Comparing the electrophysiological effects of traumatic noise exposure between rodents.

Noise-induced hearing deficits are important health problems in the industrialized world. As the underlying physiological dysfunctions are not well understood, research in suitable animal models is urgently needed. Three rodent species (Mongolian gerbil, rat, and mouse) were studied to compare the temporal dynamics of noise-induced hearing loss after identical procedures of noise exposure. Auditory brainstem responses (ABRs) were measured before, during, and up to 8 wk after noise exposure for threshold determination and ABR waveform analysis. Trauma induction with stepwise increasing sound pressure level was interrupted by five interspersed ABR measurements. Comparing short- and long-term dynamics underlying the following noise-induced hearing loss revealed diverging time courses between the three species. Hearing loss occurred early on during noise exposure in all three rodent species at or above trauma frequency. Initial noise level (105 dB SPL) was most effective in rats whereas the delayed level increase to 115 dB SPL affected mice much stronger. Induced temporary threshold shifts in rats and mice were larger in animals with lower pretrauma ABR thresholds. The increase in activity (gain) along the auditory pathway was derived by comparing the amplitudes of short- and long-latency ABR waveform components. Directly after trauma, significant effects were found for rats (decreasing gain) and mice (increasing gain) whereas gerbils revealed high individual variability in gain changes. Taken together, our comparative study revealed pronounced species-specific differences in the development of noise-induced hearing loss and the related processing along the auditory pathway.NEW & NOTEWORTHY We compared deficits after noise trauma in different rodents that are typically used in hearing research (Mongolian gerbil, rat, and mouse). We observed noise-induced threshold changes and alterations in the activity of processing auditory information along the ascending auditory pathway. Our results reveal pronounced differences in the characteristics of trauma-induced damage in these different rodent groups.

Dependence of the Startle Response on Temporal and Spectral Characteristics of Acoustic Modulatory Influences in Rats and Gerbils.

The acoustic startle response (ASR) and its modulation by non-startling prepulses, presented shortly before the startle-eliciting stimulus, is a broadly applied test paradigm to determine changes in neural processing related to auditory or psychiatric disorders. Modulation by a gap in background noise as a prepulse is especially used for tinnitus assessment. However, the timing and frequency-related aspects of prepulses are not fully understood. The present study aims to investigate temporal and spectral characteristics of acoustic stimuli that modulate the ASR in rats and gerbils. For noise-burst prepulses, inhibition was frequency-independent in gerbils in the test range between 4 and 18 kHz. Prepulse inhibition (PPI) by noise-bursts in rats was constant in a comparable range (8-22 kHz), but lower outside this range. Purely temporal aspects of prepulse-startle-interactions were investigated for gap-prepulses focusing mainly on gap duration. While very short gaps had no (rats) or slightly facilitatory (gerbils) influence on the ASR, longer gaps always had a strong inhibitory effect. Inhibition increased with durations up to 75 ms and remained at a high level of inhibition for durations up to 1000 ms for both, rats and gerbils. Determining spectral influences on gap-prepulse inhibition (gap-PPI) revealed that gerbils were unaffected in the limited frequency range tested (4-18 kHz). The more detailed analysis in rats revealed a variety of frequency-dependent effects. Gaps in pure-tone background elicited constant and high inhibition (around 75%) over a broad frequency range (4-32 kHz). For gaps in noise-bands, on the other hand, a clear frequency-dependency was found: inhibition was around 50% at lower frequencies (6-14 kHz) and around 70% at high frequencies (16-20 kHz). This pattern of frequency-dependency in rats was specifically resulting from the inhibitory effect by the gaps, as revealed by detailed analysis of the underlying startle amplitudes. An interaction of temporal and spectral influences, finally, resulted in higher inhibition for 500 ms gaps than for 75 ms gaps at all frequencies tested. Improved prepulse paradigms based on these results are well suited to quantify the consequences of central processing disorders.

Stimulus-specific adaptation in field potentials and neuronal responses to frequency-modulated tones in the primary auditory cortex.

