Auditory Neurophysiology publications

The auditory midbrain implant (AMI) consists of a single shank array (20 sites) for stimulation along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) and has been safely implanted in deaf patients who cannot benefit from a cochlear implant (CI). The AMI improves lip-reading abilities and environmental awareness in the implanted patients. However, the AMI cannot achieve the high levels of speech perception possible with the CI. It appears the AMI can transmit sufficient spectral cues but with limited temporal cues required for speech understanding. Currently, the AMI uses a CI-based strategy, which was originally designed to stimulate each frequency region along the cochlea with amplitude-modulated pulse trains matching the envelope of the bandpass-filtered sound components. However, it is unclear if this type of stimulation with only a single site within each frequency lamina of the ICC can elicit sufficient temporal cues for speech perception. At least speech understanding in quiet is still possible with envelope cues as low as 50 Hz. Therefore, we investigated how ICC neurons follow the bandpass-filtered envelope structure of natural stimuli in ketamine-anesthetized guinea pigs. We identified a subset of ICC neurons that could closely follow the envelope structure (up to ~100 Hz) of a diverse set of species-specific calls, which was revealed by using a peripheral ear model to estimate the true bandpass-filtered envelopes observed by the brain. Although previous studies have suggested a complex neural transformation from the auditory nerve to the ICC, our data suggest that the brain maintains a robust temporal code in a subset of ICC neurons matching the envelope structure of natural stimuli. Clinically, these findings suggest that a CI-based strategy may still be effective for the AMI if the appropriate neurons are entrained to the envelope of the acoustic stimulus and can transmit sufficient temporal cues to higher centers.

Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs "silently" in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period.

Key points The cerebral cortex plays a critical role in perception and in learning‐induced plasticity. We show that reversibly silencing any of the main regions of auditory cortex impairs the ability of adult ferrets to localize sound, with the largest deficit seen after deactivating the primary fields. Although these animals had no trouble localizing longer sound bursts, their performance dropped considerably when auditory spatial cues were altered by occluding one ear with an earplug. In contrast to control ferrets, which recovered their localization abilities with intensive training, adaptation to an earplug was impaired following cortical inactivation, with the greatest disruption in plasticity observed after silencing higher‐level cortical areas. These findings imply regional differences in the processing of spatial information across the auditory cortex. Abstract The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABA A agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol‐Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach‐to‐target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach‐to‐target responses to brief sounds (40 ms noise bursts) was reduced by muscimol‐Elvax but not by drug‐free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience‐induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach‐to‐target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher‐level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex.

Background In a natural environment, contextual noise frequently occurs with a signal sound for detection or discrimination in a temporal relation. However, the representation of sound frequency by auditory cortical neurons in a noisy environment is not fully understood. Therefore, the purpose of this study was to explore the impact of contextual noise on the cortical tuning to signal sound frequency in order to better understand the mechanism of cortical frequency coding in a complex acoustical environment. Results We compared the excitatory frequency-level receptive fields (FLRFs) of neurons in the rat primary auditory cortex determined under both quiet and preceding noise conditions. Based on the changes of minimum threshold and the extent of FLRF of auditory cortical neurons, we found that the FLRFs of a cortical neuron were modulated dynamically by a varying preceding noise. When the interstimulus interval between noise and the probe tone was constant, the modulation of the FLRF increased as the level of noise was increased. If the preceding noise level was constant, the modulation decreased when the interstimulus interval was increased. Preceding noise sharpened the bandwidth of the FLRFs of 47.6% tested neurons. Moreover, preceding noise shifted the CFs of 47.6% neurons by more than 0.25 octaves, while the CFs of the rest of the neurons remained relatively unchanged. Conclusions The results indicate that the cortical representation of sound frequency is dynamically modulated by contextual acoustical environment, and that there are cortical neurons whose characteristic frequencies were resistant to the interference of contextual noise.

To date, the functional and physiological impact on the mature brain of moderate-level environmental noises that do not cause noticeable peripheral deficits remains largely unstudied. Here we show that exposing adult rats to structured noise at a sound pressure level of 65 dB, which is markedly below the broadly accepted safety level standard, results in behavioural impairments and substantially impairs the function of the auditory cortex. The strong deterioration in cortical processing of acoustic inputs is independent of the modulation rates of structured noises. Almost equally strong effects result from 10-h daily versus 24-h daily exposure regimens. These results indicate that there can be substantial negative consequences for the auditory system documented at the cortical level, attributable to environmental exposure to structured noises delivered under conditions that do not directly impact hearing sensitivity. These noises are deemed to be 'safe' and are often present in modern human environments.

