Tinnitus and hyperacusis in children: clinic reports and basic research

Objective Tinnitus and hyperacusis are subjective symptoms which can be reponeu tJy p^t, lJ ： age. Although tinnitus and hyperacusis can have a negative effect on child development, these symptoms are commonly overlooked by their parents and clinicians. In this paper, we review clinical reports on tinnitus and hyperacusis in children and basic scientific studies on these disorders in order to provide updates of these disorders in the pediatric population. Recent studies have found that tinnitus and hyperacusis are not uncommon in children, especially in those with conductive and sensorineural hearing loss. The parents and clinicians should pay attention when children show abnormal behaviors and especially when they develop hearing loss. Since there is no objective measurement for tinnitus and hyperacusis, the diagnosis in children can be challenging. Tinnitus and hyperacusis are also common in Williams syndrome and autism but the mechanisms are still not clear. High doses of salicylate and noise exposure can in- duce tinnitus. Animal studies have determined lack of inhibition in the auditory cortex and the inferior colliculus may be critical for tinnitus and hyperacusis generation. The non-classic auditory system may also be involved in the aware- ness and tolerance of tinnitus and hyperacusis.

Hyperacusis and stapes surgery:An observation in fifty patients after stapedotomy

Objective:To assess hyperacusis after stapedotomy and its possible influencing factors.Study design:Prospective,interventional,and longitudinal study.Setting:A tertiary referral center.Patients:Fifty consecutive patients(35 females,mean age=46.8 years).Intervention:All patients underwent stapedotomy.The validated Portuguese version of the“Hyperacusis Questionnaire”(HQ)was administered before and two weeks and one month after surgery.Results:No hyperacusis was reported by any patient before surgery.At two weeks after surgery,all patients experienced hyperacusis,with a mean HQ at 16.88±6.54(range 4e25).One month after surgery,hyperacusis had already resolved in most patients.Gender,preoperative presentation or surgeon had no influence on HQ scores(p>0.05).Patients with previous contralateral stapedotomy showed lower HQ scores(p=0.001).Audiological parameters improvement measured at one month after surgery(PTA,SRT and contralateral SRT)were associated with HQ higher scores.Conclusion:This study confirms that hyperacusis is a common complaint after stapedotomy that usually resolves in one month after surgery.The HQ highest scores were registered among patients with the highest audiological gain after surgery.This suggests that hyperacusis may be a positive prognostic factor for audiological success after stapedotomy.

Acoustic trauma-induced auditory cortex enhancement and tinnitus

There is growing evidence suggests that noise-induced cochlear damage may lead to hyperexcitability in the central auditory system(CAS)which may give rise to tinnitus.However,the correlation between the onset of the neurophysiological changes in the CAS and the onset of tinnitus has not been well studied.To investigate this relationship,chronic electrodes were implanted into the auditory cortex(AC) and sound evoked activities were measured from awake rats before and after noise exposure.The auditory brainstem response(ABR) was used to assess the degree of noise-induced hearing loss.Tinnitus was evaluated by measuring gap-induced prepulse inhibition(gap-PPI).Rats were exposed monaurally to a high-intensity narrowband noise centered at 12 kHz at a level of 120 dB SPL for 1 h.After the noise exposure,all the rats developed either permanent(>2 weeks) or temporary(<3 days) hearing loss in the exposed ear(s).The AC amplitudes increased significantly 4 h after the noise exposure.Most of the exposed rats also showed decreased gap-PPI.The post-exposure AC enhancement showed a positive correlation with the amount of hearing loss.The onset of tinnitus-like behavior was happened after the onset of AC enhancement.

ACOUSTIC STARTLE RESPONSE AFFECTED BY AGING AND CHOLINERGIC NEUROTRANSMITTERS

The acoustic startle response has been used to evaluate tinnitus and hyperacusis in animal models. Gap induced prepulse in- hibition of the acoustic startle reflex （gap-PPI） is affected by tinnitus and loudness changes. Since tinnitus and reduced sound tolerance are commonly seen in elderly, we measured gap-PPI in Fischer 344 rats, an aging related hearing loss model, at dif- ferent agcs： 3-5 months, 9-12 months, and 15-17 months. The startle response was induced by three different intensity of sound： 105, 95 and 85 dB SPL. Gap-PPI was induced by different duration of silent gaps from 1 to 100 ms. When thc startle was induced by 105 dB SPL sound intensity, the gap-PPI induced by 50 ms silent gap was significantly lower than those in- duced by 25 or 100 ms duration, showing a ＂notch＂ in the gap-PPI function. The ＂notch＂ disappeared with the reduction of startle sound, suggesting the ＂notch＂ may be related with hyper-sensitivity to loud sound. As the intensity of the stimulus de- creased, the appearance of the hyperacusis-like effect decreased more quickly for the youngest group of rats. We also tested scopolamine, a muscarinic acetylcholine receptor antagonist, and mecamylamine, a nicotinic acetylcholine receptor antago- nist, on the effect of gap-PPI. When scopolamine was administered, the results indicated no addition effect on the hyperacu- sis-like phenomenon in the two older groups. Mecamylamine, the nicotinic antagonist also showed effects on the appearance of hyperacusis on rats in different ages. The information derived from the study will be fundamental for the further research in determining the cause and treatment for hyperacusis.