In order to structure the sensory environment our brain needs to detect changes in the surrounding that might indicate events of presumed behavioral relevance. A characteristic brain response presumably related to the detection of such novel stimuli is termed mismatch negativity (MMN) observable in human scalp recordings. A candidate mechanism underlying MMN at the neuronal level is stimulus-specific adaptation (SSA) which has several characteristics in common. SSA is the specific decrease in the response to a frequent stimulus, which does not generalize to an interleaved rare stimulus in a sequence of events. SSA was so far mainly described for changes in the response to simple pure tone stimuli differing in tone frequency. In this study we provide data from the awake rat auditory cortex on adaptation in the responses to frequency-modulated tones (FM) with the deviating feature being the direction of FM modulation. Adaptation of cortical neurons to the direction of FM modulation was stronger for slow modulation than for faster modulation. In contrast to pure tone SSA which showed no stimulus preference, FM adaptation in neuronal data differed sometimes between upward and downward FM. This, however, was not the case in the local field potential data recorded simultaneously. Our findings support the role of the auditory cortex as the source for change-related activity induced by FM stimuli by showing that dynamic stimulus features such as FM modulation can evoke SSA in the rat in a way very similar to FM-induced MMN in the human auditory cortex.

Representation of frequency-modulated sounds in the human brain.

Frequency-modulation is a ubiquitous sound feature present in communicative sounds of various animal species and humans. Functional imaging of the human auditory system has seen remarkable advances in the last two decades and studies pertaining to frequency-modulation have centered around two major questions: a) are there dedicated feature-detectors encoding frequency-modulation in the brain and b) is there concurrent representation with amplitude-modulation, another temporal sound feature? In this review, we first describe how these two questions are motivated by psychophysical studies and neurophysiology in animal models. We then review how human non-invasive neuroimaging studies have furthered our understanding of the representation of frequency-modulated sounds in the brain. Finally, we conclude with some suggestions on how human neuroimaging could be used in future studies to address currently still open questions on this fundamental sound feature. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Characterization of the perceived sound of trauma-induced tinnitus in gerbils.

Tinnitus often develops following inner ear pathologies, like acoustic trauma. Therefore, an acoustic trauma model of tinnitus in gerbils was established using a modulated acoustic startle response. Cochlear trauma evoked by exposure to narrow-band noise at 10 kHz was assessed by auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). Threshold shift amounted to about 25 dB at frequencies > 10 kHz. Induction of a phantom-noise perception was documented by an acoustic startle response paradigm. A reduction of the gap-prepulse inhibition of acoustic startle (GPIAS) was taken as evidence for tinnitus at the behavioral level. Three to five weeks after trauma the ABR and DPOAE thresholds were back to normal. At that time, a reduction of GPIAS in the frequency range 16-20 kHz indicated a phantom noise perception. Seven weeks post trauma the tinnitus-affected frequency range became narrow and shifted to the center-trauma frequency at 10 kHz. Taken together, by investigating frequency-dependent effects in detail, this study in gerbils found trauma-evoked tinnitus developing in the frequency range bordering the low frequency slope of the induced noise trauma. This supports the theory of lateral inhibition as the physiological basis of tinnitus.

Repetition of complex frequency-modulated sweeps enhances neuromagnetic responses in the human auditory cortex.

Frequency modulations (FM) play a decisive role in our everyday communication. To investigate the processing of FM direction we measured change-related auditory cortex responses with human magnetoencephalography. First, we tested for FM direction selectivity by presenting FM sweeps with the same FM directions in a repeated series (RS). These series were interrupted by a deviant with the opposite FM direction. Second, we tested for the representation of abstract rules and presented series of FM sweeps with alternating FM directions (AS). The AS series were interrupted by a deviant which was a repetition of the series' last FM sweep but broke the alternating pattern. For the RS, the deviant did not evoke significant change-related responses in the auditory cortex. However, for the first stimulus after the deviant, significantly stronger responses compared to standards were observed bilaterally in the auditory cortex at about 200 ms after stimulus onset. For the AS, we observed a similar bilateral change-related signal enhancement for a deviant FM sweep breaking the alternating series. Since this response enhancement occurred for both RS and AS even after a single FM sweep repetition, we conclude that these activities represent local signal enhancements rather than change-related responses due to abstract rule violation. In sum, our data indicate repetition enhancement due to spectro-temporal interactions between successive complex FM sweeps. These enhancement effects were observed for the first but not further repetitions suggesting a second-order repetition suppression of the initial repetition enhancement.

