Maojin Liang

SIRT1 expression in the cochlea and auditory cortex of a mouse model of age-related hearing loss.

SIRT1 is a highly conserved NAD(+)-dependent protein deacetylase known to have protective effects against a variety of age-related diseases. However, there is a lack of information concerning SIRT1 expression in the cochlea and auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss. Using RT-PCR and immunohistochemistry, we show that SIRT1 is abundantly expressed in the inner hair cells, strial marginal cells, strial intermediate cells, type I and type IV fibrocytes of the spiral ligament and spiral ganglion neurons. In addition, moderate SIRT1 is also detected in the outer hair cells and neurons of the auditory cortex. Associated with elevated hearing thresholds and hair cells loss during aging, there is also a significant reduction of SIRT1 expression in the cochlea and auditory cortex. The expression pattern of SIRT1 in the peripheral and central auditory system suggests that SIRT1 may play an important role in auditory function and therefore may serve as a protective molecule against age-related hearing loss.

Evaluation of auditory cortical development in the early stages of post cochlear implantation using mismatch negativity measurement

Objective The aim of this study was to investigate auditory cortical development using mismatch negativity (MMN) in prelingual severe-to-profound hearing-impaired children from the stage of cochlear implant (CI) power-up to 6 months after power-up. Method Eighteen children were recruited and examined at the stage of CI initial power-up (M0), as well as several follow-up periods, that is, 1 month (M1), 3 months (M3), and 6 months (M6) after CI power-up. The MMN responses were measured using a 128-Channel Dense Array EEG System. The group average and individual MMN analysis were used to investigate the longitudinal changes of the MMN characteristics. The relationship between MMN characteristics and scores of categories of auditory performance (CAP) was also investigated. Results Although the MMN incidence was much lower at the periods of M0 and M1, significantly higher MMN incidence was found in M3 and M6. The MMN latencies decreased significantly from M3 to M6, but no significant difference in the amplitudes was found between these periods. There was a negative correlation between the increment of CAP scores and decrement of MMN latency from M3 to M6. Conclusion MMN incidence increment and latency decrement are likely to be the objective and noninvasive indicators for evaluating auditory central development at an early stage in children after cochlear implantation. Moreover, the latency decrement from M3 to M6 correlated significantly with the increment of the CAP scores, indicating a fast maturation period, which might be a key period for auditory rehabilitation.

Auditory Spatial Discrimination and the Mismatch Negativity Response in Hearing-Impaired Individuals

The aims of the present study were to investigate the ability of hearing-impaired (HI) individuals with different binaural hearing conditions to discriminate spatial auditory-sources at the midline and lateral positions, and to explore the possible central processing mechanisms by measuring the minimal audible angle (MAA) and mismatch negativity (MMN) response. To measure MAA at the left/right 0°, 45° and 90° positions, 12 normal-hearing (NH) participants and 36 patients with sensorineural hearing loss, which included 12 patients with symmetrical hearing loss (SHL) and 24 patients with asymmetrical hearing loss (AHL) [12 with unilateral hearing loss on the left (UHLL) and 12 with unilateral hearing loss on the right (UHLR)] were recruited. In addition, 128-electrode electroencephalography was used to record the MMN response in a separate group of 60 patients (20 UHLL, 20 UHLR and 20 SHL patients) and 20 NH participants. The results showed MAA thresholds of the NH participants to be significantly lower than the HI participants. Also, a significantly smaller MAA threshold was obtained at the midline position than at the lateral position in both NH and SHL groups. However, in the AHL group, MAA threshold for the 90° position on the affected side was significantly smaller than the MMA thresholds obtained at other positions. Significantly reduced amplitudes and prolonged latencies of the MMN were found in the HI groups compared to the NH group. In addition, contralateral activation was found in the UHL group for sounds emanating from the 90° position on the affected side and in the NH group. These findings suggest that the abilities of spatial discrimination at the midline and lateral positions vary significantly in different hearing conditions. A reduced MMN amplitude and prolonged latency together with bilaterally symmetrical cortical activations over the auditory hemispheres indicate possible cortical compensatory changes associated with poor behavioral spatial discrimination in individuals with HI.

