Multimodal Imaging Study Of Brain Structural And Functional Reorganization After Visual Deprivation

Part1:The effect of visual deprivation at different developmental stages on the reorganization of brain structure[Purpose] In this study, we used multiple structural analysis methods, including cortical thickness, gray matter volume (GMV) and diffusion indices analysis, to elucidate the following issues:(1) the effect of critical developmental period on the brain structural reorganization;(2) the association between these structural indices and the onset age of blindness.[Methods] Twenty congenitally blind (CB),31early blind (EB),53late blind (LB), and40sighted control (SC) subjects were recruited in this study. Three-dimensional T1weighted imaging and diffusion tensor imaging (DTI) were acquired using3.0T MRI scanner. We constructed the whole brain cortical thickness and gray matter volume using the3D T1data, and obtained the diffusion fractional anisotropy (FA) based the DTI data. Voxel-based and ROI-based analyses were used to test the group differences in the above-mentioned structural indices. We also investigated the association between these indices and the onset age of blindness using partial correlation coefficient.[Results](1) Compared with the SC, the CB showed significantly thickened cortex in the early and ventral visual areas, and thinned cortex in the temporal pole, fusiform, and precentral gyrus; in contrast, the LB manifested decreased thickness in the ventral visual areas and the MT+. The EB only showed thinned cortex in the MT+. Negative correlation between the onset age of blindness and cortical thickness was found in the early and ventral visual areas.(2) All the blind subgroups showed decreased GMV in the visual cortex, and increased GMV in the paracentral gyrus; moreover, the early visual areas were more involved than the higher ones, and the LB were more involved than the CB. Negative correlation was shown between the GMV and onset age of blindness in the early and ventral visual areas.(3) Each blind subgroup showed reduced FA in the anterior visual pathway, and the LB and EB showed more broadly distributed than the CB. However, there were no significant differences in the FA among each pair of the three blind subgroups, and no statistical correlation was shown between the FA and onset age of blindness.[Summary](1) Early visual experience plays critical roles in the structural reorganization of the visual and other sensory cortices after visual deprivation.(2) Onset age of blindness also significantly influences the reorganization of the visual cortex, and the effect even continues after the critical developmental period.Part2:Functional connectivity plasticity in congenitally and late blind subjects[Purpose] This study introduce the functional connectivity density (FCD) to test two hypotheses:(1) CB and LB subjects exhibit similar functional dis-connectivity because they are subjected to similar damage in the retinofugal pathway;(2) CB subjects will exhibit more extensive increase in FCD than LB subjects will, because brain owns strong capacity for cross-modal plasticity during the critical period of development.[Methods] Nineteen CB,34LB and43SC were performed resting-state functional MRI. After routing preprocessing steps, the whole brain short-range and long-rang FCD were calculated. Voxel-wise comparison of the FCD among the three groups, correlation between the FCD and onset age of the blindness was performed.[Results] Compared with the SC, the CB showed decreased short-and long-range FCD in the early visual cortex, and increased FCD along the ventral and dorsal stream. The LB showed more broadly decreased FCD in the early visual cortex, and even in the posterior thalamus. They also display significantly increase FCD along the ventral and dorsal stream, but showed weaker involvement in the ventral one compared with the CB. Finally, the short-range FCD at the left primary visual cortex was negatively correlated with the onset age of blindness. [Summary] Visual deprivation both at the early and late stage can significantly reshape the resting-state functional organization. Furthermore, visual experience plays an important role in reshaping the functional connectivity in the ventral visual pathway.Part3:The development of visual areas depends differently on visual experience[Purpose] As discussed in the former sections, remarkable structural and functional reorganization of visual cortex was found in the CB, however, little is known the changes in each visual area. This study used cortical thickness analysis and FC analysis to verify the following hypothesis:(1) the development of visual areas depends differently on visual experience;(2) the FC between the higher-tier and early visual areas will develop normally in CB subject.[Methods] Thirteen CB and56SC were involved in this study, and3D T1WI and rs-fMRI were acquired. The cortical thickness was extracted. The FC between S1and the visual cortex, and those between each pair of visual areas were calculated.