Stimulus-specific adaptation in the gerbil primary auditory thalamus is the result of a fast frequency-specific habituation and is regulated by the corticofugal system.

The detection of novel and therefore potentially behavioral relevant stimuli is of fundamental importance for animals. In the auditory system, stimulus-specific adaptation (SSA) resulting in stronger responses to rare compared with frequent stimuli was proposed as such a novelty detection mechanism. SSA is a now well established phenomenon found at different levels along the mammalian auditory pathway. It depends on various stimulus features, such as deviant probability, and may be an essential mechanism underlying perception of changes in sound statistics. We recorded neuronal responses from the ventral part of the medial geniculate body (vMGB) in Mongolian gerbils to determine details of the adaptation process that might indicate underlying neuronal mechanisms. Neurons in the vMGB exhibited a median spike rate change of 15.4% attributable to a fast habituation to the frequently presented standard stimulus. Accordingly, the main habituation effect could also be induced by the repetition of a few uniform tonal stimuli. The degree of habituation was frequency-specific, and comparison across simultaneously recorded units indicated that adaptation effects were apparently topographically organized. At the population level, stronger habituation effects were on average associated with the border regions of the frequency response areas. Finally, the pharmacological inactivation of the auditory cortex demonstrated that SSA in the vMGB is mainly regulated by the corticofugal system. Hence, these results indicate a more general function of SSA in the processing and analysis of auditory information than the term novelty detection suggests.

Seed-dispersal distributions by trumpeter hornbills in fragmented landscapes.

Frugivorous birds provide important ecosystem services by transporting seeds of fleshy fruited plants. It has been assumed that seed-dispersal kernels generated by these animals are generally leptokurtic, resulting in little dispersal among habitat fragments. However, little is known about the seed-dispersal distribution generated by large frugivorous birds in fragmented landscapes. We investigated movement and seed-dispersal patterns of trumpeter hornbills (Bycanistes bucinator) in a fragmented landscape in South Africa. Novel GPS loggers provide high-quality location data without bias against recording long-distance movements. We found a very weakly bimodal seed-dispersal distribution with potential dispersal distances up to 14.5 km. Within forest, the seed-dispersal distribution was unimodal with an expected dispersal distance of 86 m. In the fragmented agricultural landscape, the distribution was strongly bimodal with peaks at 18 and 512 m. Our results demonstrate that seed-dispersal distributions differed when birds moved in different habitat types. Seed-dispersal distances in fragmented landscapes show that transport among habitat patches is more frequent than previously assumed, allowing plants to disperse among habitat patches and to track the changing climatic conditions.

Repetition enhancement for frequency-modulated but not unmodulated sounds: a human MEG study.

BACKGROUND: Decoding of frequency-modulated (FM) sounds is essential for phoneme identification. This study investigates selectivity to FM direction in the human auditory system. METHODOLOGY/PRINCIPAL FINDINGS: Magnetoencephalography was recorded in 10 adults during a two-tone adaptation paradigm with a 200-ms interstimulus-interval. Stimuli were pairs of either same or different frequency modulation direction. To control that FM repetition effects cannot be accounted for by their on- and offset properties, we additionally assessed responses to pairs of unmodulated tones with either same or different frequency composition. For the FM sweeps, N1m event-related magnetic field components were found at 103 and 130 ms after onset of the first (S1) and second stimulus (S2), respectively. This was followed by a sustained component starting at about 200 ms after S2. The sustained response was significantly stronger for stimulation with the same compared to different FM direction. This effect was not observed for the non-modulated control stimuli. CONCLUSIONS/SIGNIFICANCE: Low-level processing of FM sounds was characterized by repetition enhancement to stimulus pairs with same versus different FM directions. This effect was FM-specific; it did not occur for unmodulated tones. The present findings may reflect specific interactions between frequency separation and temporal distance in the processing of consecutive FM sweeps.

Correlating stimulus-specific adaptation of cortical neurons and local field potentials in the awake rat.

