The Neural Plasticity Of Long Term Bilateral Sensorineural Hearing Loss Using Multimodal MRI

Part 1 Dissociation between cerebellar and cerebral neural activities in humans with long term bilateral sensorineural hearing lossObjectives: Abnormal neural activity in the cerebellum has been implicated in hearing impairments,but the effects of long-term hearing loss on cerebellar function are poorly understood.This study was conducted to further explore the role of long term bilateral sensorineural hearing loss on cerebellar function and investigated hearing loss-induced changes among neural networks within cerebellar subregions and the changes in cerebellar-cerebral connectivity patterns using resting-state functional MRI.Materials and Methods: Twenty-one subjects with long term bilateral sensorineural hearing loss and 21 age-,sex-,body mass index-,and education level-,matched controls with clinically normal hearing underwent pure tone audiometry test,MRI scanning and a series of neuropsychological tests targeting cognition and emotion.The neuropsychological tests were mini-mental state examination(MMSE),auditory verbal learning test(AVLT),symbol digit modalities test(SDMT),self-rating anxiety scale(SAS)and Hamilton depression scale(HAMD).Results: Voxel-wise functional connectivity(FC)analysis demonstrated decreased couplings between the cerebellum and other cerebral areas,including the temporal pole(TP),insula,supramarginal gyrus,inferior frontal gyrus(IFG),medial frontal gyrus,and thalamus,in long term bilateral sensorineural hearing loss patients.An ROI-wise FC analysis found weakened interregional connections within cerebellar subdivisions.Moreover,there was a negative correlation between anxiety and left cerebellar lobe VI-left insula FC.Hearing ability and anxiety scores were also correlated with FC between the left cerebellar lobe VI and left TP,as well as the FC between the right cerebellar lobule VI and left IFG.Conclusions: These results suggest that sensorineural hearing loss disrupts cerebellar-cerebral circuits,some potentially linked to anxiety,and interregional cerebellar connectivity.The current study contribute to a growing body showing that auditory deprivation caused by cochlear hearing loss disrupts not only activity with the classical auditory pathway but also portions of the cerebellum that communicates with other cortical networks.Part 2 Altered spatial and temporal brain connectivity in the salience network of sensorineural hearing lossObjectives: The salience network,which is anchored in bilateral anterior insula and dorsal anterior cingulate cortex,has been implicated in sensory integration.Partial auditory deprivation could alter the characteristics of the salience network and other related brain areas,thereby contributing to hearing impairments induced neuropsychiatric symptoms.Materials and Methods: To test this hypothesis,f MRI scanning and neuropsychological tests were performed on 32 subjects with long term bilateral hearing impairment and 30 well-matched Controls.Non-directional functional connectivity and directional Granger causality analysis were used to identify aberrant spatial and temporal patterns of connections targeting bilateral anterior insula and dorsal anterior cingulate cortex.Results: The left anterior insula showed decreased connectivity with right precentral gyrus and superior frontal gyrus.The connections between the dorsal anterior cingulate cortex and middle frontal gyrus,superior parietal gyrus and supplementary motor area(SMA)were also reduced.Relative to Controls,SNHL patients showed abnormal effective connectivity of the salience network,including inferior temporal gyrus,cerebellum lobule VI,lobule VIII,precentral gyrus,middle frontal gyrus and SMA.Furthermore,correlation analysis demonstrated that some of these atypical connectivity measures were correlated with performance of neuropsychiatric tests.Conclusions: These findings suggest that the inefficient modulation of the salience network might contribute to the neural basis of SNHL,as well as associated cognition and emotion deficits.Part 3 Inefficient involvement of insula in sensorineural hearing lossObjectives: The insular cortex plays an important role in multimodal sensory processing,audiovisual integration and emotion.However,little is known about how the insula is affected by auditory deprivation due to SNHL.Structural