Glymphatic System Dysfunction in Congenital Sensorineural Hearing Loss: A DTI-ALPS Study.

BACKGROUND: The neural mechanisms underlying congenital sensorineural hearing loss (CSNHL) remain elusive. OBJECTIVE: This study evaluated the function of the glymphatic system in children with CSNHL compared to normal-hearing children using the DTI-ALPS approach, which utilizes diffusion tensor imaging along the perivascular space. METHODS: Twenty-six children with CSNHL and 30 age- and sex-matched healthy controls (HCs) with normal hearing thresholds were recruited. The DTIALPS index was calculated for each group. We analyzed the discrepancies in the DTI-ALPS index between patients with CSNHL and healthy controls. Additionally, Spearman's correlation analysis was performed to investigate the relationship between the DTI-ALPS index and age in children with CSNHL. RESULTS: Significant differences in the DTI-ALPS index were observed between the two groups. Compared with HCs, the DTI-ALPS index in CSNHL patients was significantly lower (1.49388±0.11441 vs. 1.61402±0.15430, p=0.002). In addition, diffusivity along the z-axis in the association fiber (Dzzassoc) index was significantly higher in the CSNHL group than in the HC group (0.00041±0.00006 vs. 0.00036±0.00004, p=0.003). Furthermore, we discovered a noteworthy downward correlation between the DTI-ALPS index and age in children with CSNHL (rho = -0.544, p=0.005). CONCLUSION: In this present study, glymphatic system activity in CSNHL children was investigated for the first time using the DTI-ALPS index. A significant decrease in glymphatic system function was detected in CSNHL children, which correlated well with age. The DTI-ALPS index could serve as a valuable biomarker for tracking disease progression and treatment in CSNHL and unraveling the neural mechanisms of early hearing deprivation in children with CSNHL.

Abnormal cerebellar network and effective connectivity in sudden and long-term sensorineural hearing loss.

Sudden sensorineural hearing loss (SSNHL) is a common otology emergency and some SSNHL will develop into a long-term hearing loss (LSNHL). However, whether SSNHL and LSNHL have similar psychiatric patterns remains unknown, as well as the neural substrates. Increasing evidence has proved that the cerebellar network plays a vital role in hearing, cognition processing, and emotion control. Thus, we recruited 20 right SSNHL (RSSNHL), 20 right LSNHL (RLSNHL), and 24 well-matched healthy controls to explore the cerebellar patterns among the three groups. Every participant underwent pure tone audiometry tests, neuropsychological evaluations, and MRI scanning. Independent component analysis (ICA) was carried out on the MRI data and the cerebellar network was extracted. Granger causality analysis (GCA) was conducted using the significant cerebellar region as a seed. Pearson's correlation analysis was computed between imaging characteristics and clinical features. ICA found the effect of group on right cerebellum lobule V for the cerebellar network. Then, we found decreased outflow from right cerebellum lobule V to right middle orbitofrontal cortex, inferior frontal gyrus, anterior cingulate cortex, superior temporal gyrus, and dorsal lateral prefrontal cortex in RSSNHL group in GCA analysis. No significance was found in RLSNHL subjects. Additionally, the RSSNHL group showed increased effective connectivity from the right middle frontal gyrus (MFG) and the RLSNHL group showed increased effective connectivity from the right insula and temporal pole to the right cerebellum lobule V. Moreover, connections between right cerebellum lobule V and mean time series of the cerebellar network was negatively correlated with anxiety score in RSSNHL and negatively correlated with depression scores in RLSNHL. Effective connectivity from right MFG to right cerebellum lobule V could predict anxiety status in RSSNHL subjects. Our results may prove potential imaging biomarkers and treatment targets for hearing loss in future work.

Aberrant Functional Network of Small-World in Sudden Sensorineural Hearing Loss With Tinnitus.

Few researchers investigated the topological properties and relationships with cognitive deficits in sudden sensorineural hearing loss (SNHL) with tinnitus. To explore the topological characteristics of the brain connectome following SNHL from the global level and nodal level, we recruited 36 bilateral SNHL patients with tinnitus and 37 well-matched healthy controls. Every subject underwent pure tone audiometry tests, neuropsychological assessments, and MRI scanning. AAL atlas was employed to divide a brain into 90 cortical and subcortical regions of interest, then investigated the global and nodal properties of "small world" network in SNHL and control groups using a graph-theory analysis. The global characteristics include small worldness, cluster coefficient, characteristic path length, local efficiency, and global efficiency. Node properties include degree centrality, betweenness centrality, nodal efficiency, and nodal clustering coefficient. Interregional connectivity analysis was also computed among 90 nodes. We found that the SNHL group had significantly higher hearing thresholds and cognitive impairments, as well as disrupted internal connections among 90 nodes. SNHL group displayed lower AUC of cluster coefficient and path length lambda, but increased global efficiency. The opercular and triangular parts of the inferior frontal gyrus, rectus gyrus, parahippocampal gyrus, precuneus, and amygdala showed abnormal local features. Some of these connectome alterations were correlated with cognitive ability and the duration of SNHL. This study may prove potential imaging biomarkers and treatment targets for future studies.

Specific brain network predictors of interventions with different mechanisms for tinnitus patients.