Studies on the maturation of auditory motion processing in children have yielded inconsistent reports. The present study combines subjective and objective measurements to investigate how the auditory perceptual abilities of children change during development and whether these changes are paralleled by changes in the event-related brain potential (ERP). We employed the mismatch negativity (MMN) to determine maturational changes in the discrimination of interaural time differences (ITDs) that generate lateralized moving auditory percepts. MMNs were elicited in children, teenagers, and adults, using a small and a large ITD at stimulus offset with respect to each subject's discrimination threshold. In adults and teenagers large deviants elicited prominent MMNs, whereas small deviants at the behavioral threshold elicited only a marginal or no MMN. In contrast, pronounced MMNs for both deviant sizes were found in children. Behaviorally, however, most of the children showed higher discrimination thresholds than teens and adults. Although automatic ITD detection is functional, active discrimination is still limited in children. The lack of MMN deviance dependency in children suggests that unlike in teenagers and adults, neural signatures of automatic auditory motion processing do not mirror discrimination abilities. The study critically accounts for advanced understanding of children's central auditory development.

Background: Sound production and hearing sensitivity of ectothermic animals are affected by the ambient temperature. This is the first study investigating the influence of temperature on both sound production and on hearing abilities in a fish species, namely the neotropical Striped Raphael catfish Platydoras armatulus. Methodology/principal findings: Doradid catfishes produce stridulation sounds by rubbing the pectoral spines in the shoulder girdle and drumming sounds by an elastic spring mechanism which vibrates the swimbladder. Eight fish were acclimated for at least three weeks to 22°, then to 30° and again to 22°C. Sounds were recorded in distress situations when fish were hand-held. The stridulation sounds became shorter at the higher temperature, whereas pulse number, maximum pulse period and sound pressure level did not change with temperature. The dominant frequency increased when the temperature was raised to 30°C and the minimum pulse period became longer when the temperature decreased again. The fundamental frequency of drumming sounds increased at the higher temperature. Using the auditory evoked potential (AEP) recording technique, the hearing thresholds were tested at six different frequencies from 0.1 to 4 kHz. The temporal resolution was determined by analyzing the minimum resolvable click period (0.3-5 ms). The hearing sensitivity was higher at the higher temperature and differences were more pronounced at higher frequencies. In general, latencies of AEPs in response to single clicks became shorter at the higher temperature, whereas temporal resolution in response to double-clicks did not change. Conclusions/significance: These data indicate that sound characteristics as well as hearing abilities are affected by temperatures in fishes. Constraints imposed on hearing sensitivity at different temperatures cannot be compensated even by longer acclimation periods. These changes in sound production and detection suggest that acoustic orientation and communication are affected by temperature changes in the neotropical catfish P. armatulus.

Animal experiments suggest that chronic tinnitus ("ringing in the ears") may result from processes that overcompensate for lost afferent input. Abnormally elevated spontaneous neural activity has been found in the dorsal cochlear nucleus (DCN) of animals with psychophysical evidence of tinnitus. However, it has also been reported that DCN ablation fails to reduce established tinnitus. Since other auditory areas have been implicated in tinnitus, the role of the DCN is unresolved. The apparently conflicting electrophysiological and lesion data can be reconciled if the DCN serves as a necessary trigger zone rather than a chronic generator of tinnitus. The present experiment used lesion procedures identical to those that failed to decrease pre-existing tinnitus. The exception was that lesions were done prior to tinnitus induction. Young adult rats were trained and tested using a psychophysical procedure shown to detect tinnitus. Tinnitus was induced by a single unilateral high-level noise exposure. Consistent with the trigger hypothesis, bilateral dorsal DCN lesions made before high-level noise exposure prevented the development of tinnitus. A protective effect stemming from disruption of the afferent pathway could not explain the outcome because unilateral lesions ipsilateral to the noise exposure did not prevent tinnitus and unilateral lesions contralateral to the noise exposure actually exacerbated the tinnitus. The DCN trigger mechanism may involve plastic circuits that, through loss of inhibition, or upregulation of excitation, increase spontaneous neural output to rostral areas such as the inferior colliculus. The increased drive could produce persistent pathological changes in the rostral areas, such as high-frequency bursting and decreased interspike variance, that comprise the chronic tinnitus signal.

Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners.

We have previously shown that neurons in primary auditory cortex (A1) of anaesthetized (ketamine/medetomidine) ferrets respond more strongly and reliably to dynamic stimuli whose statistics follow "natural" 1/f dynamics than to stimuli exhibiting pitch and amplitude modulations that are faster (1/f(0.5)) or slower (1/f(2)) than 1/f. To investigate where along the central auditory pathway this 1/f-modulation tuning arises, we have now characterized responses of neurons in the central nucleus of the inferior colliculus (ICC) and the ventral division of the mediate geniculate nucleus of the thalamus (MGV) to 1/f(γ) distributed stimuli with γ varying between 0.5 and 2.8. We found that, while the great majority of neurons recorded from the ICC showed a strong preference for the most rapidly varying (1/f(0.5) distributed) stimuli, responses from MGV neurons did not exhibit marked or systematic preferences for any particular γ exponent. Only in A1 did a majority of neurons respond with higher firing rates to stimuli in which γ takes values near 1. These results indicate that 1/f tuning emerges at forebrain levels of the ascending auditory pathway.

Acoustic communication has an important role in the reproductive behaviour of anurans. Although males of the concave-eared frog (Odorrana tormota) have shown an ultrasonic communication capacity adapted to the intense, predominately low-frequency ambient noise from local streams, whether the females communicate with ultrasound remains unclear. Here we present evidence that females exhibit no ultrasonic sensitivity. Acoustic playback experiments show that the calls from male evoke phonotaxis and vocal responses from gravid females, whereas the ultrasonic components (frequencies above 20 kHz) of the calls do not elicit any phonotaxis or vocalization in the females. Electrophysiological recordings from the auditory midbrain reveal an upper frequency limit at 16 kHz in females. Laser Doppler vibrometer measurements show that the velocity amplitude of the tympanic membranes peaks at 5 kHz in females and at ∼7 kHz in males. The auditory sex differences in O. tormota imply that ultrasonic hearing has evolved only in male anurans.

The auditory system must represent sounds with a wide range of statistical properties. One important property is the spectrotemporal contrast in the acoustic environment: the variation in sound pressure in each frequency band, relative to the mean pressure. We show that neurons in ferret auditory cortex rescale their gain to partially compensate for the spectrotemporal contrast of recent stimulation. When contrast is low, neurons increase their gain, becoming more sensitive to small changes in the stimulus, although the effectiveness of contrast gain control is reduced at low mean levels. Gain is primarily determined by contrast near each neuron's preferred frequency, but there is also a contribution from contrast in more distant frequency bands. Neural responses are modulated by contrast over timescales of ∼100 ms. By using contrast gain control to expand or compress the representation of its inputs, the auditory system may be seeking an efficient coding of natural sounds.

Background: The weberian apparatus of otophysine fishes facilitates sound transmission from the swimbladder to the inner ear to increase hearing sensitivity. It has been of great interest to biologists since the 19(th) century. No studies, however, are available on the development of the weberian ossicles and its effect on the development of hearing in catfishes. Methodology/principal findings: We investigated the development of the weberian apparatus and auditory sensitivity in the catfish Lophiobagrus cyclurus. Specimens from 11.3 mm to 85.5 mm in standard length were studied. Morphology was assessed using sectioning, histology, and X-ray computed tomography, along with 3D reconstruction. Hearing thresholds were measured utilizing the auditory evoked potentials recording technique. Weberian ossicles and interossicular ligaments were fully developed in all stages investigated except in the smallest size group. In the smallest catfish, the intercalarium and the interossicular ligaments were still missing and the tripus was not yet fully developed. Smallest juveniles revealed lowest auditory sensitivity and were unable to detect frequencies higher than 2 or 3 kHz; sensitivity increased in larger specimens by up to 40 dB, and frequency detection up to 6 kHz. In the size groups capable of perceiving frequencies up to 6 kHz, larger individuals had better hearing abilities at low frequencies (0.05-2 kHz), whereas smaller individuals showed better hearing at the highest frequencies (4-6 kHz). Conclusions/significance: Our data indicate that the ability of otophysine fish to detect sounds at low levels and high frequencies largely depends on the development of the weberian apparatus. A significant increase in auditory sensitivity was observed as soon as all weberian ossicles and interossicular ligaments are present and the chain for transmitting sounds from the swimbladder to the inner ear is complete. This contrasts with findings in another otophysine, the zebrafish, where no threshold changes have been observed.