[Results] The thickness of early visual areas showed significantly increase in the CB, while many higher tier areas showed no differences with the SC. The FC between visual cortex and the S1were significantly decreased in the CB; furthermore, the early areas showed more involvement than the higher one, and the ventral areas were more involved than the dorsal one. The FC within visual areas in the same hemisphere were normal or strengthened, while those in different hemisphere were weakened.[Summary] The development of visual areas depends differently on visual experience, which can explain most findings about the structural and functional reorganization in the visual cortex in the CB. The strengthened FC within the ipsilateral visual areas suggests the indirect cortico-cortical connection is a candidate pathway that non-visual signals reach the V1. Part4:Enhanced spontaneous functional interactions in attention networks in congenitally blind individuals[Purpose] Many studies showed the CB has superior tactile/auditory perceptive performance than the SC, and attention may plays role in the neural process. This study using FC analysis to verify the following hypothesis:(1) the FC within the attention network were strengthened in the CB;(2) the FC between attention network and occipital cortex were also strengthened. Clarifying the above issues can explain the neural mechanism of the non-visual processing in the occipital cortex.[Methods] This study involved39CB and76SC. The rs-fMRI and DTI data were used for analysis. We first extract the dorsal attention network (DAN) and ventral attention network (VAN). Group differences of the FC within the attention network and between attention network and the occipital cortex were analyzed. Finally, probabilistic tractography was carried out to find the anatomical connections between attention network and the occipital cortex.[Results] Compared with the SC, we only found strengthened FC within the DAN, and between DAN and the other attention network. Furthermore, the FC between fronto-insular attention nodes and the occipital cortex were strengthened. Finally, the structural connections were shown between fronto-insular attention nodes and the occipital cortex.[Summary](1) The strengthened FC within the attention network contributed to the improved tactile/auditory performance in the CB.(2) The cross-modal activation of occipital cortex may be caused by strengthened FC between fronto-insular nodes and occipital cortex.(3) Fronto-insular-occipital is a candidate pathway that endogenous attention signals reach the occipital cortex.Part5:Altered white matter integrity in well-recovered chronic stroke patients [Purpose] The former studies demonstrated that multimodal imaging analysis is robust to reveal the structural and functional reorganization in the blind. To clarify that these methods can also be powerfully utilized in other brain injury model, we recruited a group of sub-cortical stroke patients with well-recovered motor function. DTI analyses were used to elucidate the following issues:(1) Do these patients undergo persistent damage in the motor-related fibers that seem not to affect the major motor function;(2) whether can white matter integrity changes predict the fine motor deficit.[Methods] This study selected28chronic stroke patients with well-recovered motor function. The neurological examinations were measured, including the Fugl-Meyer score, grip force test (GFT), nine hole peg test (NHPT) and MMSE. DTI images were acquired and the diffusion indices were extracted from the DTI data. Multiple analysis methods including the TBSS, VBA and ROI-wise analysis were introduced to evaluate the changes of the diffusion indices in the whole brain white matter. The correlations between diffusion indices and fine motor score (GFT and NHPT) were also test.[Results] This study did not find any reduce in FA at the ipsilesional CST, nor increase in any brain area. Significantly decreased FA was shown in bilateral peri-dentate tract, ipsilesional brachium pontis, and ipsilesional posterior thalamus. Further analysis showed decreased FA is mainly caused by increased transverse eigenvalue. Finally, the FA of peri-dentate tract showed significant correlation with the fine motor scores.[Summary](1) Even in chronic stroke patients with well-recovered global motor function, the cerebellar white matter still suffers persistent secondary damages.(2) Diffusion properties of the peri-dentate fibers may be considered as a potential biomarker in predicting the prognosis of fine motor function.ConclusionsUsing multi-modal imaging techniques and comprehensive data analysis methods, we investigated the brain structural and functional reorganization after visual deprivation. Our result demonstrated:first, early visual experience plays critical role in both the structural and resting-state functional reorganization of brain. Second, onset age of blindness also affects the reorganization pattern of visual cortex. Third, the development of visual areas depends differently on visual experience. Fourth, In the CB, functional interactions within the attention networks and those between attention networks and occipital cortex are strengthened. Finally, we proposed that the non-visual signals could reach the visual cortex via the parietal-occipital indirect cortico-cortical pathway, or the fronto-insular-occipital direct cortico-cortical pathway.