Mammalian behavior and physiology converge to confirm sharper cochlear tuning in humans

Frequency analysis of sound by the cochlea is the most fundamental property of the auditory system. Despite its importance, the resolution of this frequency analysis in humans remains controversial. The controversy persists because the methods used to estimate tuning in humans are indirect and have not all been independently validated in other species. Some data suggest that human cochlear tuning is considerably sharper than that of laboratory animals, while others suggest little or no difference between species. We show here in a single species (ferret) that behavioral estimates of tuning bandwidths obtained using perceptual masking methods, and objective estimates obtained using otoacoustic emissions, both also employed in humans, agree closely with direct physiological measurements from single auditory-nerve fibers. Combined with human behavioral data, this outcome indicates that the frequency analysis performed by the human cochlea is of significantly higher resolution than found in common laboratory animals. This finding raises important questions about the evolutionary origins of human cochlear tuning, its role in the emergence of speech communication, and the mechanisms underlying our ability to separate and process natural sounds in complex acoustic environments

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Speech Perception in Tones and Noise via Cochlear Implants Reveals Influence of Spectral Resolution on Temporal Processing

Under normal conditions, human speech is remarkably robust to degradation by noise and other distortions. However, people with hearing loss, including those with cochlear implants, often experience great difficulty in understanding speech in noisy environments. Recent work with normal-hearing listeners has shown that the amplitude fluctuations inherent in noise contribute strongly to the masking of speech. In contrast, this study shows that speech perception via a cochlear implant is unaffected by the inherent temporal fluctuations of noise. This qualitative difference between acoustic and electric auditory perception does not seem to be due to differences in underlying temporal acuity but can instead be explained by the poorer spectral resolution of cochlear implants, relative to the normally functioning ear, which leads to an effective smoothing of the inherent temporal-envelope fluctuations of noise. The outcome suggests an unexpected trade-off between the detrimental effects of poorer spectral resolution and the beneficial effects of a smoother noise temporal envelope. This trade-off provides an explanation for the long-standing puzzle of why strong correlations between speech understanding and spectral resolution have remained elusive. The results also provide a potential explanation for why cochlear-implant users and hearing-impaired listeners exhibit reduced or absent masking release when large and relatively slow temporal fluctuations are introduced in noise maskers. The multitone maskers used here may provide an effective new diagnostic tool for assessing functional hearing loss and reduced spectral resolution

Data from: Auditory enhancement under forward masking in normal-hearing and hearing-impaired listeners

Two files are included: ReadMe.txt (general layout of the data in the Excel Workbook) and DRUM_HIENH.xls (Excel document with 40 sheets that contain individual data for each participant and condition). The archival copy of the DRUM_HIENH file is a zip folder containing .csv, .txt., and .html files of the relevant data, formulas, and formatting in the excel document.A target within a spectrally notched masker can be enhanced by a preceding copy of the masker. Enhancement can also increase the effectiveness of the target as a forward masker. Enhancement has been reported in hearing-impaired listeners under simultaneous but not forward masking. However, previous studies of enhancement under forward masking did not fully assess the potential effect of differences in sensation level or spectral resolution between the normal-hearing and hearing-impaired listeners. This study measured enhancement via forward masking in hearing-impaired and age-matched normal-hearing listeners with different spectral notches in the masker, to account for potential differences in frequency selectivity, and with levels equated by adding a background masking noise to equate both sensation level and sound pressure level or by reducing the sound pressure level of the stimuli to equate sensation level.NIH NIDCD Grant R01 DC 01226

Modulation rate discrimination using half-wave rectified and sinusoidally amplitude modulated stimuli in cochlear-implant users

Detection and modulation rate discrimination were measured in cochlear-implant users for pulse-trains that were either sinusoidally amplitude modulated or were modulated with half-wave rectified sinusoids, which in acoustic hearing have been used to simulate the response to low-frequency temporal fine structure. In contrast to comparable results from acoustic hearing, modulation rate discrimination was not statistically different for the two stimulus types. The results suggest that, in contrast to binaural perception, pitch perception in cochlear-implant users does not benefit from using stimuli designed to more closely simulate the cochlear response to low-frequency pure tones

A Fast Method for Measuring Psychophysical Thresholds Across the Cochlear Implant Array

A rapid threshold measurement procedure, based on Bekesy tracking, is proposed and evaluated for use with cochlear implants (CIs). Fifteen postlingually deafened adult CI users participated. Absolute thresholds for 200-ms trains of biphasic pulses were measured using the new tracking procedure and were compared with thresholds obtained with a traditional forced-choice adaptive procedure under both monopolar and quadrupolar stimulation. Virtual spectral sweeps across the electrode array were implemented in the tracking procedure via current steering, which divides the current between two adjacent electrodes and varies the proportion of current directed to each electrode. Overall, no systematic differences were found between threshold estimates with the new channel sweep procedure and estimates using the adaptive forced-choice procedure. Test–retest reliability for the thresholds from the sweep procedure was somewhat poorer than for thresholds from the forced-choice procedure. However, the new method was about 4 times faster for the same number of repetitions. Overall the reliability and speed of the new tracking procedure provides it with the potential to estimate thresholds in a clinical setting. Rapid methods for estimating thresholds could be of particular clinical importance in combination with focused stimulation techniques that result in larger threshold variations between electrodes

Comparing Rapid and Traditional Forward-Masked Spatial Tuning Curves in Cochlear-Implant Users

A rapid forward-masked spatial tuning curve measurement procedure, based on Bekesy tracking, was adapted and evaluated for use with cochlear implants. Twelve postlingually-deafened adult cochlear-implant users participated. Spatial tuning curves using the new procedure and using a traditional forced-choice adaptive procedure resulted in similar estimates of parameters. The Bekesy-tracking method was almost 3 times faster than the forced-choice procedure, but its test–retest reliability was significantly poorer. Although too time-consuming for general clinical use, the new method may have some benefits in individual cases, where identifying electrodes with poor spatial selectivity as candidates for deactivation is deemed necessary