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Hearing Research Mar 2024Hearing loss affects approximately 18% of the population worldwide. Hearing difficulties in noisy environments without accompanying audiometric threshold shifts likely... (Review)
Review
Hearing loss affects approximately 18% of the population worldwide. Hearing difficulties in noisy environments without accompanying audiometric threshold shifts likely affect an even larger percentage of the global population. One of the potential causes of hidden hearing loss is cochlear synaptopathy, the loss of synapses between inner hair cells (IHC) and auditory nerve fibers (ANF). These synapses are the most vulnerable structures in the cochlea to noise exposure or aging. The loss of synapses causes auditory deafferentation, i.e., the loss of auditory afferent information, whose downstream effect is the loss of information that is sent to higher-order auditory processing stages. Understanding the physiological and perceptual effects of this early auditory deafferentation might inform interventions to prevent later, more severe hearing loss. In the past decade, a large body of work has been devoted to better understand hidden hearing loss, including the causes of hidden hearing loss, their corresponding impact on the auditory pathway, and the use of auditory physiological measures for clinical diagnosis of auditory deafferentation. This review synthesizes the findings from studies in humans and animals to answer some of the key questions in the field, and it points to gaps in knowledge that warrant more investigation. Specifically, recent studies suggest that some electrophysiological measures have the potential to function as indicators of hidden hearing loss in humans, but more research is needed for these measures to be included as part of a clinical test battery.
Topics: Animals; Humans; Hearing Loss, Noise-Induced; Noise; Auditory Threshold; Hearing Loss, Hidden; Auditory Perception; Cochlea; Synapses; Evoked Potentials, Auditory, Brain Stem
PubMed: 38335624
DOI: 10.1016/j.heares.2024.108967 -
Iranian Journal of Basic Medical... 2024Aging causes progressive degenerative changes in many organs, particularly the auditory system. Several attempts have been conducted to investigate preventive and... (Review)
Review
Aging causes progressive degenerative changes in many organs, particularly the auditory system. Several attempts have been conducted to investigate preventive and therapeutic strategy/strategies for age-related auditory dysfunction, such as maintaining a healthy lifestyle through good nutrition, lower anxiety levels, and noise exposure, different pharmacological approaches, gene and cell therapy, and other strategies. However, it is not clear which approach is the best to slow down these dysfunctions because several different underlying mechanistic pathways are associated with presbycusis which eventually leads to different types of this disease. A combination of several methods is probably required, whereas the effectiveness for some people needs to be monitored. The effectiveness of treatments will not be the same for all; therefore, we may need to have a unique and personalized approach to the prevention and treatment of ARHL for each person. In addition, each method needs to specify what type of presbycusis can prevent or treat and provide complete information about the extent, duration of treatment, persistency of treatment, side effects, and whether the approach is for treatment or prevention or even both. This paper reviews the updated literature, which targets current interventions for age-related hearing loss.
PubMed: 38333758
DOI: 10.22038/IJBMS.2023.72863.15849 -
Nature Chemistry Mar 2024The human enzyme p97 regulates various cellular pathways by unfolding hundreds of protein substrates in an ATP-dependent manner, making it an essential component of...
The human enzyme p97 regulates various cellular pathways by unfolding hundreds of protein substrates in an ATP-dependent manner, making it an essential component of protein homeostasis and an impactful pharmacological target. The hexameric complex undergoes substantial conformational changes throughout its catalytic cycle. Here we elucidate the molecular motions that occur at the active site in the temporal window immediately before and after ATP hydrolysis by merging cryo-EM, NMR spectroscopy and molecular dynamics simulations. p97 populates a metastable reaction intermediate, the ADP·P state, which is poised between hydrolysis and product release. Detailed snapshots reveal that the active site is finely tuned to trap and eventually discharge the cleaved phosphate. Signalling pathways originating at the active site coordinate the action of the hexamer subunits and couple hydrolysis with allosteric conformational changes. Our multidisciplinary approach enables a glimpse into the sophisticated spatial and temporal orchestration of ATP handling by a prototype AAA+ protein.
Topics: Humans; Adenosine Triphosphate; Adenosine Triphosphatases; Valosin Containing Protein; Molecular Dynamics Simulation
PubMed: 38326645
DOI: 10.1038/s41557-024-01440-0 -
PLoS Biology Feb 2024Effective interactions with the environment rely on the integration of multisensory signals: Our brains must efficiently combine signals that share a common source, and...
