Objectives:Hearing loss in patients with sudden sensorineural hearing loss(SSHNL)can affect the central nervous system function,including both auditory and non-auditory cortices.However,the brain regions and networks involved in neural functional reorganization remain unclear.In this study,we used resting-state functional magnetic resonance imaging(rs-fMRI)technology to observe changes in local brain function and network connectivity after hearing loss in unilateral SSHNL patients during the acute phase,aiming to explore the neural plasticity mechanisms following SSHNL.Acupuncture is an important complementary therapy for the clinical treatment of SSNHL.A randomized controlled trial was conducted to longitudinally explore the influence of "Seven lines in the neck" of acupuncture on the central nervous plasticity in SSNHL patients.Methods:This study was divided into two parts.The first part was a case series study,including Study 1 and Study 2.In Study 1,patients with acute stage unilateral SSNHL who met the enrollment criteria(SSNHL group)and healthy controls(HC group)matching age and gender were included.Clinical data and rs-fMRI data were collected from both two groups,and amplitude of low-frequency fluctuation(ALFF)and regional homogeneity(ReHo)were performed on the rs-fMRI data to explore local brain functional activity changes in patients with unilateral SSNHL during the acute phase.In study 2,functional connectivity(FC)and independent component analysis(ICA)methods were used to explore the changes of brain networks and functional connectivity in networks.The second part was a randomized controlled trial,including Study 3 and Study 4.Eligible acute unilateral SSNHL patients were randomly assigned to either the "Seven lines in the neck" acupuncture combined with western medicine group(group 1)or the western medicine only group(group 2).Audiological assessment and accompanying tinnitus and emotional cognitive impairment were performed at the time of admission and 4 weeks after treatment,and rs-fMRI data were collected at the same time.In Study 3,we compared the differences in treatment efficacy among patients in intra-group and inter-group after treatment,and combined ALFF and ReHo analysis to explore the influence of "Seven lines in the neck" acupuncture on the local brain area of acute unilateral SSNHL patients and its correlation with clinical efficacy.In Study 4,FC and ICA analysis were used to compare intra-group and inter-group functional connectivity changes in brain networks after treatment in both groups,and explored the network characteristics and integrity of acupuncture treatment.Results:1.Comparison of general data,clinical indicators and brain function between SSNHL group and HC group(1)All subjects had unilateral hearing loss,were Han Chinese,right-handed,and there was no statistically significant difference in age or gender between the two groups(P>0.05),indicating comparability.(2)Comparison of ALFF and ReHo values:Compared to the HC group,the SSNHL group showed increased ALFF values in the left middle temporal gyrus,inferior temporal gyrus,insula,inferior parietal lobule,and right frontal lobe,while ALFF values was decreased in the right fusiform gyrus,middle temporal gyrus,superior temporal gyrus,superior limbic gyrus,lingual gyrus,and posterior central gyrus.The brain regions with increased ReHo values included left middle temporal gyrus,superior temporal gyrus,inferior frontal gyrus,middle frontal gyrus,insula,posterior central gyrus,and right inferior parietal lobule,while the regions with decreased ReHo values included the right middle temporal gyrus,inferior temporal gyrus,middle frontal gyrus,inferior frontal gyrus,posterior central gyrus,and left supraoccipital gyrus.Both ALFF and ReHo changes occurred in bilateral middle temporal gyrus and right posterior central gyrus.The correlation analysis showed that the ALFF values of the left middle temporal gyrus and inferior temporal gyrus in patients were positively correlated with pure tone average.The ReHo value of the left m iddle temporal gyrus was also positively correlated with pure tone average.while the ReHo value of the right middle frontal gyrus was negatively correlated with Tinnitus Handicap Inventory score.