PERIPHERAL HEARING LOSS CAUSES HYPEREXCITABILITY OF THE INFERIOR COLLICULUS

Growing evidence has been found to suggest that early development of the central auditory system is dependent on acoustic stimuli. Peripheral damage caused by noise exposure and ototoxic drugs can induce functional and anatomical changes along the auditory pathways. The inferior colliculus (IC) is a unique structure in the auditory system located between the primary auditory nuclei of the brainstem and the thala-mus. Damage to the IC inhibitory circuitry may affect central auditory processing and sound perception. Here, we review some of the striking electrophysiological changes in the IC that occur after noise exposure and ototoxic drug treatment. A common occurrence that emerges in the IC after peripheral damage is hyper-excitability of sound-evoked response. The hyperexcitability of the IC is likely related with reduced inhibi-tory response that requires normal peripheral inputs. Early age hearing loss can result in a long lasting in-creased susceptibility to audiogenic seizure which is related to hyperactivity in the IC evoked by loud sounds. Our studies suggest that hearing loss can cause increased IC neuron responsiveness which may be related to tinnitus, hyperacusis, and audiogenic seizure.

Auditory symptoms and autistic spectrum disorder:A scoping review and recommendations for future research

Introduction:Auditory symptoms in individuals with Autistic Spectrum Disorder(ASD)are well described within the neurodevelopmental literature,yet there is minimal mention of ASD in Otolaryngology literature.This is surprising considering the potential clinical and diagnostic implications of this link,and the potential for ASD to present to Otolaryngologists in the form of unexplained auditory symptoms.The aims of this literature review were to explore the intersection of auditory symptoms and ASD from the perspective of clinical Otolaryngology,and to outline a clinically focused research agenda based on emerging themes relevant to Otolaryngology.Methods:We searched Pubmed,Embase,Ovid and Cochrane library for studies until November 2021.Four authors independently reviewed 227 publications identified.39 were filtered into the final analysis.The PRISMA 2020 guidelines were followed.The heterogeneity of literature meant that a Systematic Review was not feasible.Included studies were therefore classified thematically,forming the basis of the scoping review.Results:Diagnostic theories for auditory symptoms in ASD include the entire auditory pathway and brain.There is a growing body of literature on auditory symptoms in ASD,suggesting that a primary diagnosis of ASD should be considered in patients presenting with otherwise unexplained auditory symptoms,and indicating a learning need for Otolaryngologists and audiologists,to whom these patients may present.Conclusion:We recommend a research agenda focusing on multidisciplinary collaboration,stakeholder engagement,responsible clinical screening,and clarification of pathophysiological mechanisms and terminology.

Transient decrease in sound tolerance levels following hearing deprivation in normal-hearing subjects

Objective:To determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human subjects.Design:Participants underwent bilateral earplugging before completion of anthropometry,the author's developed questionnaire,the Hamilton Anxiety and Depression Inventory,pure tone audiometry(PTA),stapedial reflex thresholds(SRT),distortion products otoacoustic emissions input/output(DPOAE-I/O),and uncomfortable loudness levels(ULLs).Afterward,the participants were randomly divided into group A,starting at 8:00 a.m.and finishing at 8:00 p.m.,and group B,starting at 4:00 p.m.and ending at 4:00 a.m.Serum cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were measured.Study sample:Thirty healthy volunteers.Results:PTA was 2.68 and 3.33 dB HL in groups A and B,respectively,with no statistical difference between them.ULLs were significantly lower in group A compared to group B,with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B(p<0.0001).A SRT shift was observed in group A,with no difference in group B,and a night shift in DPOAE-I/O in group B.Conclusions:Reduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime;this may be due to increased central gain in the awake cortex.

FIRING PROPERTY OF INFERIOR COLLICULUS NEURONS AFFECTED BY FMR1 GENE MUTATION

Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn- drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the nor- mal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound （hyperacusis）. The molecular basis of fragile X syndrome is thoroughly understood; however, the neural mechanisms underly- ing hyperacusis have not yet been determined. As the inferior colliculus （IC） is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction ob- served within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.

Neurophysiological Manifestations of Auditory Hypersensitivity Correlate with Daily Life Experiences

Background: This study aimed to compare the neurophysiological responses to sound in adults with hypersensitivity compared to adults without hypersensitivity, and correlate the daily-life experiences to the neurophysiological manifestations. Material and Methods: The Adolescent/Adult Sensory Profile (AASP) was administered to 27 adults, separated by their cut-off scores. Differences in neurophysiological responses were measured by N1-P2 Event-Related Potentials (ERP) in response to auditory changes in frequency and intensity. Reactions to daily sounds were measured by the hyperacusis questionnaire. Correlations between AASP, hyperacusis questionnaire, and ERP were measured. Results: The basic ability to detect a change in stimuli manifested in N1 waveform was not significantly different. However, participants with hypersensitivity presented a stronger P2 response and a higher hyperacusis score. Daily expressions of auditory hypersensitivity correlated (p = 0.05 - p = 0.01) with larger ERP responses. Conclusions: Auditory hypersensitivity as reflected in daily scenarios is evident in neurophysiological manifestations measured by ERPs. Understanding the relationship between the neural mechanisms of auditory hyper-ensitivity and its daily expressions, may optimize participation and wellbeing for people with hypersensitivity.

听觉过敏及其干预

听觉过敏既涉及生理问题,也涉及心理问题,它是身心共同作用的一种临床表现。听觉过敏与恐声症（phonophobia）、厌声症（misphonia）、响度重振（recruitment）等表现相关联,用现代医学检查手段难以客观、严格的区别,但在临床上我们仍应细致观察,