Effective interactions with the environment rely on the integration of multisensory signals: Our brains must efficiently combine signals that share a common source, and segregate those that do not. Healthy ageing can change or impair this process. This functional magnetic resonance imaging study assessed the neural mechanisms underlying age differences in the integration of auditory and visual spatial cues. Participants were presented with synchronous audiovisual signals at various degrees of spatial disparity and indicated their perceived sound location. Behaviourally, older adults were able to maintain localisation accuracy. At the neural level, they integrated auditory and visual cues into spatial representations along dorsal auditory and visual processing pathways similarly to their younger counterparts but showed greater activations in a widespread system of frontal, temporal, and parietal areas. According to multivariate Bayesian decoding, these areas encoded critical stimulus information beyond that which was encoded in the brain areas commonly activated by both groups. Surprisingly, however, the boost in information provided by these areas with age-related activation increases was comparable across the 2 age groups. This dissociation-between comparable information encoded in brain activation patterns across the 2 age groups, but age-related increases in regional blood-oxygen-level-dependent responses-contradicts the widespread notion that older adults recruit new regions as a compensatory mechanism to encode task-relevant information. Instead, our findings suggest that activation increases in older adults reflect nonspecific or modulatory mechanisms related to less efficient or slower processing, or greater demands on attentional resources.
Topics: Humans; Aged; Bayes Theorem; Brain Mapping; Visual Perception; Brain; Attention; Acoustic Stimulation; Auditory Perception; Photic Stimulation; Magnetic Resonance Imaging
PubMed: 38319934
DOI: 10.1371/journal.pbio.3002494 -
Research Square Jan 2024Recent failures translating preclinical behavioral treatment effects to positive clinical trial results in humans with Fragile X Syndrome (FXS) support refocusing...
Recent failures translating preclinical behavioral treatment effects to positive clinical trial results in humans with Fragile X Syndrome (FXS) support refocusing attention on biological pathways and associated measures, such as electroencephalography (EEG), with strong translational potential and small molecule target engagement. This study utilized guided machine learning to test promising translational EEG measures (resting power and auditory chirp oscillatory variables) in a large heterogeneous sample of individuals with FXS to identify best performing EEG variables for reliably separating individuals with FXS, and genetically-mediated subgroups within FXS, from typically developing controls. Best performing variables included resting relative frontal theta power, all combined whole-head resting power bands, posterior peak alpha frequency (PAF), combined PAF across all measured regions, combined theta, alpha, and gamma power during the chirp, and all combined chirp oscillatory variables. Sub-group analyses best discriminated non-mosaic FXS males via whole-head resting relative power (AUC = .9250), even with data reduced to a 20-channel clinical montage. FXS females were nearly perfectly discriminated by combined theta, alpha, and gamma power during the chirp (AUC = .9522). Results support use of resting and auditory oscillatory tasks to reliably identify neural deficit in FXS, and to identify specific translational targets for genetically-mediated sub-groups, supporting potential points for stratification.
PubMed: 38313274
DOI: 10.21203/rs.3.rs-3849272/v1 -
BioRxiv : the Preprint Server For... Jan 2024The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well-suited for accurate analysis of...
The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well-suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that restrict MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ('wedge-slice'). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The 'in vivo-like' timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hyper-suppression of cochlear activity.
PubMed: 38313270
DOI: 10.1101/2023.12.21.572886 -
Hearing Research Mar 2024Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections...
Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL.
Topics: Humans; Rats; Animals; Hearing Loss, Noise-Induced; Inferior Colliculi; Noise; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Cochlea
PubMed: 38308936
DOI: 10.1016/j.heares.2024.108963 -
Frontiers in Psychology 2023Congenital toxoplasmosis (CT) occurs mainly by primary maternal infection during pregnancy. It is estimated that the incidence of vertical transmission to the fetus is...
BACKGROUND
Congenital toxoplasmosis (CT) occurs mainly by primary maternal infection during pregnancy. It is estimated that the incidence of vertical transmission to the fetus is 20% and that infected women are more likely to have a premature birth or low birth weight neonate since there is an association between CT and the rate of premature birth and low birth weight. In addition to severe neurological and ophthalmic consequences, hearing disorders such as hearing loss are also among the clinical manifestations seen in children with CT. Given the above, the objective of this study is to verify what are the auditory disorders seen in children with CT.