BACKGROUND: The aberrant brain network that gives rise to the phantom sound of tinnitus is believed to determine the effectiveness of tinnitus therapies involving neuromodulation with repetitive transcranial magnetic stimulation (rTMS) and sound therapy utilizing tailor-made notch music training (TMNMT). To test this hypothesis, we determined how effective rTMS or TMNMT were in ameliorating tinnitus in patients with different functional brain networks. METHODS: Resting-state functional MRI was used to construct brain functional networks in patients with tinnitus (41 males/45 females, mean age 49.53±11.19 years) and gender-matched healthy controls (22 males/35 females, mean age 46.23±10.23 years) with independent component analysis (ICA). A 2 × 2 analysis of variance with treatment outcomes (Effective group, EG/Ineffective group, IG) and treatment types (rTMS/TMNMT) was used to test the interaction between outcomes and treatment types associated with functional network connections (FNCs). FINDINGS: The optimal neuroimaging indicator for responding to rTMS (AUC 0.804, sensitivity 0.700, specificity 0.913) was FNCs in the salience network-right frontoparietal network (SN-RFPN) while for responding to TMNMT (AUC 0.764, sensitivity 0.864, specificity 0.667) was the combination of FNCs in the auditory network- salience network (AUN-SN) and auditory network-cerebellar network (AUN-CN). INTERPRETATION: Tinnitus patients with higher FNCs in the SN-RFPN is associated with a recommendation for rTMS whereas patients with lower FNCs in the AUN-SN and AUN-CN would suggest TMNMT as the better choice. These results indicate that brain network-based measures aid in the selection of the optimal form of treatment for a patient contributing to advances in precision medicine. FUNDING: Yuexin Cai is supported by Key R&D Program of Guangdong Province, China (Grant No. 2018B030339001), National Natural Science Foundation of China (82071062), Natural Science Foundation of Guangdong province (2021A1515012038), the Fundamental Research Funds for the Central Universities (20ykpy91), and Sun Yat-Sen Clinical Research Cultivating Program (SYS-Q-201903). Yu-Chen Chen is supported by Medical Science and Technology Development Foundation of Nanjing Department of Health (No. ZKX20037), and Natural Science Foundation of Jiangsu Province (No. BK20211008).

Arterial Spin Labeling Cerebral Perfusion Changes in Chronic Tinnitus With Tension-Type Headache.

Purpose: Tinnitus is along with tension-type headache that will influence the cerebral blood flow (CBF) and accelerate the tinnitus severity. However, the potential associations between tension-type headache and tinnitus is still unknown. The current study will explore whether abnormal CBF exists in tinnitus patients and examine the effects of headache on CBF in tinnitus patients. Materials and Methods: Resting-state perfusion magnetic resonance imaging was performed in 40 chronic tinnitus patients and 50 healthy controls using pseudocontinuous arterial spin labeling. Regions with CBF differences between tinnitus patients and healthy controls were investigated. The effects of headache on tinnitus for CBF changes were further explored. Correlation analyses revealed the relationship between CBF values and tinnitus distress as well as CBF values and headache degree. Results: Relative to healthy controls, chronic tinnitus showed decreased CBF, mainly in right superior temporal gyrus (STG), left middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); the CBF in the right STG and the left MFG was negatively correlated with THQ scores (r = -0.553, p = 0.001; r = -0.399, p = 0.017). We also observed a significant effect of headache on tinnitus for CBF in the right STG. Furthermore, the headache degree was correlated positively with tinnitus distress (r = 0.594, p = 0.020). Conclusion: Decreased CBF in auditory and prefrontal cortex was observed in chronic tinnitus patients. Headache may accelerate CBF reductions in tinnitus, which may form the basis for the neurological mechanism in chronic tinnitus with tension-type headache.

Aberrant cerebral blood flow in tinnitus patients with migraine: a perfusion functional MRI study.

PURPOSE: Migraine is often accompanied with chronic tinnitus that will affect the cerebral blood flow (CBF) and exacerbate the tinnitus distress. However, the potential relationship between migraine and tinnitus remains unclear. This study will investigate whether aberrant CBF patterns exist in migraine patients with tinnitus and examine the influence of migraine on CBF alterations in chronic tinnitus. MATERIALS AND METHODS: Participants included chronic tinnitus patients (n = 45) and non-tinnitus controls (n = 50), matched for age, sex, education, and hearing thresholds. CBF images were collected and analyzed using arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between tinnitus patients and non-tinnitus controls were first detected. The effects of migraine on tinnitus for CBF alterations were further examined. Correlation analyses illustrated the association between CBF values and tinnitus severity as well as between CBF and severity of migraine. RESULTS: Compared with non-tinnitus controls, chronic tinnitus patients without migraine exhibited decreased CBF, primarily in right superior temporal gyrus (STG), bilateral middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); decreased CBF in these regions was correlated with tinnitus distress. There was a significant effect of migraine on tinnitus for CBF in right STG and MFG. Moreover, the severity of migraine correlated negatively with CBF in tinnitus patients. CONCLUSIONS: Chronic tinnitus patients exhibited reduced CBF in the auditory and prefrontal cortex. Migraine may facilitate a CBF decrease in the setting of tinnitus, which may underlie the neuropathological mechanisms of chronic tinnitus comorbid with migraine.