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Sinusoidal amplitude modulation (SAM) is a key feature of complex sounds. While psychophysical studies have characterized SAM perception, and neurophysiological studies in anesthetized animals report a transformation from the cochlear nucleus' (CN; brainstem) temporal code to the inferior colliculus' (IC; midbrain's) rate code, none have used awake animals or nonhuman primates to compare CN and IC's coding strategies to modulation-frequency perception. To address this, we recorded single-unit responses and compared derived neurometric measures in the CN and IC to psychometric measures of modulation frequency (MF) discrimination in macaques. IC and CN neurons often exhibited tuned responses to SAM in rate and spike-timing measures of modulation coding. Neurometric thresholds spanned a large range (2-200 Hz DMF). The lowest 40% of IC thresholds were less than or equal to psychometric thresholds, regardless of which code was used, while CN thresholds were greater than psychometric thresholds. Discrimination at 10-20 Hz could be explained by indiscriminately pooling 30 units in either structure, while discrimination at higher MFs was best explained by more selective pooling. This suggests that pooled CN activity was sufficient for AM discrimination. Psychometric and neurometric thresholds decreased as stimulus duration increased, but IC and CN thresholds were higher and more variable than behavior at short durations. This slower subcortical temporal integration compared to behavior was consistent with a drift diffusion model which reproduced individual differences in performance and can constrain future neurophysiological studies of temporal integration. These measures provide an account of AM perception at the neurophysiological, computational, and behavioral levels.
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Detection of sounds is a fundamental function of the auditory system. Although studies of auditory cortex have gained substantial insight into detection performance using behaving animals, previous subcortical studies have mostly taken place under anesthesia, in passively listening animals, or have not measured performance at threshold. These limitations preclude direct comparisons between neuronal responses and behavior. To address this, we simultaneously measured auditory detection performance and single-unit activity in the inferior colliculus (IC) and cochlear nucleus (CN) in macaques. The spontaneous activity and response variability of CN neurons were higher than those observed for IC neurons. Signal detection theoretic methods revealed that the magnitude of responses of IC neurons provided more reliable estimates of psychometric threshold and slope compared with the responses of single CN neurons. However, pooling small populations of CN neurons provided reliable estimates of psychometric threshold and slope, suggesting sufficient information in CN population activity. Trial-by-trial correlations between spike count and behavioral response emerged 50-75 ms after sound onset for most IC neurons, but for few neurons in the CN. These results highlight hierarchical differences between neurometric-psychometric correlations in CN and IC and have important implications for how subcortical information could be decoded.NEW & NOTEWORTHY The cerebral cortex is widely recognized to play a role in sensory processing and decision-making. Accounts of the neural basis of auditory perception and its dysfunction are based on this idea. However, significantly less attention has been paid to midbrain and brainstem structures in this regard. Here, we find that subcortical auditory neurons represent stimulus information sufficient for detection and predict behavioral choice on a trial-by-trial basis.
Assuntos
Córtex Auditivo , Núcleo Coclear , Colículos Inferiores , Animais , Colículos Inferiores/fisiologia , Percepção Auditiva/fisiologia , Córtex Auditivo/fisiologia , Núcleo Coclear/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Vias Auditivas/fisiologiaRESUMO
The human dopamine (DA) transporter (hDAT) mediates clearance of DA. Genetic variants in hDAT have been associated with DA dysfunction, a complication associated with several brain disorders, including autism spectrum disorder (ASD). Here, we investigated the structural and behavioral bases of an ASD-associated in-frame deletion in hDAT at N336 (∆N336). We uncovered that the deletion promoted a previously unobserved conformation of the intracellular gate of the transporter, likely representing the rate-limiting step of the transport process. It is defined by a "half-open and inward-facing" state (HOIF) of the intracellular gate that is stabilized by a network of interactions conserved phylogenetically, as we demonstrated in hDAT by Rosetta molecular modeling and fine-grained simulations, as well as in its bacterial homolog leucine transporter by electron paramagnetic resonance analysis and X-ray crystallography. The stabilization of the HOIF state is associated both with DA dysfunctions demonstrated in isolated brains of Drosophila melanogaster expressing hDAT ∆N336 and with abnormal behaviors observed at high-time resolution. These flies display increased fear, impaired social interactions, and locomotion traits we associate with DA dysfunction and the HOIF state. Together, our results describe how a genetic variation causes DA dysfunction and abnormal behaviors by stabilizing a HOIF state of the transporter.