Toward an Understanding of Auditory Evoked Cortical Event-Related Potentials: Characteristics and Classification

Abstract Objective: To investigate the characteristics of auditory evoked cortical ERP components P1-N1-P2 and MMN and explore a practical way for ERP waveform identification and classification. Methods: Thirty right-handed normally hearing volunteers participated in the present study, age ranging from 20 to 40 years old, 14 males and 16 females. All the volunteers reported no history of auditory, neurological or mental disorder. The event related potential (ERP) components (i.e. P1-N1-P2 complex and mismatch negativity (MMN)) were measured using the 128-electrode channels EGI system. Results: Three different categories of ERP responses were classified on the basis of waveform configuration, size of the peak amplitude and the number of peaks together with scalp distribution of MMN. Ten participants (33.3%) had well defined ERP responses, 13 (43.3%) showed moderately defined ERP responses, and seven (23.3%) had poorly defined ERP responses. Although there were no significant differences in P1, P2, and MMN latencies, participants with the poorly defined ERP waves had significantly longer N1 latency than that in subjects with well defined ERP waves. In addition, significantly lower MMN amplitudes were also found in this group. Conclusion: Combining a waveform classification method and the MMN scalp distribution pattern, together with quantitative ERP response analysis, may provide more reliable and practical means for clinical application.

Effect of the combination of balloon Eustachian tuboplasty and tympanic paracentesis on intractable chronic otitis media with effusion

OBJECTIVE To evaluate the effect of the combination of balloon Eustachian tuboplasty (BET) and tympanic paracentesis (TP) on intractable chronic otitis media with effusion (COME). METHODS Ninety patients with intractable COME were included and randomly assigned to three groups: BET only (30 patients), BET+paracentesis (30 patients), and paracentesis only (30 patients). Otic endoscopic findings and tympanograms were recorded before the surgery and at the month 1, month 3, and month 6 follow-up evaluations. RESULTS Both the BET only and BET+paracentesis groups achieved better outcomes than the paracentesis group. The BET+paracentesis group exhibited better otic endoscopic scores than the BET only group (p<0.05) at 1month post-operation. However, no significant difference was found at month 3 or month 6 post-operation. No significant difference in the tympanograms was observed between these two groups at month 1, month 3, or month 6 post-operation. The otic endoscopic sign scores improved from month 1 to month 6 in the BET only group and from month 1 to month 3 in the BET+paracentesis group. The conversion of type B tympanograms improved from month 1 to month 6 in the BET and BET+paracentesis groups but not in the paracentesis only group. CONCLUSIONS Our results suggested that the combination of BET and TP was effective for intractable COME and can help shorten the recovery period for middle ear effusion.

Visual cortex activation decrement following cochlear implantation in prelingual deafened children

OBJECTIVE Visual take-over of the auditory cortex in prelingual deaf children has been widely reported. However, there have been few studies on visual cortex plasticity after cochlear implantation (CI). In this study, we investigated the hypothesis that extrinsic auditory stimulation following CI in prelingual deafened children can induce visual cortex plasticity. METHOD Visual evoked potentials (VEPs) were recorded in 37 CI children (4 groups with different use times) and 8 control subjects, in response to sound and nonsound stimuli. Latency and amplitude were analyzed for the P1, N1 and P2 components on the Oz electrode. Comparisons of VEP were conducted between the sound and nonsound stimuli and among different groups in order to view evidence of visual cortex reorganization. RESULTS The latency of the P2 component was significantly longer at the occipital site (Oz) in CI 0M than those in the other four groups. After the effect of age was excluded, a significant negative correlation was found between CI usage and P2 latency of nonsound stimuli. Occipital P1N1 latency and P1 amplitude were not affected by group or stimulus category. However, the N1 and P2 amplitudes were significantly larger in response to a sound stimulus than to a nonsound stimulus. CONCLUSION Our findings suggest that P2 latency develops with CI usage and may be a biomarker of visual cortex plasticity.

