Auditory Sensitivity Research Articles

Auditory change detection and visual selective attention: association between MMN and N2pc.

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.

Microanatomy of the human tunnel of Corti structures and cochlear partition-tonotopic variations and transcellular signaling.

Auditory sensitivity and frequency resolution depend on the optimal transfer of sound-induced vibrations from the basilar membrane (BM) to the inner hair cells (IHCs), the principal auditory receptors. There remains a paucity of information on how this is accomplished along the frequency range in the human cochlea. Most of the current knowledge is derived either from animal experiments or human tissue processed after death, offering limited structural preservation and optical resolution. In our study, we analyzed the cytoarchitecture of the human cochlear partition at different frequency locations using high-resolution microscopy of uniquely preserved normal human tissue. The results may have clinical implications and increase our understanding of how frequency-dependent acoustic vibrations are carried to human IHCs. A 1-micron-thick plastic-embedded section (mid-modiolar) from a normal human cochlea uniquely preserved at lateral skull base surgery was analyzed using light and transmission electron microscopy (LM, TEM). Frequency locations were estimated using synchrotron radiation phase-contrast imaging (SR-PCI). Archival human tissue prepared for scanning electron microscopy (SEM) and super-resolution structured illumination microscopy (SR-SIM) were also used and compared in this study. Microscopy demonstrated great variations in the dimension and architecture of the human cochlear partition along the frequency range. Pillar cell geometry was closely regulated and depended on the reticular lamina slope and tympanic lip angle. A type II collagen-expressing lamina extended medially from the tympanic lip under the inner sulcus, here named "accessory basilar membrane." It was linked to the tympanic lip and inner pillar foot, and it may contribute to the overall compliance of the cochlear partition. Based on the findings, we speculate on the remarkable microanatomic inflections and geometric relationships which relay different sound-induced vibrations to the IHCs, including their relevance for the evolution of human speech reception and electric stimulation with auditory implants. The inner pillar transcellular microtubule/actin system's role of directly converting vibration energy to the IHC cuticular plate and ciliary bundle is highlighted.

Investigation on the contribution of swim bladder to hearing in crucian carp (Carassius carassius).

The swim bladder in some teleost fish functions to transfer the sound energy of acoustic stimuli to the inner ears. This study uses the auditory evoked potential tests, micro-computed tomography scanning, reconstruction, and numerical modeling to assess the contribution of the swim bladder to hearing in crucian carp (Carassius carassius). The auditory evoked potential results show that, at the tested frequency range, the audiogram of fish with an intact swim bladder linearly increases, ranging from 100 to 600 Hz. Over this frequency, the sound pressure thresholds have a local lowest value at 800 Hz. The mean auditory threshold of fish with an intact swim bladder is lower than that of fish with a deflated swim bladder by 0.8-20.7 dB. Furthermore, numerical simulations show that the received pressure of the intact swim bladders occurs at a mean peak frequency of 826 ± 13.6 Hz, and no peak response is found in the deflated swim bladders. The increased sensitivity of reception in sound pressure and acceleration are 34.4 dB re 1 μPa and 40.3 dB re 1 m·s-2 at the natural frequency of swim bladder, respectively. Both electrophysiological measurement and numerical simulation results show that the swim bladder can potentially extend hearing bandwidth and further enhance auditory sensitivity in C. carassius.

Hearing and vocalizations in a small songbird, the red-cheeked cordon bleu (Uraeginthus bengalus) (L).

The auditory sensitivity of a small songbird, the red-cheeked cordon bleu, was measured using the standard methods of animal psychophysics. Hearing in cordon bleus is similar to other small passerines with best hearing in the frequency region from 2 to 4 kHz and sensitivity declining at the rate of about 10 dB/octave below 2 kHz and about 35 dB/octave as frequency increases from 4 to 9 kHz. While critical ratios are similar to other songbirds, the long-term average power spectrum of cordon bleu song falls above the frequency of best hearing in this species.

