Investigation Of The Neural Mechanisms Of Presbysusis With Cognitive Impairment Using Sub-bands Analysis Of ALFF And Functional Connectivity

Presbycusis(PC),also known as age-related hearing loss(ARHL),is one of the most common chronic diseases of the elderly.PC is characterized by preferential hearing loss at high frequencies and difficulty in speech recognition in noisy environments.With the accelerating aging of the global population,the number of PC patients is increasing year by year.It is estimated that by 2025,the population over 60-year-old will exceed 1.2 billion,among which more than 500 million will suffer from PC[1].Moreover,in recent years,a large number of epidemiological studies have shown that PC is closely related to cognitive impairment,and it is also an independent risk factor leading to and accelerating dementia in the elderly.In view of this phenomenon,some scholars put forward sensory-deprivation theory,which holds that PC patients need to call more cognitive resources to understand the speech information with weakened auditory signals,which may trigger cascading changes from the auditory cortex to the cognitive system in the long run,and then cause cognitive impairment.However,most of the previous studies on PC were limited to the cochlea,and the neural mechanism by which PC causes cognitive impairment has not yet been clarified.The rapid development of magnetic resonance imaging(MRI)provides a powerful tool to study the pathogenesis of nervous system diseases.Previous studies have found that there were structural and functional remodeling of the auditory cortex in PC patients,but whether there was neuroplasticity in cognitive-related brain regions and the relationship between the neuroplasticity and cognitive impairment remained unclear.What's more,whether there is a cascading change in the auditory cortex to cognitive system and the mode of change in the sensory-deprivation theory remain unclear.Therefore,this study aims to study the functional neuroplasticity of PC patients by using the amplitude of low-frequency fluctuation(ALFF)at different frequency bands in local spontaneous brain activity level,the changes of functional connectivity between auditory cortex and other brain regions by using seed-based analysis,the changes of functional connectivity within and between networks by using independent component analysis(ICA),so as to analyze the relationship between imaging changes and auditory and cognitive function scores,providing support for the sensory-deprivation theory and revealing the neural mechanism of cognitive impairment in PC patients.PART ?.Investigation of Brain Functional Plasticity in Patients with Presbycusis Using Sub-bands Analysis of ALFFObjective Functional magnetic resonance imaging(fMRI)was used to study the functional neuroplasticity of PC patients by using the amplitude of low-frequency fluctuation(ALFF)at bands of slow-4 and slow-5,so as to reflect the change of local brain nerve activity.To investigate its correlation with cognitive impairment,and to explore the neuroplasticity of brain regions related to hearing and cognition in PC patients.Materials and methods Fifty-one PC patients and fifty-one well-matched normal hearing controls participated in this study.Assessment of auditory and cognitive function were performed respectively.Multimodal MRI data were collected for data preprocessing.The LFO amplitudes were investigated using the amplitude of low-frequency fluctuation(ALFF)at different frequency bands(slow-4 and slow-5 bands).Functional connectivity analysis was performed using the seed-based approach.Regions that exhibited significant ALFF differences between the PC and NH groups were used as seeds in the subsequent FC analysis.Finally,partial correlation analyses were performed to explore the potential relationships between the mean ALFF within regions that exhibited significant group differences and cognitive function or audiological outcomes in the PC and NH groups(controlled for age,sex,education level).Results The comparisons between PC and NH groups showed some similarities in the two frequency bands,such as decreased ALFF in the bilateral precuneus and the right PCC,as well as increased ALFF in the right ITG in the PC patients in both bands(slow-4 and slow-5 bands).In contrast,some obvious differences also existed between the two bands.There was decreased ALFF in the bilateral putamen;the right SOG,AG,SMG,FEF and paracentral lobule;the left PCC,IPG,DLPFC and SMA,along with increased ALFF in the left HG in PC patients compared to the controls in slow-4 band,changes which were not seen in the slow-5 band.In the PC group,partial correlation analyses revealed that Stroop scores were negatively correlated with the ALFF of the left IPG;TMT-B scores were negatively correlated with the ALFF of the left ITG;SDMT scores were positively associated with the ALFF of the right SMG.AVLT scores were positively associated with the ALFF of the left HG.In the NH group,no correlations were observed between clinical characteristics and ALFF.Conclusion In this study,it was found that abnormal spontaneous neural activity in PC patients was frequency dependent and correlated with cognitive impairment.Frequency specific analysis of ALFF can provide a detailed exploration of spontaneous neural activities in the auditory cortex and cognitive-related cortex of PC patients,and provide theoretical basis for the mechanism of cognitive impairment in PC patients.Imaging markers of cognitive impairment in PC patients can be found at the level of brain regions.PART ?.Investigation of Functional Connectivity Plasticity in Patients with Presbycusis Using Seed-based AnalysisObjective Functional magnetic resonance imaging(fMRI)was used to analyze the changes in functional connectivity between the region of interest(ROI)and all brain voxels,using seed-based functional connectivity Analysis,as well as the correlation between FC changes and hearing and cognitive assessment scores,in order to explore the neuroplasticity in PC patients at the functional connectivity level.Materials and Methods The subjects were the same as Part ?