Visual Deprivation Selectively Reshapes The Intrinsic Functional Architecture Of Anterior Insula Subregions

Purpose: The anterior insula(AI)is the core hub of the salience network that serves to identify the most relevant stimuli among the vast sensory inputs and forward them to higher cognitive regions to guide behaviours.As blind subjects were usually reported with changed perceptive abilities for salient non-visual stimuli,we hypothesized that the resting-state functional network of the AI is selectively reorganized after visual deprivation.Methods: A region of interest(ROI)-based functional connectivity(FC)analysis was performed in 20 congenitally blind(CB),27 early blind(EB),44 late blind(LB)subjects,and 50 sighted controls(SC).The bilateral dorsal general cognitive subregion and ventral social-emotional subregion in the AI[1] which serve as the core hub of the salience network were used as ROI seeds for the intrinsic functional connectivity calculation.In order to investigate the effect of onset age of blindness on the resting-state functional connectivity when considering the factors of hemosphere and subregion,a 4 group(CB,EB,LB,and SC)× 2 hemisphere(left and right)× 2 subregion(dorsal and ventral AI)mixed-model analysis of variance(ANOVA)were performed based on a general linear model(GLM)within a gray matter mask.We considered groups(CB,EB,LB and SC)as the between-subjects effect,and hemispheres(left versus right AI)and subregion(dorsal versus ventral AI)as the within-subjects effects.In the present study,we investigated the interaction effects between group and subregion,between group and hemispheres,and among the three factors.Multiple comparisons were corrected using a voxel-wise false discovery rate(FDR)methods(q < 0.01).If any significance existed in each of these interactions,a voxel-wise post hoc analysis was further performed to clarify the potential differences in FC between each pair of the 4 groups at each level of other factors(hemisphere or subregion)within the searching voxels that showed statistically significant interaction effects(q<0.01,FDR correction).Finally,voxel-wise regression analyses were carried out to investigate the association between the onset age of blindness and the FC of AI subregions(q<0.01,FDR correction).Results:1.The 4 groups(CB,EB,LB,and SC)× 2 hemispheres(left versus right side)× 2 AI locations(dorsal versus ventral area)mixed-model ANOVA revealed significant interactions between the groups(CB,EB,LB and SC)and AI locations(dorsal versus ventral area)with respect to the FC(q <0.01,FDR corrected),indicating diverse inter-group differential patterns in the resting-state FC between the dorsal and ventral AI.Brain regions demonstrating significant interactions were mainly located in the bilateral intraparietal area(IPA),calcarine sulcus(CalS)and lingual gyrus(LG),and the right middle occipital gyrus(MOG).2.One-way ANOVA and post-hoc inter-group comparisons of the FC of the dorsal AI are shown in Fig.2(q <0.01,FDR corrected).For the dorsal AI,there were significant inter-group FC differences between the dorsal AI and the bilateral IPA,CalS and LG,and the right MOG.Post hoc analyses revealed that the CB had a higher dorsal AI FC with the bilateral IPA and CalS,while a lower FC with the left LG and the right MOG than the SC;the EB and LB had higher dorsal AI FC with the IPA,while lower FC with the bilateral LG than the SC.In comparisons within the blindness groups,the CB had higher dorsal AI FC with the bilateral CalS and the right IPA,while lower FC with the left LG and the right MOG than the EB and LB;the EB showed a higher dorsal AI FC with the right MOG,and a lower FC with the bilateral LG than the LB.3.One-way ANOVA and post-hoc inter-group comparison of the FC of the ventral AI are shown in Fig.3(q < 0.01,FDR corrected).For the ventral AI,there were significant inter-group FC differences in the bilateral CalS and LG.Post hoc analyses further revealed that all the blind groups had a higher ventral AI FC with the bilateral LG and CalS compared with the SC.In comparisons within the blindness group,both the CB and EB showed higher FC with the right CalS and the bilateral LG than the LB,while there were no significant differences in the FC between the CB and the EB.4.Voxel-wise regression analyses revealed significant negative associations in FC between the dorsal AI and the right IPA,and between the ventral AI and the right LG(q <0.01,FDR corrected)with the onset age of blindness.Conclusion:1.The intrinsic functional networks of AI subregions were selectively reshaped afer blindness,exhibiting a strengthened FC of the dorsal AI with the dorsal visual stream,and a strengthened FC of the ventral AI with the ventral visual stream.These fndings suggest two parallel dorsal and ventral pathways that selectively transfer non-visual salient general congnitive and social emotional information between the deprived “visual” cortex and salience network for blind individuals to reserve comparable adaptive cognition,emotion and behavior toward the non-visual world.2.Different reorganization pattern of the intrinsic functional network of AI subregions toward the dorsal visual stream was found in the blind groups.The functional connectivities of the dorsal AI were strengthened with the dorsal visual stream in the blind,while weakened with the ventral visual stream;in contrast,the functional connectivity of the ventral AI was strengthened with the ventral visual stream in the blind while no significant functional connectivities reorganization with the dorsal visual stream.The inverse changes of FC of the dorsal and ventral stream with the dorsal AI might indicate a deficiency of blind subjects in integrating the spatial and object information for cognitive processing.3.These common fndings including the consistent higher dorsal AI FC with the bilateral IPA among all the blind groups,the consistent higher ventral AI FC with the bilateral LG and CalS among all the blind groups compared with the SC,the minimal inter-subgroup difference in FC between AI and these core regions,and the partially negative associations in FC between the dorsal AI and the right IPA,and between the ventral AI and the right LG with the onset age of blindness indicates that the reorganization of the intrinsic functional architecture of AI of blind subjects was mainly driven by combined influences by experience-dependent and degenerative factors,and that the onset of age of blindness also exerts minor effects on this process.