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Transtorno do Espectro Autista/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Dopamina/genética , Locomoção/genética , Animais , Animais Geneticamente Modificados , Transtorno do Espectro Autista/fisiopatologia , Cristalografia por Raios X , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Espectroscopia de Ressonância de Spin Eletrônica , Medo/fisiologia , Humanos , Relações Interpessoais , Locomoção/fisiologia , Modelos Moleculares , Mutação , Deleção de Sequência/genéticaRESUMO
The relationship between sound duration and detection threshold has long been thought to reflect temporal integration. Reports of species differences in this relationship are equivocal: some meta-analyses report no species differences, whereas others report substantial differences, particularly between humans and their close phylogenetic relatives, macaques. This renders translational work in macaques problematic. To reevaluate this difference, tone detection performance was measured in macaques using a go/no-go reaction time (RT) task at various tone durations and in the presence of broadband noise (BBN). Detection thresholds, RTs, and the dynamic range (DR) of the psychometric function decreased as the tone duration increased. The threshold by duration trends suggest macaques integrate at a similar rate to humans. The RT trends also resemble human data and are the first reported in animals. Whereas the BBN did not affect how the threshold or RT changed with the duration, it substantially reduced the DR at short durations. A probabilistic Poisson model replicated the effects of duration on threshold and DR and required integration from multiple simulated auditory nerve fibers to explain the performance at shorter durations. These data suggest that, contrary to previous studies, macaques are uniquely well-suited to model human temporal integration and form the baseline for future neurophysiological studies.
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Benchmarking , Macaca , Animais , Limiar Auditivo , Humanos , Filogenia , SomRESUMO
Auditory neuronal responses are modified by background noise. Inferior colliculus (IC) neuronal responses adapt to the most frequent sound level within an acoustic scene (adaptation to stimulus statistics), a mechanism that may preserve neuronal and behavioral thresholds for signal detection. However, it is still unclear whether the presence of foreground stimuli and/or task involvement can modify neuronal adaptation. To investigate how task engagement interacts with this mechanism, we compared the response of IC neurons to background noise, which caused adaptation to stimulus statistics, while macaque monkeys performed a masked tone detection task (task-driven condition) with responses recorded when the same background noise was presented alone (passive listening condition). In the task-dependent condition, monkeys performed a Go/No-Go task while 50-ms tones were embedded within an adaptation-inducing continuous background noise whose levels changed every 50 ms and were drawn from a probability distribution. The adaptation to noise stimulus statistics in IC neuronal responses was significantly enhanced in the task-driven condition compared with the passive listening condition, showing that foreground stimuli and/or task-engagement can modify IC neuronal responses. Additionally, the response of IC neurons to noise was significantly affected by the preceding sensory information (history effect) regardless of task involvement. These studies show that dynamic range adaptation in IC preserves behavioral and neurometric thresholds irrespective of noise type and a dependence of neuronal activity on task-related factors at subcortical levels of processing.NEW & NOTEWORTHY Auditory neuronal responses are influenced by maskers and distractors. However, it is still unclear whether the neuronal sensitivity to the masker stimulus is influenced by task-dependent factors. Our study represents one of the first attempts to investigate how task involvement influences the neural representation of background sounds in the subcortical, midbrain auditory neurons of behaving animals.
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Adaptação Fisiológica , Percepção Auditiva/fisiologia , Colículos Inferiores/fisiologia , Neurônios/fisiologia , Desempenho Psicomotor , Estimulação Acústica , Animais , Macaca mulatta , Macaca radiataRESUMO
Exposure to prolonged or high intensity noise increases the risk for permanent hearing impairment. Over several decades, researchers characterized the nature of harmful noise exposures and worked to establish guidelines for effective protection. Recent laboratory studies, primarily conducted in rodent models, indicate that the auditory system may be more vulnerable to noise-induced hearing loss (NIHL) than previously thought, driving renewed inquiries into the harmful effects of noise in humans. To bridge the translational gaps between rodents and humans, nonhuman primates (NHPs) may serve as key animal models. The phylogenetic proximity of NHPs to humans underlies tremendous similarity in many features of the auditory system (genomic, anatomical, physiological, behavioral), all of which are important considerations in the assessment and treatment of NIHL. This review summarizes the literature pertaining to NHPs as models of hearing and noise-induced hearing loss, discusses factors relevant to the translation of diagnostics and therapeutics from animals to humans, and concludes with some of the practical considerations involved in conducting NHP research.