and functional MRI were computed to determine the role of insula.Materials and Methods: Thirty-five SNHL subjects and 54 Controls enrolled in this study underwent auditory evaluation,neuropsychological assessments,functional and structure MRI,respectively.Twenty five patients and 20 Controls underwent arterial spin labeling(ASL)scanning.FC of six insula subdivisions were assessed and the FC results were compared to the neuropsychological tests.Interregional connections were also compared among insula-associated networks,including the salience network,default mode network and central executive network.Results: Compared to Controls,SNHL subjects demonstrated hyperperfusion in the insula and a significant reduction in FC between the left ventral anterior insula(v AI)and the bilateral thalamus and right precentral gyrus.Additionally,the SNHL group displayed weakened FC between left dorsal anterior insula(dAI)and the right thalamus,putamen,dorsolateral prefrontal cortex(DLPFC),precentral gyrus,postcentral gyrus and mid-cingulate cortex.Moreover,the SNHL group demonstrated decreased FC between the right dAI and right rolandic operculum.Finally,the SNHL group demonstrated decreased FC between the right posterior insula(PI)and right thalamus,as well as right precentral gyrus.FC of the left dAI and right DLPFC was negatively correlated with anxiety level(r =-0.489,p = 0.005)and positively correlated with SDMT sores(r = 0.410,p = 0.020).FC in the left dAI and the right mid-cingulate cortex FC was negatively correlated with HAMD scores(r =-0.402,p = 0.022).Abnormal interactions among the salience network,default mode network,and central executive network were observed in SNHL group.Conclusions: Our result provides support for the “inefficient high-order control” theory of the insula in which the auditory deprivation caused by SNHL contributes to impaired sensory integration and central deficits in emotional and cognitive processing.Part 4 Sensorineural hearing loss and cognitive Impairments: contributions of thalamus using multimodal MRIObjectives: The thalamus is an integrative hub conveying sensory information between cortical areas and related to cognition.However,alterations of the thalamus following partial hearing deprivation remains unknown.The purpose is to investigate the modifications of the thalamus and its seven subdivisions in terms of structure,function,and perfusion in subjects with SNHL,as well as their associations with SNHL-induced cognitive impairments.Materials and Methods: 37 subjects with long-term bilateral SNHL and 38 gender-,age-,body mass index-,and education level-matched controls were included in this study.Quantitative measurements in the thalamus and subdivisions were obtained,including the relative volume,fALFF values within slow 5(0.01–0.027 Hz),slow 4(0.027–0.073 Hz),and combined frequency(0.01–0.073 Hz),as well as the whole brain connectivity.Twenty-five SNHL patients and 20 controls underwent ASL scanning.Then correlation analysis was computed between all significant changes and cognition tests.Continuous and categorical variables were compared by independent-sample t-test and chi-square test,respectively.Quantitative MRI measurement comparisons were corrected for multiple comparison,and FC analysis used two-sample t-test with false-discovery rate correction.The AUC in ROC analysis was applied to evaluate the power of alterations in differentiating SNHL and controls.Results: No significant difference in the relative volume and perfusion of seven thalamus subdivisions were observed,but a decrease in fALFF in SNHL.the left prefrontal thalamus showed weakened connectivity with the left cerebellum lobule VIII,ventral anterior cingulate cortex(v ACC),insula,and superior temporal gyrus(STG)in the SNHL group.The voxel-wise analysis revealed group differences in the right prefrontal thalamus connectivity with the left cerebellum lobe VIII,insula,medial frontal gyrus,Heschl's gyrus,and media temporal gyrus,as well as right temporal pole,STG,and insula.Meanwhile,the left temporal thalamus and left v ACC connectivity also decreased in the SNHL compared with the controls.And some FC abnormalities exhibited positive correlations with cognitive tests and high discriminative power(0.8 < AUC < 1)in two groups.Conclusions: SNHL led to decreased thalamic activity and widespread weakened connectivity with other brain areas.