(3)Comparison of brain networks:Bilateral A1(Brodman41 area)was selected as the seed point.The FC with Al decreased in the left inferior parietal lobule,left inferior cerebellar lobule,right middle frontal gyrus,inferior frontal gyrus,right inferior temporal gyrus,and right fusiform gyrus,but no brain regions with increased FC were found.ICA analysis showed that the FC between pDMN and IFPN enhanced,while that between DAN and MVN decreased.2.Comparison of audiology indexes,emotional and cognitive impairment indexes and brain function indexes between group 1 and group 2 before and after intervention(1)Comparison of hearing threshold:In group I,there were statistically significant differences in the thresholds of all frequencies(0.25,0.5,1,2,4,8 kHz)after treatment(0.25 kHZ P=0.006,0.5 kHZ P=0.005,I kHZ P=0.010,2 kHZ P=0.027,4 kHz P=0.003 and 8kHz P=0.022).In group 2,there was a statistically significant difference in the hearing threshold of 8kHz(8kHz P=0.042),but no statistical difference in the hearing threshold of other frequencies(0.25 kHz P=0.106,0.5 kHz P=0.066,1 kHz P=0.098,2 kHz P=0.079,4 kHz P=0.054).The hearing gain in two groups showed no significant difference at any frequency(0.25 kHz P=0.271,0.5 kHz P=0.221,1 kHz P=0.294,2 kHz P=0.380,4 kHz P=0.189 and 8 kHz P=0.1 76).(2)Comparison of emotional and cognitive disorders:There were statistically significant differences in the Tinnitus Handicap Inventory score and Minimum Mental State Examination score between the groups(P<0.05),as well as in the Self-rating Depression Scale score and Self-rating Anxiety Scale score(P<0.01).(3)Comparison of ALFF and ReHo values:Before and after treatment in group I showed that,ALFF decreased in bilateral anterior cerebellar,left posterior cerebellar,triangular inferior frontal gyrus,and apex gyrus,while increased in the right orbital superior frontal gyrus,right superior temporal gyrus,right middle temporal gyrus,left precuneus,left cingulate gyrus,left talobiform cortex,bilateral cuneus,right superior margin gyrus,anterior central gyrus,and posterior central gyrus.The ReHo values in the cortex around the left orbitofrontal gyrus,left middle occipital gyrus,right lingual gyrus and bilateral taloid fissure increased.The ReHo values in left insula,parapedial gyrus and middle temporal gyrus decreased.Compared with group 2,the increased in ALFF in left inferior temporal gyrus,inferior frontal gyrus,middle frontal gyrus,fusiform gyrus,insula,and posterior central gyrus,while decreased in bilateral posterior cerebellar lobe,bilateral anterior cuneus lobe,left lingual gyrus,and left cingulate gyrus.The ReHo values increased in the right posterior central gyrus,right inferior temporal gyrus,right parahippocampal gyrus,right fusiform gyrus,left cingulate gyrus,left superior temporal gyrus,middle temporal gyrus,and left middle frontal gyrus,while decreased in the bilateral precuneus,cuneus,left superior frontal gyrus,right middle frontal gyrus,and left posterior cerebellar lobe.(4)Comparison of brain networks:After treatment the group 1 showed FC with A1 decreased in left subparietal lobule,and no increased FC was observed.ICA analysis showed widespread changes,including enhanced FC between LVN and aDMN,DAN,rFPN,as well as rFPN and MVN,but decreased FC between IFPN and pDMN in group 1 after treatment.The comparison between two groups showed decreased FC between the right inferior temporal gyrus,right inferior frontal gyrus,and A1,while increased FC between the left temporal lobe,right superior temporal gyrus and middle temporal gyrus,bilateral superior frontal gyrus,inferior frontal gyrus,left precuneus,and A1.ICA analysis showed enhanced FC between DAN and rFPN,pDMN and SMN,but decreased FC between IFPN and SMN,AN and SMN.Conclusions:1.The cerebral cortex of patients with acute unilateral SSNHL exhibits plastic changes,including the auditory cortex and non-auditory cortex,eg.frontal lobe and parietal lobe and occipital lobe.Among them,the level of neural activity in the medial temporal gyrus may serve as a potential imaging biomarker in SSNHL patients.2.Widespread FC changes occur in SSNHL patients during the acute phase.Although there may not show obvious clinical cognitive dysfunction in patients,their brain networks have already undergone extensive reorganization,which may be one of the pathological mechanisms of dementia after hearing loss.3."Seven lines in the neck"acupuncture combined with Western medicine can improve hearing level,mood and cognitive function in SSNHL patients,and its therapeutic effect is superior to that of Western medicine alone.4."Seven lines in the neck"acupuncture may improve hearing and related emotional and cognitive functions in SSNHL patients by regulating of temporal and fronto-parietal lobes.The"Seven lines in the neck"acupuncture can regulate the FC among auditory network,default network,attention network,fronto-parietal network and seusorimotor network,and its effects on patients’ brain function are relatively specific,bidirectional and network-based. |