An MRI Study On Brain Structural And Functional Alterations After Treatment In Children With Anisometropic Amblyopia

Objective This study aims to investigate changes in the brain structural and functional indexes after treatment in children with anisometropic amblyopia（AA）by using structural and functional magnetic resonance imaging techniques,and to analyze their correlation between significantly different brain structural and functional indexes and with clinical variables in ophthalmology,including best-corrected visual acuity examination,stereo examination,optical coherence tomography,and pattern visual evoked potential examination.The study provides objective imaging evidence for the neural rehabilitation mechanism of children with AA.Methods This study was conducted on 25 children with AA who were treated at the ophthalmology department of the Gansu Province Hospital Rehabilitation Center.All subjects underwent ophthalmological exams and cranial magnetic resonance imaging,in the baseline period and one month after treatment.The ophthalmological exams included atropine maximal dilation refraction,best-corrected visual acuity examination,stereo examination,optical coherence tomography,and pattern visual evoked potential examination.The cranial magnetic resonance imaging included 3D-T1WI structural images scan,diffusion tensor images scan,and resting-state functional magnetic resonance imaging scan.Surface?based morphometry analysis of the 3D-T1WI structural images was performed to obtain four structural parameters,including cortical thickness,sulcus depth,gyrification index,and fractal dimension,to analyze the intergroup differences in structural indexes after treatment,to explore changes in brain structure in children with AA after treatment.Data processing and analysis of diffusion tensor images were performed to obtain four indexes,including fractional anisotropy,mean diffusivity,axial diffusivity,and radial diffusivity,to analyze the intergroup differences in white matter microstructure diffusion indexes after treatment,to investigate changes in brain white matter microstructure in children with AA after treatment.The resting-state functional MRI data were analyzed,and the amplitude of low-frequency fluctuation,the fractional amplitude of low-frequency fluctuation,and regional homogeneity were calculated.Meanwhile,using differences in brain regions obtained through structural MRI and resting-state functional MRI as seed points to conduct whole-brain functional connectivity analysis and compare the differences between groups.Finally,extracting the brain structural and functional indexes with significant differences after treatment.To analyze the correlation between these indexes and the ophthalmic clinical variables.Results Compared with the baseline period,the best-corrected visual acuity increased,the latency of pattern visual evoked potential shortened,the amplitude of pattern visual evoked potential increased,the thickness of the retinal nerve fiber layer decreased,the retinal thickness in macular decreased,and the stereo acuity decreased in children with AA after treatment,and the difference was statistically significant（P<0.05）.After treatment,the brain morphological indexes of AA children changed as follows:there was an increase in the cortical thickness of the left precentral gyrus and left inferior parietal lobule in children with AA.There was also an increase in the sulcus depth of the left superior frontal gyrus and left posterior cingulate gyrus.There was an increase in the gyrification index of the right cingulate gyrus,right precuneus,right precentral gyrus,left lateral occipital gyrus,left fusiform gyrus,left inferior frontal gyrus,and left middle frontal gyrus in children with AA after treatment.In addition,there was an increase in the fractal dimension of the right inferior parietal lobule and right middle temporal gyrus,and a decrease in the fractal dimension of the right middle temporal gyrus in children with AA after treatment（P<0.001）.There were no significant differences in all diffusion indexes of white matter microstructure after treatment（P>0.05,family wise error corrected）.After treatment,the resting state functional indexes changed as follows:the fractional amplitude of low-frequency fluctuation values of the left calcarine cortex and left middle temporal gyrus increased,while the fractional amplitude of low-frequency fluctuation values of the right posterior lobe of the cerebellum decreased after treatment in children with AA（P<0.05,Gaussian random field multiple comparison corrected）.There were no significant differences in the amplitude of low-frequency fluctuation and regional homogeneity values in children with AA after treatment（P>0.05,Gaussian random field multiple comparison corrected）.In terms of functional connectivity,there was a decrease in functional connectivity between the left lateral occipital gyrus and right cuneus and an increase in functional connectivity between the left lateral occipital gyrus and left lingual gyrus after treatment.There was also an increase in functional connectivity inside the left calcarine cortex,and a decrease in functional connectivity between the right posterior lobe of the cerebellum and the middle cingulate gyrus after treatment（P<0.05,Gaussian random field multiple comparison corrected）.The results of the correlation analysis showed a positive correlation between the increase in P₁₀₀ wave amplitude and the increase in gyrification index of the right precuneus（r=0.402,P=0.047）.With regards to best-corrected visual acuity,there was a positive correlation with the increase in the gyrification index of the left middle frontal gyrus and the right isthmus cingulate gyrus and the sulcus depth of the left posterior cingulate gyrus（r=0.448,P=0.025;r=0.422,P=0.036;r=0.543,P=0.005）.Shortening of the P₁₀₀ wave latency and thinning of the macular retina were found to be positively correlated with the increase in the sulcus depth of the left superior frontal gyrus（r=0.484,P=0.014;r=0.426,P=0.038）.The increase in P₁₀₀ wave amplitude was positively correlated with the decrease in functional connectivity between the left lateral occipital gyrus and right cuneus（r=0.440,P=0.028）,while the decrease in retinal nerve fiber layer thickness was positively correlated with the increase in functional connectivity between the left lateral occipital gyrus and left lingual gyrus（r=0.461,P=0.020）.However,there was no other significant correlation between the brain areas whose structural and functional indexes showed significant changes and clinical variables.Conclusion Compared to the baseline period,the visual function of AA children was significantly improved after treatment.At the same time,the morphological structure of gray matter and spontaneous brain activity and functional connectivity of brain regions related to vision changed,while the white matter microstructure did not show significant changes.It is suggested that the changes in cortical morphological structure and resting brain function in visual-related brain regions may be involved in the neural pathological basis of amblyopia rehabilitation.This study provides a new perspective for further understanding the neural rehabilitation mechanisms in AA children.