Although an object-based account of auditory attention has become an increasingly popular model for understanding how temporally overlapping sounds are segregated, relatively little is known about the cortical circuit that supports such ability. In the present study, we applied a beamformer spatial filter to magnetoencephalography (MEG) data recorded during an auditory paradigm that used inharmonicity to promote the formation of multiple auditory objects. Using this unconstrained, data-driven approach, the evoked field component linked with the perception of multiple auditory objects (i.e., the object-related negativity; ORNm), was found to be associated with bilateral auditory cortex sources that were distinct from those coinciding with the P1m, N1m, and P2m responses elicited by sound onset. The right hemispheric ORNm source in particular was consistently positioned anterior to the other sources across two experiments. These findings are consistent with earlier proposals of multiple auditory object detection being associated with generators in the auditory cortex and further suggest that these neural populations are distinct from the long latency evoked responses reflecting the detection of sound onset.

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex.

Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other subcortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20-24°C among cells within a radius of about 2.5 mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C) but this was not sufficient to directly reduce neural activity. In an effort to visualize the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

Many fishes rely on their auditory skills to interpret crucial information about predators and prey, and to communicate intraspecifically. Few studies, however, have examined how complex natural sounds are perceived in fishes. We investigated the representation of conspecific mating and agonistic calls in the auditory system of the Lusitanian toadfish Halobatrachus didactylus , and analysed auditory responses to heterospecific signals from ecologically relevant species: a sympatric vocal fish (meagre Argyrosomus regius ) and a potential predator (dolphin Tursiops truncatus ). Using auditory evoked potential (AEP) recordings, we showed that both sexes can resolve fine features of conspecific calls. The toadfish auditory system was most sensitive to frequencies well represented in the conspecific vocalizations (namely the mating boatwhistle), and revealed a fine representation of duration and pulsed structure of agonistic and mating calls. Stimuli and corresponding AEP amplitudes were highly correlated, indicating an accurate encoding of amplitude modulation. Moreover, Lusitanian toadfish were able to detect T. truncatus foraging sounds and A. regius calls, although at higher amplitudes. We provide strong evidence that the auditory system of a vocal fish, lacking accessory hearing structures, is capable of resolving fine features of complex vocalizations that are probably important for intraspecific communication and other relevant stimuli from the auditory scene.

Cave fish have rarely been investigated with regard to their inner ear morphology, hearing abilities, and acoustic communication. Based on a previous study that revealed morphological differences in the saccular otolith between a cave and two surface populations of Poecilia mexicana, we checked for additional differences in utricular and lagenar otoliths and tested whether different populations have similar hearing sensitivities. We found pronounced differences in the shape of all three otoliths. Otoliths of the saccule and lagena from cave fish differed from those of surface fish in the features of the face oriented towards the sensory epithelium. In addition, otoliths of the utricle and lagena were significantly heavier in cave fish. Auditory sensitivities were measured between 100 and 1500Hz, utilizing the auditory evoked potential recording technique. We found similar hearing abilities in cave and surface fish, with greatest sensitivity between 200 and 300Hz. An acoustic survey revealed that neither ecotype produced species-specific sounds. Our data indicate that cave dwelling altered the otolith morphology in Atlantic mollies, probably due to metabolic differences. Different otolith morphology, however, did not affect general auditory sensitivity or acoustic behavior.

Sensory systems are known to adapt their coding strategies to the statistics of their environment, but little is still known about the perceptual implications of such adjustments. We investigated how auditory spatial processing adapts to stimulus statistics by presenting human listeners and anesthetized ferrets with noise sequences in which interaural level differences (ILD) rapidly fluctuated according to a Gaussian distribution. The mean of the distribution biased the perceived laterality of a subsequent stimulus, whereas the distribution's variance changed the listeners' spatial sensitivity. The responses of neurons in the inferior colliculus changed in line with these perceptual phenomena. Their ILD preference adjusted to match the stimulus distribution mean, resulting in large shifts in rate-ILD functions, while their gain adapted to the stimulus variance, producing pronounced changes in neural sensitivity. Our findings suggest that processing of auditory space is geared toward emphasizing relative spatial differences rather than the accurate representation of absolute position.