| Part 1: Dynamic functional remodeling in a long-term high-frequency noise-induced hearing loss rat modelObjective: Hearing loss makes great impact on the structure and the function of the central nervous system,however where,when and how the changes of neural plasticity occur remain poorly understood.Here we took advantage of multiple analysis techniques of resting-state functional magnetic resonance imaging(rs-f MRI)to map the dynamical functional remodeling pattern across the central nervous system,with the very focus of the cross-modal reorganization,potential functional mechanism underlying hearing loss-related cognitive deficits,and topological reconfiguration of the brain complex network in hearing loss.Methods: SD rats were exposed by a narrow-band high-frequency noise(16 k Hz-20 k Hz,102 d B,24h/day)constantly for 5 weeks to establish a high-frequency hearing loss rat model.Auditory brainstem response tests were employed at one week and six months after noise exposure to measure the hearing thresholds.Rs-f MRI data were obtained one-day,one-month and three-month post-exposure for each of the rats.Contextual fear conditioning test and cued fear conditioning test were also conducted three-month post-exposure.Results: Permanent high-frequency hearing threshold shifts were observed in rats of noise exposure(NE)group.Ganger causality analysis revealed that prefrontal cortex showed higher net Granger causal flow to visual cortex in the NE group in relative to control group threemonth post-exposure.Voxel-wise functional connectivity(FC)analysis showed wider decreases in FC of dorsal hippocampus(i.e.,cognitive subdivision of hippocampus)in the NE group over time after exposure,involving multiple sensory processing regions,prefrontal cortex,nucleus accumbens and thalamus.Meanwhile,the rats in the NE group showed fear-associative memory deficits when compared to the control group three-month post-exposure.Finally,a loss of small-world architecture and lower local efficiency were found in the functional network of rats in NE group three-month post-exposure.Conclusions: prefrontal cortex may mediate the cross-modal organization between auditory and visual modalities after hearing loss.Hippocampal network dysconnectivity presumably contributes to the cognitive dysfunction related to hearing loss.The functional remodeling following hearing loss not only involves specific brain areas or system,but also leads to topological reconfiguration which influences the capability and efficiency of information transformation,integration and processing across the global brain.Part 2: Dorsolateral prefrontal cortex mediates the crossmodal and cognitive reorganization of auditory cortex in long-term sensorineural hearing lossObjective: The participant of auditory cortex into other sensory and higher-order cognitive processing has been well known in hearing loss,however,the exact mechanism is still unclear.Dorsolateral prefrontal cortex(dl PFC),with intense connections to auditory system,plays an important role in auditory regulation,multi-sensory integration,and cognitive control.This study was to assess whether dl PFC mediates the recruitment of auditory cortex in cross-modal and cognitive reorganization in sensorineural hearing loss(SNHL).Methods: 35 bilateral chronic SNHL patients and 35 well-matched healthy controls underwent the multi-modal MRI scanning,and Symbol Digit Modalities Test(SDMT)to measure their attention,visual tracking and working memory,and processing speed.Results: Analyses of multi-modal MRI metrics did not reveal any between-group difference in amplitude of low-frequency fluctuation(ALFF),grey matter volume,fractional anisotropy(FA)or mean diffusivity(MD)of dl PFC.The functional connectivity(FC)of dl PFC in auditory and visual cortices was significantly increased in the SNHL group compared to healthy control group.dl PFC FC in auditory cortex was correlated with the SDMT scores in the patients with SNHL.Voxel-wise hearing-related FC analysis revealed positive association between dl PFC FC to visual cortex with mean hearing thresholds of the patients with SNHL.Decreased FA was found in the SNHL group relative to healthy control group via tract-based spatial statistics(TBSS),particularly in the temporal part of inferior fronto-occipital fasciculus(IFOF),where the mean FA value was negatively associated with the mean hearing thresholds of SNHL patients.Conclusions: Increased functional synchrony between dl PFC and auditory and visual cortices,together with decreased FA in temporal IFOF connecting frontal and occipito-temporal area,suggest that dl PFC probably mediates cross-modal reorganization through top-down regulation,and facilitates the recruitment of auditory cortex into cognitive processing in the case of hearing loss.Part 3: Hippocampal dysconnectivity in patients with longterm sensorineural hearing lossObjective: Hearing loss has a significant association with cognitive decline,and is one of the independent risk factors of dementia.The neural mechanism underlying such association is still uncertain.This study aimed to identify the relationship between hippocampal abnormalities and cognitive dysfunction of long-term SNHL patients based on resting-state functional MRI.Methods: 38 bilateral SNHL patients and 39 well-matched healthy controls were included in this study.Structural and resting-state functional MRI data were acquired.The functional alterations in hippocampus were assessed via voxel-based functional connectivity(FC)and global functional connectivity(GFC).Linear regression models were employed to test the associations between the aberrant hippocampal FC and the Auditory Verbal Learning Test(AVLT)scores in patients with SNHL.Results: Compared to healthy controls,patients with SNHL showed significantly lower hippocampal FC in multiple sensory cortices and parts of prefrontal cortex.GFC of hippocampus was also decreased in the SNHL group.Hippocampal GFC was positively associated with AVLT immediate and short-term delayed recall scores in patients with SNHL.Conclusions: Hearing loss influences functional coupling of hippocampus with structurally or functionally connected brain areas.Abnormal hippocampal network connectivity is potentially linked to the cognitive dysfunction in SNHL.Our findings provide insights into functional mechanisms underlying the hearing loss-related cognitive deficits.Part 4: Resting-state functional network reorganization in patients with long-term sensorineural hearing lossObjective: Hearing loss makes great impacts on memory,attention and executive function of the patients,suggestive of the existence of high-order functional network remodeling in auditory-deprived brain.To identify the pattern of the network reconfiguration in the case of hearing loss,we assessed the functional connectivity properties of the resting-state functional networks in patients with long-term SNHL.Methods: This study included 34 long-term bilateral SNHL patients and 34 healthy controls with well-matched age,gender and education.All subjects underwent resting-state f MRI scanning and cognition-related neuropsychological assessments.Independent component analysis(ICA)method was used to define 11 resting-state networks(RSNs).Inter-network functional connectivity(FC)was compared between two groups.Associations between abnormal inter-network FC involving high-order functional networks and cognitive function in patients with SNHL were determined by linear regression models.Then,by constructing a whole-brain complex network,we calculated and compared the properties of small-worldness and network efficiency.Results: Compared to healthy controls,SNHL patients showed extensive inter-network functional reconfiguration across the 11 RSNs,involving low-level sensory processing networks(e.g.,sensory-motor network and visual network)and high-order cognitive control networks(e.g.,default mode network,attention network,frontal-parietal network).The abnormal inter-network FC of these high-order cognitive control networks are related to the cognitive scores in SNHL patients.Whole-brain complex network of SNHL patients has a weaker small-world architecture.Conclusions: The network plasticity changes in the case of long-term hearing loss does not only involve the low-level sensory processing networks,but also the extensive high-order cognitive control networks,as well as the topological configuration of the whole-brain complex network.The functional remodeling of the brain network could be a putative neural mechanism underlying cognitive dysfunction in patients with SNHL,and even affects the capability and efficiency of information processing,transmission,and integration across the global brain network. |
PDF Full Text Request