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Modelos Animais de Doenças , Perda Auditiva Provocada por Ruído/fisiopatologia , Primatas/fisiologia , Animais , Perda Auditiva Provocada por Ruído/patologia , Perda Auditiva Provocada por Ruído/terapia , Humanos , Psicoacústica , Pesquisa Translacional BiomédicaRESUMO
The detectability of target sounds embedded within noisy backgrounds is affected by the regularities that summarize acoustic sceneries. Previous studies suggested that the dynamic range of neurons in the inferior colliculus (IC) of anesthetized guinea pigs shifts toward the mean sound pressure level in irregular acoustic environments. Yet, it is unclear how this neuronal adaptation processes may influence the effectiveness of sounds as a masker, both behaviorally and in terms of neuronal encoding. To answer this question, we measured the neural response of IC neurons while macaque monkeys performed a Go/No-Go tone detection task. Macaques detected a 50-ms tone that was either simultaneously gated with a burst of noise or embedded within a continuous noise background, whose levels were randomly sampled (every 50 ms) from a probability distribution. The mean of the distribution matched the level of the gated burst of noise. Psychometric and IC neurometric thresholds to tones did not differ between the two masking conditions. However, the neuronal firing rate versus level function was significantly affected by the temporal characteristics of the noise masker. Simultaneously gated noise caused higher baseline responses and greater dynamic range compression compared with noise distribution. The slopes of psychometric and neurometric functions were significantly shallower for higher variance distributions, suggesting that neuronal sensitivity might change with the variability of the sound. Our results suggest that the adaptive response of IC neurons to sound regularities does not affect the effectiveness of the noise-masking signal, which remains invariant to surrounding noise amplitudes. NEW & NOTEWORTHY Auditory neurons adapt to the statistics of sound levels in the acoustic scene. However, it is still unclear to what extent such adaptation influences the effectiveness of the stimulus as a masker. Our study represents the first attempt to investigate how the adaptation to the statistics of masking stimuli may be related to the effectiveness of masking, and to the single-unit encoding of the midbrain auditory neurons in behaving animals.
Assuntos
Adaptação Fisiológica , Colículos Inferiores/fisiologia , Neurônios/fisiologia , Mascaramento Perceptivo , Percepção da Altura Sonora , Animais , Colículos Inferiores/citologia , Macaca mulatta , Masculino , Modelos Neurológicos , Limiar SensorialRESUMO
Acoustic noise and other environmental variables represent potential confounds for animal research. Of relevance to auditory research, sustained high levels of ambient noise may modify hearing sensitivity and decrease well-being among laboratory animals. The present study was conducted to assess environmental conditions in an animal facility that houses nonhuman primates used for auditory research at the Vanderbilt University Medical Center. Sound levels, vibration, temperature, humidity and luminance were recorded using an environmental monitoring device placed inside of an empty cage in a macaque housing room. Recordings lasted 1 week each, at three different locations within the room. Vibration, temperature, humidity and luminance all varied within recommended levels for nonhuman primates, with one exception of low luminance levels in the bottom cage location. Sound levels at each cage location were characterized by a low baseline of 58-62 dB sound pressure level, with transient peaks up to 109 dB sound pressure level. Sound levels differed significantly across locations, but only by about 1.5 dB. The transient peaks beyond recommended sound levels reflected a very low noise dose, but exceeded startle-inducing levels, which could elicit stress responses. Based on these findings, ambient noise levels in the housing rooms in this primate facility are within acceptable levels and unlikely to contribute to hearing deficits in the nonhuman primates. Our results establish normative values for environmental conditions in a primate facility, can be used to inform best practices for nonhuman primate research and care, and form a baseline for future studies of aging and chronic noise exposure.