EEG resting state alpha dynamics predict an individual’s vulnerability to auditory hallucinations

AbstractTask-free brain activity exhibits spontaneous fluctuations between functional states, characterized by synchronized activation patterns in distributed resting-state (RS) brain networks. The temporal dynamics of the networks’ electrophysiological signatures reflect individual variations in brain activity and connectivity linked to mental states and cognitive functions and can predict or monitor vulnerability to develop psychiatric or neurological disorders. In particular, RS alpha fluctuations modulate perceptual sensitivity, attentional shifts, and cognitive control, and could therefore reflect a neural correlate of increased vulnerability to sensory distortions, including the proneness to hallucinatory experiences. We recorded 5 min of RS EEG from 33 non-clinical individuals varying in hallucination proneness (HP) to investigate links between task-free alpha dynamics and vulnerability to hallucinations. To this end, we used a dynamic brain state allocation method to identify five recurrent alpha states together with their spatiotemporal dynamics and most active brain areas through source reconstruction. The dynamical features of a state marked by activation in somatosensory, auditory, and posterior default-mode network areas predicted auditory and auditory-verbal HP, but not general HP, such that individuals with higher vulnerability to auditory hallucinations spent more time in this state. The temporal dynamics of spontaneous alpha activity might reflect individual differences in attention to internally generated sensory events and altered auditory perceptual sensitivity. Altered RS alpha dynamics could therefore instantiate a neural marker of increased vulnerability to auditory hallucinations.

Auditory Sensitivity in Primitive Anurans of the Genus Discoglossus

Auditory Sensitivity in Primitive Anurans of the Genus Discoglossus

Size matters: individual variation in auditory sensitivity may influence sexual selection in Pacific treefrogs (Pseudacris regilla).

The matched filter hypothesis proposes a close match between senders and receivers and is supported by several studies on variation in signal properties and sensory-processing mechanisms among species and populations. Importantly, within populations, individual variation in sensory processing may affect how receivers perceive signals. Our main goals were to characterize hearing sensitivity of Pacific treefrogs (Pseudacris regilla), assess patterns of individual variation in hearing sensitivity, and evaluate how among-individual variation in hearing sensitivity and call frequency content affect auditory processing of communication signals. Overall, males and females are most sensitive to frequencies between 2.0 and 2.5kHz, which matches the dominant frequency of the call, and have a second region of high sensitivity between 400 and 800Hz that does not match the fundamental frequency of the call. We found high levels of among-individual variation in hearing sensitivity, primarily driven by subject size. Importantly, patterns of among-individual variation in hearing differ between males and females. Cross-correlation analyses reveal that among-individual variation in hearing sensitivity may lead to differences on how receivers, particularly females, perceive male calls. Our results suggest that individual variation in sensory processing may affect signal perception and influence the evolution of sexually selected traits.

Study of Speech Recognition in Noise and Working Memory in Adults and Elderly with Normal Hearing

Abstract Introduction In clinical practice, patients with the same degree and configuration of hearing loss, or even with normal audiometric thresholds, present substantially different performances in terms of speech perception. This probably happens because other factors, in addition to auditory sensitivity, interfere with speech perception. Thus, studies are needed to investigate the performance of listeners in unfavorable listening conditions to identify the processes that interfere in the speech perception of these subjects. Objective To verify the influence of age, temporal processing, and working memory on speech recognition in noise. Method Thirty-eight adult and elderly individuals with normal hearing thresholds participated in the study. Participants were divided into two groups: The adult group (G1), composed of 10 individuals aged 21 to 33 years, and the elderly group (G2), with 28 participants aged 60 to 81 years. They underwent audiological assessment with the Portuguese Sentence List Test, Gaps-in-Noise test, Digit Span Memory test, Running Span Task, Corsi Block-Tapping test, and Visual Pattern test. Results The Running Span Task score proved to be a statistically significant predictor of the listening-in-noise variable. This result showed that the difference in performance between groups G1 and G2 in relation to listening in noise is due not only to aging, but also to changes in working memory. Conclusion The study showed that working memory is a predictor of listening performance in noise in individuals with normal hearing, and that this task can provide important information for investigation in individuals who have difficulty hearing in unfavorable environments.