METHODS
This literature review was structured according to the PRISMA statement and based on the terms of Study Target Population, Intervention, Comparison, Outcomes, and Study Types (PICOS). To obtain the studies, the following electronic databases were consulted: PubMed, Web of Science, Scopus, and Lilacs. The combined terms used for the search were: ("auditory evoked potentials" OR "hearing" OR "hearing loss") AND ("congenital toxoplasmosis"). The selection of articles was carried out independently, blindly, by two of the authors, to minimize risk of bias.
RESULTS
The search in the databases identified 172 articles, after excluding duplicate articles, 105 studies were identified. From the selection made by reading the titles and abstracts, 11 studies were selected for full-text reading. A total of 94 studies were excluded. An article was selected from the list of references. Therefore, 12 studies were included in the final analysis. It was observed that a significant percentage of studies sought to study the peripheral auditory pathway, verifying the occurrence or association between hearing loss and the presence of congenital infection. Only two studies evaluated the central auditory pathway, using the Brainstem Auditory Evoked Potential (BAEP) and the Frequency Following Response (FFR).
CONCLUSION
Toxoplasmosis affects not only the peripheral areas but central areas as well. Most studies suggest this pathology as a risk factor for both peripheral and central impairment. Research has found a greater association between CT and mild to moderate hearing loss, in addition to alterations in exams such as BAEP and FFR. These data recommend that CT be reported as a global public health problem and can help assess complications and impacts of hearing disorders as a result of CT. There is a gap about studies that retract the co-occurrence between CT and other Risk Indicators for Hearing Loss (RIHL), such as prematurity, permanence in the intensive care unit, and use of ototoxic medications, lack of longitudinal studies, that accompany the development of hearing and language of children with CT, since the consequences of this infection may be late.
PubMed: 38298366
DOI: 10.3389/fpsyg.2023.1286211 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jan 2024Nicotinamide adenine dinucleotide(NADH) in its reduced form of is a key coenzyme in redox reactions, essential for maintaining energy homeostasis.NADH and its... (Review)
Review
Nicotinamide adenine dinucleotide(NADH) in its reduced form of is a key coenzyme in redox reactions, essential for maintaining energy homeostasis.NADH and its oxidized counterpart, NAD+, form a redox couple that regulates various biological processes, including calcium homeostasis, synaptic plasticity, anti-apoptosis, and gene expression. The reduction of NAD+/NADH levels is closely linked to mitochondrial dysfunction, which plays a pivotal role in the cascade of various neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease.Auditory neuropathy(AN) is recognized as a clinical biomarker in neurodegenerative disorders. Furthermore, mitochondrial dysfunction has been identified in patients with mutations in genes like and . However, effective treatments for these conditions are still lacking. Increasing evidence suggests that administratering NAD+ or its precursors endogenously may potentially prevent and slow disease progression by enhancing DNA repair and improving mitochondrial function. Therefore, this review concentrates on the metabolic pathways of NAD+/NADH production and their biological functions, and delves into the therapeutic potential and mechanisms of NADH in treating AN.
Topics: Humans; NAD; Neurodegenerative Diseases; Mitochondria; Oxidation-Reduction; Mitochondrial Diseases
PubMed: 38297850
DOI: 10.13201/j.issn.2096-7993.2024.01.009 -
Current Biology : CB Feb 2024Many motor control systems generate multiple movements using a common set of muscles. How are premotor circuits able to flexibly generate diverse movement patterns?...
Many motor control systems generate multiple movements using a common set of muscles. How are premotor circuits able to flexibly generate diverse movement patterns? Here, we characterize the neuronal circuits that drive the distinct courtship songs of Drosophila melanogaster. Male flies vibrate their wings toward females to produce two different song modes-pulse and sine song-which signal species identity and male quality. Using cell-type-specific genetic reagents and the connectome, we provide a cellular and synaptic map of the circuits in the male ventral nerve cord that generate these songs and examine how activating or inhibiting each cell type within these circuits affects the song. Our data reveal that the song circuit is organized into two nested feedforward pathways with extensive reciprocal and feedback connections. The larger network produces pulse song, the more complex and ancestral song form. A subset of this network produces sine song, the simpler and more recent form. Such nested organization may be a common feature of motor control circuits in which evolution has layered increasing flexibility onto a basic movement pattern.
Topics: Animals; Female; Male; Drosophila; Drosophila melanogaster; Courtship; Sexual Behavior, Animal; Neurons
PubMed: 38295797
DOI: 10.1016/j.cub.2024.01.015