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Animais de Laboratório , Ruído , Animais , Animais de Laboratório/fisiologia , Audição/fisiologia , Abrigo para Animais , Humanos , Ruído/efeitos adversos , VibraçãoRESUMO
The middle-ear system relies on a balance of mass and stiffness characteristics for transmitting sound from the external environment to the cochlea and auditory neural pathway. Phase is one aspect of sound that, when transmitted and encoded by both ears, contributes to binaural cue sensitivity and spatial hearing. The study aims were (i) to investigate the effects of middle-ear stiffness on the auditory brainstem neural encoding of phase in human adults with normal pure-tone thresholds and (ii) to investigate the relationships between middle-ear stiffness-induced changes in wideband acoustic immittance and neural encoding of phase. The auditory brainstem neural encoding of phase was measured using the auditory steady-state response (ASSR) with and without middle-ear stiffness elicited via contralateral activation of the middle-ear muscle reflex (MEMR). Middle-ear stiffness was quantified using a wideband acoustic immittance assay of acoustic absorbance. Statistical analyses demonstrated decreased ASSR phase lag and decreased acoustic absorbance with contralateral activation of the MEMR, consistent with increased middle-ear stiffness changing the auditory brainstem neural encoding of phase. There were no statistically significant correlations between stiffness-induced changes in wideband acoustic absorbance and ASSR phase. The findings of this study may have important implications for understanding binaural cue sensitivity and horizontal plane sound localization in audiologic and otologic clinical populations that demonstrate changes in middle-ear stiffness, including cochlear implant recipients who use combined electric and binaural acoustic hearing and otosclerosis patients.
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Orelha Média , Testes Auditivos , Adulto , Humanos , Orelha Média/fisiologia , Testes Auditivos/métodos , Audição , Nervo Coclear , Tronco Encefálico , Limiar Auditivo/fisiologia , Estimulação AcústicaRESUMO
Clinical auditory physiological measures (e.g., auditory brainstem responses, ABRs, and distortion product otoacoustic emissions, DPOAEs) provide diagnostic specificity for differentially diagnosing overt hearing impairments, but they remain limited in their ability to detect specific sites of lesion and subtle levels of cochlear damage. Studies in animal models may hold the key to improve differential diagnosis due to the ability to induce tightly controlled and histologically verifiable subclinical cochlear pathologies. Here, we present a normative set of traditional and clinically novel physiological measures using ABRs and DPOAEs measured in a large cohort of male macaque monkeys. Given the high similarities between macaque and human auditory anatomy, physiology, and susceptibility to hearing damage, this normative data set will serve as a crucial baseline to investigate novel physiological measures to improve diagnostics. DPOAE amplitudes were robust at f2 = 1.22, L1/L2 = 65/55, increased with frequency up to 10 kHz, and exhibited high test re-test reliability. DPOAE thresholds were lowest from 2-10 kHz and highest < 2 kHz. ABRs with a standard clinical electrode montage (vertex-to-mastoid, VM) produced Waves I-IV with a less frequently observed Wave-I, and lower thresholds. ABRs with a vertex-to-tympanic membrane (VT) electrode montage produced a more robust Wave-I, but absent Waves II-IV and higher thresholds. Further study with the VM montage revealed amplitudes that increased with stimulus level and were largest in response to click stimuli, with Wave-II showing the largest ABR amplitude, followed by -IV and -I, with high inter- and intra-subject variability. ABR wave latencies decreased with stimulus level and frequency. When stimulus presentation rate increased or stimuli were presented in close temporal proximity, ABR amplitude decreased, and latency increased. These findings expand upon existing literature of normative clinical physiological data in nonhuman primates and lay the groundwork for future studies investigating the effects of noise-induced pathologies in macaques.