Auditory sensitivity and tympanic middle ear in a vocal and a non-vocal frog

The tympanic middle ear is important for anuran hearing on land. However, many species have partly or entirely lost their tympanic apparatus. Previous studies have compared hearing sensitivities in species that possess and lack tympanic membranes capable of sound production and acoustic communication. However, little is known about how these hearing abilities are comparable to those of mutant species. Here, we compared the eardrum and middle ear anatomies of two sympatric sibling species from a noisy stream habitat, namely the “non-vocal” Hainan torrent frog (Amolops hainanensis) and the “vocal” little torrent frog (Amolops torrentis), the latter of which is capable of acoustic communication. Our results showed that the relative (to head size) eardrum diameter of A. hainanensis was smaller than that of A. torrentis, although the absolute size was not smaller. Unlike A. torrentis, the tympanic membrane area of A. hainanensis was not clearly differentiated from the surrounding skin. The middle ear, however, was well-developed in both species. We measured the auditory brainstem responses (ABRs) of A. hainanensis and compared the ABR thresholds and latencies to those previously obtained for A. torrentis. Our results suggested that these two species exhibited significant differences in hearing sensitivity. A. hainanensis (smaller relative eardrum, nonvocal) had higher ABR thresholds and longer initial response times than A. torrentis (larger relative eardrum, vocal) at lower frequencies. Neurophysiological responses from the brain were obtained for tone pips between 800 Hz and 7,000 Hz, with peak sensitivities found at 3,000 Hz (73 dB SPL) for A. hainanensis, and at 1,800 Hz (61 dB SPL) for A. torrentis. Our results suggest that the non-vocal A. hainanensis has lower hearing sensitivity than its vocal sister species (i.e., A. torrentis), which may be related to differences in tympanic or inner ear structure and morphology.

Quantifying sensory thresholds along the migraine cycle: An exploratory longitudinal study.

To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity. This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month). Patients reported an increased sensitivity to light (padj = 0.0297), touch (padj = 0.0077), and smell (padj = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high (padj = 1.4e-06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity (padj = 1.4e-06). Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.

Listening and Processing Skills in Young School Children with a History of Developmental Phonological Disorder

There is a lack of longitudinal studies on the broad-based outcomes in children with Developmental Phonological Disorder (DPD). The aim of this study was to investigate listening and processing skills in a clinical sample of 7-to-10-year-old children diagnosed with DPD in their preschool years and compare these to same-aged typically developing (TD) children. The Evaluation of Children’s Listening and Processing Skills (ECLiPS) was completed by parents of 115 children with DPD and by parents of 46 TD children. The total ECLiPS mean score, and the five subscale mean scores, the proportion of children with clinically significant difficulties (≤10th percentile), and the proportion of children with co-occurrence of clinically significant difficulties on more than one subscale, were calculated. Results showed that the ECLiPS mean scores did not differ between the groups. There was no difference between groups regarding language and literacy, but a higher proportion of children with DPD than TD had difficulties in the total score, speech, and auditory processing, environmental and auditory sensitivity, and pragmatic and social skills. In addition, 33.9% of children with DPD had clinically significant difficulties in two or more subscales compared to 10.9% of TD children.

Associations Between Auditory Working Memory, Self-Perceived Listening Effort, and Hearing Difficulty in Adults With Mild Traumatic Brain Injury.

