA values of rubral bundles can predict the degree of motor impairment in CS and PS patients,suggesting that the integrity of rubral bundles could independently affect the motor function in these patients. |
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