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Macaca , Emissões Otoacústicas Espontâneas , Animais , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Haplorrinos , Humanos , Masculino , Emissões Otoacústicas Espontâneas/fisiologia , Reprodutibilidade dos TestesRESUMO
Otitis externa (OE) is a condition that involves inflammation of the external ear canal. OE is a commonly reported condition in humans and some veterinary species (for example, dogs, cats), but has not been reported in the literature in macaques. Here, we present a case series of acute and chronic OE likely precipitated by abrasion of the ear canal with a tympanic membrane electrode in 7 adult male rhesus macaques (Macaca mulatta). All animals displayed purulent, mucinous discharge from 1 or both ears with 3 macaques also displaying signs of an upper respiratory tract (URT) infection during the same period. A variety of diagnostic and treatment options were pursued including consultation with an otolaryngologist necessitated by the differences in response to treatment in macaques as compared with other common veterinary species. Due to the nature of the studies in which these macaques were enrolled, standard audiological testing was performed before and after OE, including tympanometry, auditory brainstem responses (ABRs), and distortion product otoacoustic emissions (DPOAEs). After completion of study procedures, relevant tissues were collected for necropsy and histopathology. Impaired hearing was found in all macaques even after apparent resolution of OE signs. Necropsy findings included abnormalities in the tympanic membrane, ossicular chain, and middle ear cavity, suggesting that the hearing impairment was at least partly conductive in nature. We concluded that OE likely resulted from mechanical disruption of the epithelial lining of the ear canal by the ABR electrode, thereby allowing the development of opportunistic infections. OE, while uncommon in macaques, can affect them and should be included as a differential diagnosis of any macaque presenting with otic discharge and/or auricular discomfort.
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Macaca mulatta , Otite Externa , Animais , Meato Acústico Externo , Eletrodos/efeitos adversos , Masculino , Otite Externa/epidemiologia , Otite Externa/etiologia , Otite Externa/veterinária , Membrana TimpânicaRESUMO
In the psychophysical phenomenon visual bias, an accurately localized irrelevant signal, such as a light, impairs localization of a spatially discrepant target, such as a sound, when the two stimuli are perceived as unified. Many studies have demonstrated visual bias in azimuth, but none have tested directly or found this effect in depth. The current study was able to produce over 90% bias in azimuth and somewhat less (83%) bias in depth. A maximum likelihood estimate can predict bias by the variance in the localization of each unimodal signal in each dimension in space.
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Atenção/fisiologia , Percepção de Profundidade/fisiologia , Mascaramento Perceptivo/fisiologia , Localização de Som/fisiologia , Percepção Espacial/fisiologia , Adolescente , Adulto , Viés , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Adulto JovemRESUMO
In a naturalistic environment, auditory cues are often accompanied by information from other senses, which can be redundant with or complementary to the auditory information. Although the multisensory interactions derived from this combination of information and that shape auditory function are seen across all sensory modalities, our greatest body of knowledge to date centers on how vision influences audition. In this review, we attempt to capture the state of our understanding at this point in time regarding this topic. Following a general introduction, the review is divided into 5 sections. In the first section, we review the psychophysical evidence in humans regarding vision's influence in audition, making the distinction between vision's ability to enhance versus alter auditory performance and perception. Three examples are then described that serve to highlight vision's ability to modulate auditory processes: spatial ventriloquism, cross-modal dynamic capture, and the McGurk effect. The final part of this section discusses models that have been built based on available psychophysical data and that seek to provide greater mechanistic insights into how vision can impact audition. The second section reviews the extant neuroimaging and far-field imaging work on this topic, with a strong emphasis on the roles of feedforward and feedback processes, on imaging insights into the causal nature of audiovisual interactions, and on the limitations of current imaging-based approaches. These limitations point to a greater need for machine-learning-based decoding approaches toward understanding how auditory representations are shaped by vision. The third section reviews the wealth of neuroanatomical and neurophysiological data from animal models that highlights audiovisual interactions at the neuronal and circuit level in both subcortical and cortical structures. It also speaks to the functional significance of audiovisual interactions for two critically important facets of auditory perception-scene analysis and communication. The fourth section presents current evidence for alterations in audiovisual processes in three clinical conditions: autism, schizophrenia, and sensorineural hearing loss. These changes in audiovisual interactions are postulated to have cascading effects on higher-order domains of dysfunction in these conditions. The final section highlights ongoing work seeking to leverage our knowledge of audiovisual interactions to develop better remediation approaches to these sensory-based disorders, founded in concepts of perceptual plasticity in which vision has been shown to have the capacity to facilitate auditory learning.