Mild traumatic brain injury (TBI) can have persistent effects in the auditory domain (e.g., difficulty listening in noise), despite individuals having normal pure-tone auditory sensitivity. Individuals with a history of mild TBI often perceive hearing difficulty and greater listening effort in complex listening situations. The purpose of the present study was to examine self-perceived hearing difficulty, listening effort, and performance on an auditory processing test battery in adults with a history of mild TBI compared with a control group. Twenty adults ages 20 to 53 years old participated divided into a mild TBI (n = 10) and control group (n = 10). Perceived hearing difficulties were measured using the Adult Auditory Processing Scale and the Hearing Handicap Inventory for Adults. Listening effort was measured using the National Aeronautics and Space Administration-Task Load Index. Listening effort ratings were obtained at baseline, after each auditory processing test, and at the completion of the test battery. The auditory processing test battery included (1) dichotic word recognition, (2) the 500-Hz masking level difference, (3) the Listening in Spatialized Noise-Sentences test, and (4) the Word Auditory Recognition and Recall Measure (WARRM). Results indicated that individuals with a history of mild TBI perceived significantly greater degrees of hearing difficulty and listening effort than the control group. There were no significant group differences on two of the auditory processing tasks (dichotic word recognition or Listening in Spatialized Noise-Sentences). The mild TBI group exhibited significantly poorer performance on the 500-Hz MLD and the WARRM, a measure of auditory working memory, than the control group. Greater degrees of self-perceived hearing difficulty were significantly associated with greater listening effort and poorer auditory working memory. Greater listening effort was also significantly associated with poorer auditory working memory. Results demonstrate that adults with a history of mild TBI may experience subjective hearing difficulty and listening effort when listening in challenging acoustic environments. Poorer auditory working memory on the WARRM task was observed for the adults with mild TBI and was associated with greater hearing difficulty and listening effort. Taken together, the present study suggests that conventional clinical audiometric battery alone may not provide enough information about auditory processing deficits in individuals with a history of mild TBI. The results support the use of a multifaceted battery of auditory processing tasks and subjective measures when evaluating individuals with a history of mild TBI.

Comparative Blood Transcriptome Analysis of Semi-Natural and Controlled Environment Populations of Yangtze Finless Porpoise.

The Yangtze finless porpoises (Neophocaena asiaeorientalis asiaeorientalis) living in different environments display significant differences in behavior and physiology. To compare and analyze gene expression differences between an ex situ population and a controlled environment population of the Yangtze finless porpoise, we sequenced the transcriptome of blood tissues living in a semi-natural reserve and an artificial facility, respectively. We identified 6860 differentially expressed genes (DEGs), of which 6603 were up-regulated and 257 were down-regulated in the controlled environment vs ex situ comparison. GO and KEGG enrichment analysis showed that the up-regulated genes in the controlled environment population were significantly associated with glucose metabolism, amino acid metabolism, and the nervous system, while those up-regulated in the ex situ population were significantly associated with energy supply and biosynthesis. Further analysis showed that metabolic and hearing-related genes were significantly affected by changes in the environment, and key metabolic genes such as HK, PFK, IDH, and GLS and key hearing-related genes such as OTOA, OTOF, SLC38A1, and GABBR2 were identified. These results suggest that the controlled environment population may have enhanced glucose metabolic ability via activation of glycolysis/gluconeogenesis, the TCA cycle, and inositol phosphate metabolism, while the ex situ population may meet higher energy requirements via enhancement of the amino acid metabolism of the liver and muscle and oxidative phosphorylation. Additionally, the acoustic behavior and auditory-related genes of Yangtze finless porpoise may show responsive changes and differential expression under different environment conditions, and thus the auditory sensitivity may also show corresponding adaptive characteristics. This study provides a new perspective for further exploration of the responsive changes of the two populations to various environments and provides a theoretical reference for further improvements in conservation practices for the Yangtze finless porpoise.