(Including fifty-one PC patients and fifty-one well-matched normal hearing controls).Assessment of auditory and cognitive function were performed respectively.Multimodal MRI data were collected for data preprocessing.First,bilateral primary auditory cortex(Heschl's gyrus)was selected as seed regions in PC patients.Then,the brain regions with abnormal ALFF in PC patients in the first part were used as seed regions.RSET toolbox was used to extract the functional connections between each seed region and all the voxels in the whole brain.Finally,partial correlation analyses were performed to assess the relationship between FC values in areas with significant inter-group differences in the PC and NH groups and indicators of cognitive and auditory function(controlled for age,sex,education level).Results With HG as the seed regions,compared with the NH group,the FC between right HG and left fusiform gyrus,left superior temporal gyrus,left middle temporal gyrus,left anterior cingulate gyrus,right insular lobe,right putamen,right middle cingulate gyrus and bilateral posterior central gyrus were significantly decreased in PC group.There was no significant difference in the FC between left HG and other voxels in the whole brain in PC group compared with NH group.In PC group,the FC between right HG and right insula was significantly negatively correlated with PTAand SRT.With dlPFC as the seed region,compared with the NH group,the dlPFC showed stronger FC with the temporal pole,STG,cuneus,middle occipital gyrus(MOG),precentral gyrus,SMA and inferior frontal gyrus(IFG)in PC group.In PC group,the FC between right HG and right insular lobe was negatively correlated with PTA and SRT.Stroop scores was negatively correlated with the FC between dlPFC and left IFG,and TMT-A scores was negatively correlated with the FC between dlPFC and the left temporal pole.In the NH group,no correlations were observed between clinical characteristics and FC of dlPFC.Conclusion In PC patients,the FC between the auditory cortex and cognitive-related brain regions changed.There was enhanced FC between dlPFC and sensory-motor regions and posterdorsal stream of auditory processing,and it was associated with cognitive impairment.These results suggest that auditory and cognitive-related brain regions are remodeled at the level of functional connectivity in PC patients.PART ?.Investigation of Brain Network Plasticity in Patients with Presbycusis Using Independent Component AnalysisObjective This study explored the alterations in intra-and inter-network functional connectivity(FC)of multiple networks in PC patients,by ICA-based functional connectivity analysis,as well as the correlation between FCs changes and hearing and cognitive assessment scores,in order to explore the neuroplasticity in PC patients at network level.Materials and Methods The subjects were the same as Part ?(Including fifty-one PC patients and fifty-one well-matched normal hearing controls).Assessment of auditory and cognitive function were performed respectively.Multimodal MRI data were collected for data preprocessing.12 resting-state networks(RSNs)were identified by independent component analysis(ICA)approach.The FCs among multiple nodes(brain regions)of each resting-state network were calculated,and the results of FCs within the network were obtained.The low-frequency oscillation characteristics of all voxels in a network are averaged,and the FCs with other networks are calculated,and the FCs between networks are obtained.The intra-and inter-network FC changes and their relationship with neuropsychological assessment results were calculated by one way Analysis Of Variance(ANOVA)and regression analysis.Results 12 RSNs were identified by using ICA,including auditory network(AN),default mode network(DMN),anterior default mode network(aDMN),posterior default mode network(pDMN),visual network(VN),sensory motor network(SMN),left executive control network(IECN),right executive control network(rECN),salience network(SN)?+?,dorsal attention network(DAN)and basal ganglia network(BGN).Compared to the NH group,there were significantly decreased intra-network FCs in the DMN and ECN.There were also decreased inter-network FCs between AN and DMN,SN and aDMN,VN and BGN,as well as increased inter-network FCs between VN and AN,VN and SMN,the left VN and AN.Conclusions Multiple functional changes of RSNs in patients with PC were confirmed,including primary sensory cortex and advanced cognitive network.The intra-and inter-network connectivity results revealed a cross-modal neuroplasticity in PC patients and a top-down control in auditory information processing.These results revealed the presence of neuroplasticity in brain network in PC patients,and it was associated with cognitive impairment.