Higher-Order Brain Network Analysis for Auditory Disease

Auditory diseases such as deafness and tinnitus have been plaguing people for a long time. On the one hand, although cochlear implantation may serve as a cure for deafness to some degree, the mechanism of developmental neuroplasticity in the auditory and visual systems has not been well understood. On the other hand, there is still no cure for tinnitus, and investigating the cause and then developing the cure of tinnitus is particularly necessary. EEG signals provide us insights into these auditory diseases and have been widely studied for developing the cure of auditory diseases, in particular from the brain network perspective. However, most of the existing methods either simply utilize lower-order features of the brain network at the level of local connections within selected brain regions or fail to analyze the EEG signals from the brain region connectivity perspective. In this paper, based on the EEG signals, we develop a new higher-order brain network analysis method termed HBNmining (higher-order brain network mining) based on the weighted motifs and colored motifs for deepening the understanding of the auditory diseases. In particular, after constructing brain network from EEG signals, both the weighted motifs and the colored motifs are extracted, from which subject classification and brain region connectivity analysis can be conducted respectively. The results have confirmed the effectiveness of our method, which may be helpful for clinical treatment of auditory diseases.

TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation

Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1β and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation.

Plasma brain-derived neurotrophic factor levels are increased in patients with tinnitus and correlated with therapeutic effects.

Tinnitus is the perception of sound without an external source and is known to be associated with altered neuronal excitability in the auditory system. Tinnitus severity can be assessed by various psychometric instruments and there is no objective measures developed to evaluate tinnitus severity and therapeutic effects so far. Brain-derived nerve growth factor (BDNF) is believed in playing a key role in regulating neuronal excitability in the brain. To determine whether BDNF correlates with tinnitus induction and severity, we described plasma BDNF levels in patients with tinnitus and healthy controls and evaluated the correlation between plasma BDNF levels and tinnitus severity measured by Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Moreover, alteration of plasma BDNF levels before and after tinnitus retraining therapy (TRT) in patients with severe tinnitus was also analyzed. We found plasma BDNF levels were elevated in patients with tinnitus compared with healthy controls. In addition, plasma BDNF levels in patients with severe tinnitus were decreased significantly after effective TRT. However, plasma BDNF levels were not correlated with tinnitus loudness and tinnitus severity measured by THI and VAS. These findings support plasma BDNF as a marker for activity changes in the auditory system and could possibly evaluate therapeutic effects in patients with tinnitus.

Cholesterol Granuloma of the Middle Ear in Post-Irradiated Nasopharyngeal Carcinoma Patients

Background/Aims: To evaluate the surgical outcome of tympanoplasty with mastoidectomy for cholesterol granuloma of the middle ear in post-irradiated patients with nasopharyngeal carcinoma (NPC). Methods: Nine post-irradiated NPC patients diagnosed with cholesterol granuloma in a single-sided middle ear were included in this study. The time from radiotherapy termination to surgery ranged from 6 to 14 years (median 9 years). All patients underwent radical tympanoplasty with canal wall down or up mastoidectomy. Results: All the patients with NPC received radiotherapy of 68–75 Gy before surgery. Three ears underwent tympanoplasty with canal wall down mastoidectomy, and 6 ears underwent tympanoplasty with canal wall up mastoidectomy. All the patients were followed up for at least 2 years. Seven ears (77.8%) had an intact tympanic membrane and 2 ears developed re-perforation of the eardrum 3 months after surgery, but otorrhea decreased significantly. All these patients reported improved quality of life after surgery. Before the operation, the pure tone averages (0.25, 0.5, 1, 2 kHz) were 90.5 dB and the air-bone gaps (0.5, 1, 2 kHz) were 45.8 dB (vs. 62.3 and 25.5 dB, respectively, at 6 months after the operation). Conclusions: Most post-irradiated NPC patients with cholesterol granuloma of the middle ear benefit from this surgery. Chronic otitis media caused by radiotherapy is not a contraindication to tympanoplasty.