Changes in the sensory environment are good indicators for behaviorally relevant events and strong triggers for the reallocation of attention. In the auditory domain, violations of a pattern of repetitive stimuli precipitate in the event-related potentials as mismatch negativity (MMN). Stimulus-specific adaptation (SSA) of single neurons in the auditory cortex has been proposed to be the cellular substrate of MMN (Nelken and Ulanovsky, 2007). However, until now, the existence of SSA in the awake auditory cortex has not been shown. In the present study, we recorded single and multiunits in parallel with evoked local field potentials (eLFPs) in the primary auditory cortex of the awake rat. Both neurons and eLFPs in the awake animal adapted in a stimulus-specific manner, and SSA was controlled by stimulus probability and frequency separation. SSA of isolated units was significant during the first stimulus-evoked "on" response but not in the following inhibition and rebound of activity. The eLFPs exhibited SSA in the first negative deflection and, to a lesser degree, in a slower positive deflection but no MMN. Spike adaptation correlated closely with adaptation of the fast negative deflection but not the positive deflection. Therefore, we conclude that single neurons in the auditory cortex of the awake rat adapt in a stimulus-specific manner and contribute to corresponding changes in eLFP but do not generate a late deviant response component directly equivalent to the human MMN. Nevertheless, the described effect may reflect a certain part of the process needed for sound discrimination.

Acoustic startle and prepulse inhibition in the Mongolian gerbil.

The acoustic startle response has been studied in great detail in rodents, however almost only in rats and mice, two very similar, domesticated animals. The Mongolian gerbil (Meriones unguiculatus) is an established animal model for auditory research with good low-frequency hearing that covers most of the human audiogram. Gerbils have also been used to investigate the influence of domestication on auditory-related behavior. We characterized the acoustic startle response in gerbils and determined the influence of domestication by directly comparing animals from a domesticated with a wild-type strain. Mongolian gerbils showed a strong and reliable acoustic startle response to noise bursts above a threshold of 77-80 dB SPL which levels out above 115 dB SPL. Only domesticated gerbils showed short-term habituation to repetitive stimulation while the responses in wild-type animals remained at about the same level. Prepulse inhibition of the acoustic startle response by noise burst or gap-in-noise prepulses in gerbils was strong, maximum prepulse inhibition induced by noise bursts was between 67% (wild-types) and 90% (domesticated). Differences between domesticated and wild-type gerbils were even more pronounced for gap-prepulse inhibition. For a gap duration of 50 ms with a lead time of 100 ms, percent inhibition in domesticated gerbils (80%) was almost double the inhibition in wild-types. Such strong prepulse inhibition can be very useful as a basis for efficient audiometric measurements in gerbils.

Influence of contralateral acoustic stimulation on the quadratic distortion product f2-f1 in humans.

Contralateral acoustic stimulation is known to activate the medial olivocochlear system which is capable of modulating the amplification process in the outer hair cells of the inner ear. We investigated the influence of different levels of contralateral broadband noise on distortion product otoacoustic emissions in humans, with a particular focus on the quadratic distortion product at f2-f1. The primary stimulus frequency ratio was optimized to yield maximum f2-f1 level. While the cubic distortion product at 2f1-f2 was not significantly affected during contralateral noise stimulation, the level of f2-f1 was reduced by up to 4.8dB on average (maximum: 10.1dB), with significant suppression occurring for noise levels as low as 40dB SPL. In addition, a significant phase lead was observed. Quadratic distortions are minimal at a symmetrical position of the transfer function of the cochlear amplifier. The observed sensitivity of f2-f1 to contralateral noise stimulation could hence be resulting from a shift of the operating state and/or a change in the gain of the cochlear amplification due to contralateral induced efferent modulation of the outer hair cell properties.

Strain-dependence of age-related cochlear hearing loss in wild and domesticated Mongolian gerbils.

The Mongolian gerbil (Meriones unguiculatus) is one of the animal models in auditory research that has been used in several studies on age-related hearing loss. The standard laboratory strain is domesticated as it was bred in captivity for more than 70 years. We compared properties of distortion product otoacoustic emissions (DPOAEs) in domesticated gerbils with wild-type gerbils from F6-F7 generations of a strain originating from animals trapped in Central Asia in 1995. Up to an age of 9months, DPOAE thresholds were comparable between both strains and were below 10dB SPL for f2 frequencies between 4 and 44kHz. In older domesticated animals, the thresholds were increased by up to 12dB. Significant increases were found at stimulus frequencies of 2kHz, 12-20kHz, and 56-60kHz. The best frequency ratio f2/f1 to evoke maximum DPOAE amplitude was larger in domesticated animals at the age of 9 months or older. While these data show that there is a deterioration of cochlear sensitivity due to domestication, the magnitude of the described changes is small. Thus, the general suitability of domesticated gerbils for auditory research seems not to be affected.