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Percepção Auditiva , Percepção Visual , Estimulação Acústica , Animais , Audição , Humanos , Estimulação LuminosaRESUMO
The binaural interaction component (BIC) is a sound-evoked electrophysiological signature of binaural processing in the auditory brainstem that has received attention as a potential biomarker for spatial hearing deficits. Yet the number of trials necessary to evoke the BIC, or its measurability, seems to vary across species: while it is easily measured in small rodents, it has proven to be highly variable and less reliably measured in humans. This has hindered its potential use as a diagnostic tool. Further measurements of the BIC across a wide range of species could help us better understand its origin and the possible reasons for the variation in its measurability. Statistical analysis on the function relating BIC DN1 amplitude and the interaural time difference has been performed in only a few small rodent species, thus it remains to be shown how the results apply to more taxonomically diverse mammals, and those with larger heads. To fill this gap, we measured BICs in rhesus macaque. We show the overall behavior of the BIC is the same as in smaller rodents, suggesting that the brainstem circuit responsible for the BIC is conserved across a wider range of mammals. We suggest that differences in measurability are likely because of differences in head size.
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Tronco Encefálico , Potenciais Evocados Auditivos do Tronco Encefálico , Estimulação Acústica , Animais , Macaca mulatta , SomRESUMO
Noise-induced hearing loss (NIHL) is known to have significant consequences for temporal, spectral, and spatial resolution. However, much remains to be discovered about their underlying pathophysiology. This report extends the recent development of a nonhuman primate model of NIHL to explore its consequences for hearing in noisy environments, and its correlations with the underlying cochlear pathology. Ten macaques (seven with normal-hearing, three with NIHL) were used in studies of masked tone detection in which the temporal or spatial properties of the masker were varied to assess metrics of temporal and spatial processing. Normal-hearing (NH) macaques showed lower tone detection thresholds for sinusoidally amplitude modulated (SAM) broadband noise maskers relative to unmodulated maskers (modulation masking release, MMR). Tone detection thresholds were lowest at low noise modulation frequencies, and increased as modulation frequency increased, until they matched threshold in unmodulated noise. NH macaques also showed lower tone detection thresholds for spatially separated tone and noise relative to co-localized tone and noise (spatial release from masking, SRM). Noise exposure caused permanent threshold shifts that were verified behaviorally and audiologically. In hearing-impaired (HI) macaques, MMR was reduced at tone frequencies above that of the noise exposure. HI macaques also showed degraded SRM, with no SRM observed across all tested tone frequencies. Deficits in MMR correlated with audiometric threshold changes, outer hair cell loss, and synapse loss, while the differences in SRM did not correlate with audiometric changes, or any measure of cochlear pathophysiology. This difference in anatomical-behavioral correlations suggests that while many behavioral deficits may arise from cochlear pathology, only some are predictable from the frequency place of damage in the cochlea.
Assuntos
Perda Auditiva Provocada por Ruído , Processamento Espacial , Animais , Limiar Auditivo , Cóclea , Perda Auditiva Provocada por Ruído/etiologia , Macaca , Ruído/efeitos adversos , Mascaramento PerceptivoRESUMO
There is now a good deal of data from neurophysiological studies in animals and behavioral studies in human infants regarding the development of multisensory processing capabilities. Although the conclusions drawn from these different datasets sometimes appear to conflict, many of the differences are due to the use of different terms to mean the same thing and, more problematic, the use of similar terms to mean different things. Semantic issues are pervasive in the field and complicate communication among groups using different methods to study similar issues. Achieving clarity of communication among different investigative groups is essential for each to make full use of the findings of others, and an important step in this direction is to identify areas of semantic confusion. In this way investigators can be encouraged to use terms whose meaning and underlying assumptions are unambiguous because they are commonly accepted. Although this issue is of obvious importance to the large and very rapidly growing number of researchers working on multisensory processes, it is perhaps even more important to the non-cognoscenti. Those who wish to benefit from the scholarship in this field but are unfamiliar with the issues identified here are most likely to be confused by semantic inconsistencies. The current discussion attempts to document some of the more problematic of these, begin a discussion about the nature of the confusion and suggest some possible solutions.
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Neurologia/normas , Sensação/fisiologia , Terminologia como Assunto , Estimulação Acústica , Animais , Humanos , Lactente , Recém-Nascido , Neurologia/métodos , Estimulação Luminosa , SemânticaRESUMO
Noise-induced hearing loss (NIHL) has been well investigated across diverse mammalian species and the potential for prevention of NIHL is of broad interest. To most efficiently develop novel therapeutic interventions, a good understanding of the current state of knowledge regarding mechanisms of injury is essential. The overarching goals of this review are to 1) concisely summarize the current state of knowledge, and 2) provide opinions on the most significant future trends and developments.