Diversity of sound production and hearing in fishes: Exploring the riddles of communication and sensory biology

My research in fish bioacoustics started in the mid-1980s and comprised the diversity in sound-generating mechanisms and sound production in various contexts such as dyadic contests. I worked on European freshwater and marine fish, but mainly on tropical fish from Southeast Asia (gouramis) and the Amazonian River system (pimelodid, doradid catfishes, piranhas). The diversity of sonic organs raised the question if general patterns of innervation of sonic muscles in vocal fishes exist. Different vocal (sonic) motor nuclei were identified in the brainstem and rostral spinal cord for pectoral and swim bladder vibration mechanisms. In addition, I wanted to find out if vocal fish differ from nonvocal species in hearing abilities. Measurements applying the auditory evoked potential technique revealed a large diversity of auditory sensitivities depending on the presence or lack of accessory hearing structures independently of sound production. Furthermore, I investigated the anatomy, ultrastructure of inner ears, and hearing enhancement by auxiliary hearing structures. Recently, we studied sound-induced motion of swim bladders, auditory ossicles, and otoliths using x-ray phase contrast imaging. A large part of my studies was carried out in cooperation with laboratories in the USA, Germany, Italy, Portugal, and Brasilia which made my research interesting.

Impact of SNR, peripheral auditory sensitivity, and central cognitive profile on the psychometric relation between pupillary response and speech performance in CI users.

Despite substantial technical advances and wider clinical use, cochlear implant (CI) users continue to report high and elevated listening effort especially under challenging noisy conditions. Among all the objective measures to quantify listening effort, pupillometry is one of the most widely used and robust physiological measures. Previous studies with normally hearing (NH) and hearing-impaired (HI) listeners have shown that the relation between speech performance in noise and listening effort (as measured by peak pupil dilation) is not linear and exhibits an inverted-U shape. However, it is unclear whether the same psychometric relation exists in CI users, and whether individual differences in auditory sensitivity and central cognitive capacity affect this relation. Therefore, we recruited 17 post-lingually deaf CI adults to perform speech-in-noise tasks from 0 to 20 dB SNR with a 4 dB step size. Simultaneously, their pupillary responses and self-reported subjective effort were recorded. To characterize top-down and bottom-up individual variabilities, a spectro-temporal modulation task and a set of cognitive abilities were measured. Clinical word recognition in quiet and Quality of Life (QoL) were also collected. Results showed that at a group level, an inverted-U shape psychometric curve between task difficulty (SNR) and peak pupil dilation (PPD) was not observed. Individual shape of the psychometric curve was significantly associated with some individual factors: CI users with higher clinical word and speech-in-noise recognition showed a quadratic decrease of PPD over increasing SNRs; CI users with better non-verbal intelligence and lower QoL showed smaller average PPD. To summarize, individual differences in CI users had a significant impact on the psychometric relation between pupillary response and task difficulty, hence affecting the interpretation of pupillary response as listening effort (or engagement) at different task difficulty levels. Future research and clinical applications should further characterize the possible effects of individual factors (such as motivation or engagement) in modulating CI users' occurrence of 'tipping point' on their psychometric functions, and develop an individualized method for reliably quantifying listening effort using pupillometry.

Experimental study on the effect of sound stimulation on hearing and behavior of juvenile black rockfish (Sebastes schlegelii)

Assessing the potential impacts of wind farm noise on fish is a crucial aspect of Environmental Impact Assessment (EIA) studies. There is increasing evidence of disturbances and effects on hearing and behavior in animals. The black rockfish (Sebastes schlegelii) is a commercially valuable rocky reef fish native to East Asia. However, empirical studies that measure the actual consequences are lacking. In this study, we used auditory evoked potentials (AEP) to assess the effects of dominant frequency noise emitted by offshore wind farms on the auditory sensitivity, hearing threshold, swimming, and feeding behavior of juvenile black rockfish. The experimental findings revealed that the most sensitive sound frequency was 200 Hz, with the lowest hearing threshold recorded at 86.4 ± 3.4 dB re 1 μPa. Following 3 and 7 days of exposure to 200 Hz noise at 110 dB, threshold shifts in black rockfish reached 19.0 dB and 13.3 dB, respectively. During the subsequent recovery phase, these shifts decreased to approximately 9.8 dB after 3 days, respectively. The noise-exposed group exhibited higher swimming duration, moving distance, and caudal fin swing frequency compared to the control group without noise exposure. Furthermore, noise prolonged the feeding rate of black rockfish. Our findings provide the first evidence of noise-induced temporary threshold shift and behavioral disturbances in juvenile black rockfish, implying potential fitness consequences associated with noise pollutant.

