| Backgrounds and objective:More and more evidence have predicated that amputation or deafferentation of a limb induces functional or structural recognization in sensory and motor cortices.However,the extent of structural reorganization after lower limb amputation remains uncertain.Therefore we combine grey matter(GM)and white matter(WM)to investigate the plasticity of the brain following lower limb amputation.At the same time,as the amputation could cause the change of the movement,we focus on the brain changes in the visual-moving area.Although few studies have reported that amputees presented gray matter changes in the visual areas,it is still unclear which subregions are specifically involved.We hypothesized that amputation at the lower limb can result in neural changes in the specific visual areas that are measurable with brain imaging.In order to systematically characterize the brain reorganization,the mean cortical thickness in each of the visual areas was measured using surface-based morphology and regions of interest(ROI)approach.In addition,the relationships between imaging measures and clinical variables were also investigated.Materials and Methods:1.The plasticity of brain gray matter and white matter following lower limb amputationIn this investigation,17 adult patients with right lower limb amputation and 18 healthy control subjects were studied using T1-weighted magnetic resonance imaging(MRI)and diffusion tensor imaging(DTI).We investigated cortical thickness and fractional anisotropy(FA)of white matter(WM)as proxies of brain reorganization in each tissue.All the structural T1 images were analyzed using FreeSurfer to create anatomical surface models.Group differences in age,years of education,and neuropsychological scores were examined using independent samples-tests.Sex data were analyzed with a chi-square test.Differences in FA between the amputees and controls were determined using the FSL “randomize” tool,which is specifically designed for permutation testing with nonparametric values.Age and sex were used as the covariates.Regional differences between amputees and controls were assessed using a vertexby-vertex general linear model controlling for the potential confounding effects of age,sex,and TIV.Analyses of Covariance(ANCOVA)adjusting for age and sex were used to explore the group differences in the mean FA value for each of the fiber tracts generated by PDT and in the mean cortical thickness for each of the selected sensorimotor regions in both hemispheres.Finally,the relationships between the WM and GM changes were investigated using partial correlation analyses(adjusted for age and sex).A false discovery rate(FDR)corrected threshold of 0.05 was considered as significant for these analyses.2.Progressive thinning of visual motion area in lower limb amputeesIn this investigation,48 adult patients with unilateral lower limb amputation and 48 healthy control subjects(sex-and age-matched)were studied using T1-weighted magnetic resonance imaging scanned by a 3.0T MRI.Continuous variables were tested for normality using the Shapiro–Wilk test.Differences in the demographic measurements were assessed using two sample t-tests,and the chi-square test was used for gender.Cortical thickness was calculated as the average of the distance from the white matter surface to the closest point on the pial surface and from that point back to the closest point on the white matter surface.For each visual area,we computed the average cortical thickness across the unilateral area,as the indicator of brain change.Multiple Analyses of Covariance(MANCOVAs)were conducted to examine the differences of the cortical thickness measurements between amputees and normal controls,using age and gender as covariates.Furthermore,mixed-model multivariate analysis of variance(MANOVA)designs with amputation side(left vs.right)and amputation site(femur vs.tibia)as between-group factors,age and gender as covariates,and the different subregions of the visual cortex as repeated measures were used to investigate the effects of confounding variables on the imaging measurements in amputees.Results:1.The plasticity of brain gray matter and white matter following lower limb amputationIn amputees,a thinning trend was shown in different cortical areas,with the largest one in the left premotor cortex(PMC).Some smaller clusters were also noted in the bilateral occipital lobes,right temporo-occipital junction,precentral gyrus,precuneous lobe,left inferior parietal lobule and orbitofrontal cortex.In addition,the amputees exhibited a decreased FA value in the right superior corona radiata and WM regions underlying the left PMC as compared with controls.Furthermore,compatible with the hypothesis that amputation can lead to the change of the interhemispheric interactions,fiber tractography from these WM regions showed microstructural changes in the commissural fibers connecting the bilateral premotor cortices.Finally,the lower limb amputees also display significant FA reduction in the right inferior frontooccipital fasciculus(IFOF),and this reduction is negatively correlated with the time span after amputation.2.Progressive thinning of visual motion area in lower limb amputeesCompared with the normal controls,the amputees exhibited significantly lower thickness in the Middle Temporal Complex(V5/MT+)visual area.The V3 d also exhibited a thinning trend(p = 0.055).There was no significant difference in the other visual areas between the two groups.In addition,no significant difference of cortical thickness was found between patients with amputations at different levels.Across all the amputees,correlation analyses revealed that the cortical thickness of the V5/MT+ was negatively correlated to the time since amputation(? =-0.37,p = 0.01).Conclusion:1.The plasticity of brain gray matter and white matter following lower limb amputationIn this study,we combined high-resolution brain structural MRI and DTI to investigate the existence and extent of cortical and WM plasticity in subjects with right lower limb amputation.In summary,we found specific motor and somatosensory plastic changes in amputees without PLP and provided an update on the plasticity of the human brain involving both GM and underlying WM after limb injury.2.Progressive thinning of visual motion area in lower limb amputeesIn this study,high-resolution brain structural MRI was used to investigate the existence and extent of cortical reorganization in subjects with lower limb amputation.We focused on the visual cortex regions and found that amputation of unilateral lower limb may be associated with reduced cortical thickness in the V5/MT+ area.Moreover,we found negative correlation between the time since amputation and cortical thickness of the V5/MT+,indicating that the atrophy of V5/MT+ cortex was progressive.This might be attributed to the degeneration of biological motion perception or tactile motion processing.Though our findings are preliminary and need to be confirmed by future studies,they provide an initial insight into the nature of human adult brain reorganization within cortical cortex after limb injury. |
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