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Exposure to loud noise causes damage to the inner ear, including but not limited to outer and inner hair cells (OHCs and IHCs) and IHC ribbon synapses. This cochlear damage impairs auditory processing and increases audiometric thresholds (noise-induced hearing loss, NIHL). However, the exact relationship between the perceptual consequences of NIHL and its underlying cochlear pathology are poorly understood. This study used a nonhuman primate model of NIHL to relate changes in frequency selectivity and audiometric thresholds to indices of cochlear histopathology. Three macaques (one Macaca mulatta and two Macaca radiata) were trained to detect tones in quiet and in noises that were spectrally notched around the tone frequency. Audiograms were derived from tone thresholds in quiet; perceptual auditory filters were derived from tone thresholds in notched-noise maskers using the rounded-exponential fit. Data were obtained before and after a four-hour exposure to a 50-Hz noise centered at 2 kHz at 141 or 146 dB SPL. Noise exposure caused permanent audiometric threshold shifts and broadening of auditory filters at and above 2 kHz, with greater changes observed for the 146-dB-exposed monkeys. The normalized bandwidth of the perceptual auditory filters was strongly correlated with audiometric threshold at each tone frequency. While changes in audiometric threshold and perceptual auditory filter widths were primarily determined by the extent of OHC survival, additional variability was explained by including interactions among OHC, IHC, and ribbon synapse survival. This is the first study to provide within-subject comparisons of auditory filter bandwidths in an animal model of NIHL and correlate these NIHL-related perceptual changes with cochlear histopathology. These results expand the foundations for ongoing investigations of the neural correlates of NIHL-related perceptual changes.
Assuntos
Perda Auditiva Provocada por Ruído , Animais , Limiar Auditivo , Cóclea , Perda Auditiva Provocada por Ruído/etiologia , MacacaRESUMO
Single-neuron studies provide a foundation for understanding many facets of multisensory integration. These studies have used a variety of criteria for identifying and quantifying multisensory integration. While a number of techniques have been used, an explicit discussion of the assumptions, criteria, and analytical methods traditionally used to define the principles of multisensory integration is lacking. This was not problematic when the field was small, but with rapid growth a number of alternative techniques and models have been introduced, each with its own criteria and sets of implicit assumptions to define and characterize what is thought to be the same phenomenon. The potential for misconception prompted this reexamination of traditional approaches in order to clarify their underlying assumptions and analytic techniques. The objective here is to review and discuss traditional quantitative methods advanced in the study of single-neuron physiology in order to appreciate the process of multisensory integration and its impact.
Assuntos
Pesquisa Biomédica/métodos , Encéfalo/fisiologia , Neurônios/fisiologia , Percepção/fisiologia , Animais , Modelos Neurológicos , Dinâmica não Linear , Projetos de Pesquisa , Colículos Superiores/fisiologiaRESUMO
The auditory system is thought to process complex sounds through overlapping bandpass filters. Frequency selectivity as estimated by auditory filters has been well quantified in humans and other mammalian species using behavioral and physiological methodologies, but little work has been done to examine frequency selectivity in nonhuman primates. In particular, knowledge of macaque frequency selectivity would help address the recent controversy over the sharpness of cochlear tuning in humans relative to other animal species. The purpose of our study was to investigate the frequency selectivity of macaque monkeys using a notched-noise paradigm. Four macaques were trained to detect tones in noises that were spectrally notched symmetrically and asymmetrically around the tone frequency. Masked tone thresholds decreased with increasing notch width. Auditory filter shapes were estimated using a rounded exponential function. Macaque auditory filters were symmetric at low noise levels and broader and more asymmetric at higher noise levels with broader low-frequency and steeper high-frequency tails. Macaque filter bandwidths (BW3dB) increased with increasing center frequency, similar to humans and other species. Estimates of equivalent rectangular bandwidth (ERB) and filter quality factor (QERB) suggest macaque filters are broader than human filters. These data shed further light on frequency selectivity across species and serve as a baseline for studies of neuronal frequency selectivity and frequency selectivity in subjects with hearing loss.