Discrimination of direction in fast frequency-modulated tones by rats.

Fast frequency modulations (FM) are an essential part of species-specific auditory signals in animals as well as in human speech. Major parameters characterizing non-periodic frequency modulations are the direction of frequency change in the FM sweep (upward/downward) and the sweep speed, i.e., the speed of frequency change. While it is well established that both parameters are represented in the mammalian central auditory pathway, their importance at the perceptual level in animals is unclear. We determined the ability of rats to discriminate between upward and downward modulated FM-tones as a function of sweep speed in a two-alternative-forced-choice-paradigm. Directional discrimination in logarithmic FM-sweeps was reduced with increasing sweep speed between 20 and 1,000 octaves/s following a psychometric function. Average threshold sweep speed for FM directional discrimination was 96 octaves/s. This upper limit of perceptual FM discrimination fits well the upper limit of preferred sweep speeds in auditory neurons and the upper limit of neuronal direction selectivity in the rat auditory cortex and midbrain, as it is found in the literature. Influences of additional stimulus parameters on FM discrimination were determined using an adaptive testing-procedure for efficient threshold estimation based on a maximum likelihood approach. Directional discrimination improved with extended FM sweep range between two and five octaves. Discrimination performance declined with increasing lower frequency boundary of FM sweeps, showing an especially strong deterioration when the boundary was raised from 2 to 4 kHz. This deterioration corresponds to a frequency-dependent decline in direction selectivity of FM-encoding neurons in the rat auditory cortex, as described in the literature. Taken together, by investigating directional discrimination of FM sweeps in the rat we found characteristics at the perceptual level that can be related to several aspects of FM encoding in the central auditory pathway.

Complexity and temporal dynamics of frequency coding in the awake rat auditory cortex.

Auditory cortical neurons are elements of a neuronal network that decomposes sounds into spectral and temporal information. In particular, their frequency selectivity has been investigated in great detail. Most studies used anaesthetized preparations and found mainly simple V-shaped tuning. The few data available from awake animals indicate that more complex forms of spectral receptive fields, i.e. frequency response areas, can be found there. We investigated frequency response areas in the awake rat primary auditory cortex using statistical evaluation and found complex forms of frequency response areas with several separate subregions in many neurons, besides classical V-shaped tuning. Response areas, as determined with narrow band noise, were very similar to those measured with pure tones. Their width was well correlated to the response strength to white noise stimulation. These results suggest that the excitatory subregions of frequency response areas were the neurons' predominant characteristic, relevant also for the processing of more complex types of stimuli. Investigating the spectrotemporal dynamics of frequency response areas revealed that approximately one-third of the neurons showed long-lasting excitatory or inhibitory components in addition to the typical ON-response. Inhibition was usually of longer duration and occurred mainly in frequency ranges outside the range of initial excitatory responses. These results indicate that auditory cortical neurons in awake animals can represent spectrotemporal information of rather different complexity.

Precognitive and cognitive elements in sound localization.

Sound localization behavior is of great importance for an animal's survival. To localize a sound, animals have to detect a sound source and assign a location to it. In this review we discuss recent results on the underlying mechanisms and on modulatory influences in the barn owl, an auditory specialist with very well developed capabilities to localize sound. Information processing in the barn owl auditory pathway underlying the computations of detection and localization is well understood. This analysis of the sensory information primarily determines the following orienting behavior towards the sound source. However, orienting behavior may be modulated by cognitive (top-down) influences such as attention. We show how advanced stimulation techniques can be used to determine the importance of different cues for sound localization in quasi-realistic stimulation situations, how attentional influences can improve the response to behaviorally relevant stimuli, and how attention can modulate related neural responses. Taken together, these data indicate how sound localization might function in the usually complex natural environment.