​​Auditory Sensitivity in Autism Spectrum Disorder: Assessment, Challenges, and Therapeutic Approaches

In recent years, our understanding of autism spectrum disorders (ASD) has evolved, allowing us to better understand and treat those affected by it. ASD affects behavior, physical aspects, and social development in millions of individuals nationwide. Among ASD the challenges faced by individuals with ASD, hyperacusis (reduced sound tolerance) is commonly found. This paper examines ASD's link to auditory sensitivity, especially hyperacusis, covering symptoms, causes, and interventions. Interventions such as cognitive behavioral therapy (CBT) and desensitization methods show promising results in alleviating symptoms of those with ASD. In conclusion, tailored approaches are needed for complex ASD challenges and treatment varies by individual. In order to better treat ASD, more research must be done to better understand the etiology and intricacies of this disorder. This paper emphasizes the significance of understanding ASD nuances and auditory aspects, promoting research for enhanced autism spectrum lives.

Effect of sound absorption on performance in cognitive tasks: Focusing on characteristics of subjects with developmental disabilities

Children with developmental disabilities often experience hearing-related difficulties in learning environments. Despite this, there has been little consideration given to acoustic design for these children in Japan. The aim of this study is to investigate how ambient noise affects the cognitive performance of individuals with developmental disabilities, and to examine whether sound absorption in the room can help mitigate any negative effects. To conduct the experiment, college students were randomly selected instead of children with developmental disabilities, due to ethical considerations. Subjects completed four cognitive tasks under a loud noise level of approximately 80 dB, which was assumed to be a corresponding condition experienced by children with auditory sensitivity. The results showed that the condition with sound-absorbing in the room resulted in higher scores overall. Subjects with developmental disabilities tended to score lower than those without, and tended to score relatively higher on some cognitive tasks under conditions where sound-absorbing material was installed. While further study is needed, these findings suggest that using sound-absorbing materials may have a positive impact on individuals with developmental disabilities.

Age-related changes of auditory sensitivity across the life span of CBA/CaJ mice

The inbred mouse strain CBA/CaJ is a frequently used animal model of age-related hearing loss in humans. These mice display significant hearing loss at a relatively advanced age, similar to most humans, with progressive loss of hearing as the mouse continues to age. While important descriptions of hearing loss in this mouse strain at multiple ages have previously been published, shortcomings persist in the data for hearing over the lifespan of the mouse. Therefore, we analyzed auditory brainstem response threshold data from records maintained by our research group to yield an extensive database of thresholds over nearly the entire life span of the CBA/CaJ mouse (from 79 to 1085 days). Data was collected from in-house bred mice of CBA/CaJ stock, initially from The Jackson Laboratory. Data was collected using BiosigRZ software and TDT System III hardware. Thresholds were routinely measured in conjunction with behavioral and electrophysiological experiments; only responses from baseline or experimentally naïve animals were analyzed. The resulting data set comprised 376 female mice and 441 males. At the lowest and highest frequencies (8 & 32 kHz), initial thresholds were just under 30 dB SPL and increased slowly until they were significantly different at 16-18 months compared to 1-3 months age, with the difference increasing over subsequent ages. At the middle frequencies (12 & 16 kHz), initial thresholds were just under 20 dB SPL and increased until they became different from initial at 16-18 months. At 24 kHz, initial thresholds were just above 20 dB and became different from initial at 13-16 months of age. The rate of change of thresholds with age were similar for all frequencies until about 30 months of age, when 32 kHz threshold changes lagged behind other frequencies. Generally, CBA/CaJ mice in our colony display relatively low thresholds until approximately 16 months of age, depending on frequency. After 16-18 months, thresholds become significantly worse. After approximately 20-22 months thresholds increase linearly with age.

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.