Hearing

Auditory processing in mammals begins in the peripheral inner ear and extends to the auditory cortex. Sound is transduced from mechanical stimuli into electrochemical signals of hair cells, which relay auditory information via the primary auditory neurons to cochlear nuclei. Information is subsequently processed in the superior olivary complex, lateral lemniscus, and inferior colliculus and projects to the auditory cortex via the medial geniculate body in the thalamus. Recent advances have provided valuable insights into the development and functioning of auditory structures, complementing our understanding of the physiological mechanisms underlying auditory processing. This comprehensive review explores the genetic mechanisms required for auditory system development from the peripheral cochlea to the auditory cortex. We highlight transcription factors and other genes with key recurring and interacting roles in guiding auditory system development and organization. Understanding these gene regulatory networks holds promise for developing novel therapeutic strategies for hearing disorders, benefiting millions globally.

The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus-pituitary-adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

BackgroundThere is slow progress in early hearing detection and intervention (EHDI) services within South Africa. Audiologists are EHDI gatekeepers and can provide valuable insights into the barriers and facilitators that can progressively move EHDI towards best practice in South Africa.ObjectivesThe study aimed to determine the barriers and facilitators to EHDI in KwaZulu-Natal as reported by audiologists/speech therapists and audiologists (A/STAs).MethodA descriptive qualitative approach was used. Telephonic interviews were conducted with 12 A/STAs working in public and private healthcare facilities, using the strengths, weaknesses, opportunities, threats (SWOT) conceptual framework. Data was analysed using thematic analysis in conjunction with NVivo software.ResultsOne of the main barriers perceived by A/STAs, affecting EHDI was the lack of resources in healthcare facilities. The participants indicated that although there was a guideline in place to guide practice, it may be more suited to an urban area versus a rural area. Poor knowledge and awareness of EHDI was also identified as a barrier. Information provided from A/STAs at grassroots level, in the various provinces, may benefit in developing a more contextually relevant and practical guideline. Facilitators included; development of task teams specifically for EHDI programmes, creation of improved communication networks for collaboration and communication, training of healthcare professionals and improving data management systems.ConclusionStrategies such as an increase in resources, further education and training, development of contextually relevant, culturally, and linguistically diverse practices and protocols need to be in place to improve EHDI implementation. Further research, clinical implications and limitations are provided emanating from the study.

Usher syndrome type III (USH3) is a genetic disorder characterized by progressive, post-lingual hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa. USH3 is caused by mutations in CLRN1, which encodes clarin-1, a tetraspanin-like protein. Mutations in CLRN2, which encodes the related protein clarin-2, are also implicated in progressive, non-syndromic hearing loss in both humans and mice. USH3 patients show considerable phenotypic variability, even among individuals with the same mutation. This variability may result from environmental factors or interactions with other inner ear genes, such as CLRN2. To investigate the functional interplay of these genes, we generated Clrn1- /-Clrn2-/- double knockout mice. RNA-sequencing and functional/physiological analyses revealed that clarin-1 and clarin-2 jointly regulate mechanoelectrical transduction, ionic homeostasis, and synaptic organization. Their combined loss leads to more severe hearing phenotype compared to Clrn1-/- and Clrn2-/- mice, which reveals a functional compensation between them. CLRN2 variants may exacerbate hearing loss in USH3 patients, supporting inclusion of CLRN2 in genetic screening. By revealing a functional, compensatory interplay between clarin-1 and clarin-2, this study reframes CLRN1-associated deafness as a network-dependent disorder and provides a mechanistic basis for genetic stratification and therapeutic directions in USH3 and related sensorineural hearing loss.