Functional And Structural Brain Alterations In Children And Adults With Anisometropic Amblyopia: A Comparative MRI Study

Backgrounds and objective:Amblyopia is a neurodevelopmental disorder of the visual system which is caused by the abnormal visual experience during the critical period of visual development and characterized by spatial vision deficiency.Amblyopia is the most common cause of visual impairment in children and often persists into adulthood.Anisometropic amblyopia is the most common type in both amblyopic children and adults.In clinic,it is generally believed that amblyopia can be effectively treated in young children,but is almost irreversible in adults.This phenomenon reveals neural system variations between children and adults with amblyopia,but the exact neural basis is still not fully understood.The neural basis of amblyopia has been a matter of interest for many decades,but the exact neural mechanisms are not completely understood.Although many studies have found the abnormal neuronal responses and extensive visual processing deficits both within and beyond V1,just few studies focus on the neurophysiologic abnormalities from the integration of functional and structural brain alterations.Moreover,there is still little knowledge about the differences of functional and structural brain alterations between children and adults with amblyopia.With the development of magnetic resonance imaging(MRI)in recent years,both the structural MRI and functional MRI are widely and successfully used in brain studies.In addition,these single-modal MRI techniques can be combined as a multi-modal MRI technique,which provides us a powerful tool to investigate the loci and extent of functional and structural brain alterations in amblyopia.To better understand the neural mechanisms underlying amblyopic children and adults,we used the multi-modal MRI technique to explore the functional and structural brain alterations both in children and adults with anisometropic amblyopia in the present study.We compared not only the differences between amblyopic patients and the normal-sighted controls,but also the differences between amblyopic children and adults.Furthermore,we expected that functional and structural brain alterations would be clinically relevant,so that the relationships between the functional/structural parameters and clinical variables were also analyzed.Material and methods:The present study contains the following four parts:1.Task-based f MRI: Nineteen monocular anisometropic amblyopia(9 children and 10 adults)and 20 normal-sight controls(8 children and 12 adults)were enrolled and divided into child group and adult group in this part.Task-based f MRI combined with visual stimulus for different visual pathway was performed in all participants and analysis of blood oxygenation level dependent(BOLD)signal in primary visual cortex(V1)was conducted in each participant.The relationship between the altered BOLD signal and clinical variables was also analyzed.2.Resting-state fMRI: Forty monocular anisometropic amblyopia(20 children and 20 adults)and 40 normal-sight controls(20 children and 20 adults)were enrolled and divided into child group and adult group in this part.Resting-state f MRI was performed in all participants and analysis of amplitude of low frequency fluctuation(ALFF)within the whole brain was conducted in each participant.ALFF value differences between the patients and controls in the two groups were compared.The relationship between the altered ALFF value and clinical variables was also analyzed.3.Structural MRI for Gray Matter: The participants were same as the part 2.Three-dimensional high resolution structural MRI was performed in all participants and analysis of cortical thickness within the whole brain was conducted in each participant.The relationship between the altered cortical thickness and clinical variables was also analyzed.4.Structural MRI for White Matter: The participants were same as the part 2.Diffusion tensor imaging(DTI)combined with tract-based spatial statistics(TBSS)was performed in all participants and analysis of fractional anisotropy(FA)within the whole brain was conducted in each participant.The relationship between the altered FA value and clinical variables was also analyzed.Results:1.Task-based fMRI: Compared with normal-sight controls,no matter for P-pathway or M-pathway visual stimulus,the BOLD signal in V1 show a pattern of amblyopic eye < non-amblyopic eye = non-dominant eye = dominant eye in both the amblyopic children and adults.Moreover,the peak of percentage BOLD signal change was significantly correlated with the corrected visual acuity of amblyopic eye in both the amblyopic children and adults.2.Resting-state fMRI: Compared with normal-sight controls,the amblyopic children mainly exhibited increased ALFF in visual area(left middle occipital gyrus and right superior occipital gyrus),but the amblyopic adults showed decreased ALFF in the bilateral posterior cingulate.Moreover,ALFF value of visual areas were significantly correlated with the corrected visual acuity of amblyopic eye in amblyopic children,whereas the ALFF value of bilateral posterior cingulate were correlated with the amount of anisometropia in amblyopic adults.3.Structural MRI for Gray Matter: Compared with normal-sight controls,the amblyopic children mainly exhibited increased cortical thickness in visual area(bilateral cuneus and left lingual gyrus),and the cortical thickness in these areas were significantly correlated with the corrected visual acuity of amblyopic eye.By contrast,there was no significant difference in cortical thickness between adult patients and controls.4.Structural MRI for White Matter: Compared with normal-sight controls,both the amblyopic children and adults showed significant decreased FA in visual related white matter fiber tracts(bilateral optic radiation and left inferior occipito-frontal fasciculus).In addition,the amblyopic adults even exhibited decreased FA in left splenium of corpus callosum.Moreover,the FA value of bilateral optic radiation were significantly correlated with the corrected visual acuity of amblyopic eye in both the amblyopic children and adults.Conclusion:1.Brain Function for Special Task: Both the amblyopic children and adults show V1 functional deficiency to M-pathway and P-pathway visual stimulus,suggesting that the functional deficiency in V1 is a critical part of the neural mechanism of amblyopia.2.Brain Function under Resting-state: Amblyopic children mainly show significant altered spontaneous brain activity in visual area,whereas amblyopic adults exhibit brain network impairment under resting-state.3.Brain Structure of Gray Matter: The normal cortical thickness thinning process(especially in the visual cortex)may be interrupted in amblyopic children,and cortical atrophy may occur subsequently in amblyopic adults due to the long course of disease.4.Brain Structure of White Matter: The normal myelinization process(especially in visual-related white matter fiber tracts)may be effected in amblyopic children and persist into adulthood.Moreover,the amblyopic adults even showed a disconnection between bilateral hemispheres.In conclusion,our findings demonstrate that not only the brain function but also the brain structure are changed both in children and adults with anisometropic amblyopia,giving us more insight into the neural mechanism of amblyopia.Moreover,our findings also reveal the differences in functional and structural brain alterations between the amblyopic children and adults,which may provide a preliminary explanation to the difference in treatment efficacy between them and an initiatory guidance to the treatment for amblyoic adults.