The perception of ultrasonic vocalizations by laboratory mice following intense noise exposures.

Noise-induced hearing loss interacts with age, sex, and listening conditions to affect individuals' perception of ecologically relevant stimuli like speech. The present experiments assessed the impact of age and sex on vocalization detection by noise-exposed mice trained to detect a downsweep or complex ultrasonic vocalization in quiet or in the presence of a noise background. Daily thresholds before and following intense noise exposure were collected longitudinally and compared across several factors. All mice, regardless of age, sex, listening condition, or stimulus type showed their poorest behavioral sensitivity immediately after the noise exposure. There were varying degrees of recovery over time and across factors. Old-aged mice had greater threshold shifts and less recovery compared to middle-aged mice. Mice had larger threshold shifts and less recovery for downsweeps than for complex vocalizations. Female mice were more sensitive, had smaller post-noise shifts, and had better recovery than males. Thresholds in noise were higher and less variable than thresholds in quiet, but there were comparable shifts and recovery. In mice, as in humans, the perception of ecologically relevant stimuli suffers after an intense noise exposure, and results differ from simple tone detection findings.

Blast trauma affects production and perception of mouse ultrasonic vocalizations.

Blast trauma from explosions affects hearing and communication in a significant proportion of soldiers. Many veterans report difficulty communicating, especially in noisy and reverberant environments, which contributes to complex mental health problems including anxiety and depression. However, the relationship between communication and perceptual problems after a blast has received little scientific attention. In the current studies, the effects of blast trauma on the production and perception of ultrasonic vocalizations (USVs) by CBA/CaJ mice, a common animal model for hearing and communication disorders, was explored. Overall, mice change the total number of vocalizations, the proportion produced of each syllable category, and the peak frequency, bandwidth, and duration of their vocalizations after blast exposure. Further, the perception of USVs is affected after blast trauma, with an immediate worsening of detection for most USV categories in the first 1-5 days after blasts, which later recovers. This study is the first to examine changes in the production and perception of communication signals after blast traumas in mice and is an important step towards developing treatments for blast-induced hearing and communication disorders.

Sources of variability in auditory brainstem response thresholds in a mouse model of noise-induced hearing loss.

Numerous and non-acoustic experimental factors can potentially influence experimental outcomes in animal models when measuring the effects of noise exposures. Subject-related factors, including species, strain, age, sex, body weight, and post-exposure measurement timepoints, influence the observed hearing deficits. Experimenter effects, such as experience with experimental techniques and animal handling, may also factor into reported thresholds. In this study, the influence of subject sex, body mass, age at noise exposure, and timepoint of post-exposure recording are reported from a large sample of CBA/CaJ mice. Auditory brainstem response (ABR) thresholds differed between noise-exposed and unexposed mice, although the differences varied across tone frequencies. Thresholds across age at noise exposures and measurement delays after exposure also differed for some timepoints. Higher body mass correlated with higher ABR thresholds for unexposed male and female mice, but not for noise-exposed mice. Together, these factors may contribute to differences in phenotypic outcomes observed across studies or even within a single laboratory.

The effects of age and sex on the detection of pure tones by adult CBA/CaJ mice (Mus musculus).

Age-related hearing loss (ARHL) is a neurodegenerative disorder characterized by a gradual decrease in hearing sensitivity. Previous electrophysiological and behavioral studies have demonstrated that the CBA/CaJ mouse strain is an appropriate model for the late-onset hearing loss found in humans. However, few studies have characterized hearing in these mice behaviorally using longitudinal methodologies. The goal of this research was to utilize a longitudinal design and operant conditioning procedures with positive reinforcement to construct audiograms and temporal integration functions in aging CBA/CaJ mice. In the first experiment, thresholds were collected for 8, 16, 24, 42, and 64 kHz pure tones in 30 male and 35 female CBA/CaJ mice. Similar to humans, mice had higher thresholds for high frequency tones than for low frequency pure tones across the lifespan. Female mice had better hearing acuity than males after 645 days of age. In the second experiment, temporal integration functions were constructed for 18 male and 18 female mice for 16 and 64 kHz tones varying in duration. Mice showed an increase in thresholds for tones shorter than 200 ms, reaching peak performance at shorter durations than other rodent species. Overall, CBA/CaJ mice experience ARHL for pure tones of different frequencies and durations, making them a good model for studies on hearing loss. These findings highlight the importance of using a wide range of stimuli and a longitudinal design when comparing presbycusis across different species.

Best sensitivity of temporal modulation transfer functions in laboratory mice matches the amplitude modulation embedded in vocalizations.

The perception of spectrotemporal changes is crucial for distinguishing between acoustic signals, including vocalizations. Temporal modulation transfer functions (TMTFs) have been measured in many species and reveal that the discrimination of amplitude modulation suffers at rapid modulation frequencies. TMTFs were measured in six CBA/CaJ mice in an operant conditioning procedure, where mice were trained to discriminate an 800 ms amplitude modulated white noise target from a continuous noise background. TMTFs of mice show a bandpass characteristic, with an upper limit cutoff frequency of around 567 Hz. Within the measured modulation frequencies ranging from 5 Hz to 1280 Hz, the mice show a best sensitivity for amplitude modulation at around 160 Hz. To look for a possible parallel evolution between sound perception and production in living organisms, we also analyzed the components of amplitude modulations embedded in natural ultrasonic vocalizations (USVs) emitted by this strain. We found that the cutoff frequency of amplitude modulation in most of the individual USVs is around their most sensitive range obtained from the psychoacoustic experiments. Further analyses of the duration and modulation frequency ranges of USVs indicated that the broader the frequency ranges of amplitude modulation in natural USVs, the shorter the durations of the USVs.

Behavioral measurements of auditory streaming and build-up by budgerigars (Melopsittacus undulatus).

The perception of the build-up of auditory streaming has been widely investigated in humans, while it is unknown whether animals experience a similar perception when hearing high (H) and low (L) tonal pattern sequences. The paradigm previously used in European starlings (Sturnus vulgaris) was adopted in two experiments to address the build-up of auditory streaming in budgerigars (Melopsittacus undulatus). In experiment 1, different numbers of repetitions of low-high-low triplets were used in five conditions to study the build-up process. In experiment 2, 5 and 15 repetitions of high-low-high triplets were used to investigate the effects of repetition rate, frequency separation, and frequency range of the two tones on the birds' streaming perception. Similar to humans, budgerigars subjectively experienced the build-up process in auditory streaming; faster repetition rates and larger frequency separations enhanced the streaming perception, and these results were consistent across the two frequency ranges. Response latency analysis indicated that the budgerigars needed a longer amount of time to respond to stimuli that elicited a salient streaming perception. These results indicate, for the first time using a behavioral paradigm, that budgerigars experience a build-up of auditory streaming in a manner similar to humans.

Discrimination of frequency modulated sweeps by mice.

Mice often produce ultrasonic vocalizations (USVs) that sweep upwards in frequency from around 60 to around 80 kHz and downwards in frequency from 80 to 60 kHz. Whether or not these USVs are used for communication purposes is still unknown. Here, mice were trained and tested using operant conditioning procedures and positive reinforcement to discriminate between synthetic upsweeps and downsweeps. The stimuli varied in bandwidth, duration, and direction of sweep. The mice performed significantly worse when discriminating between background and test stimuli when the stimuli all occupied the same bandwidths. Further, the mice's discrimination performance became much worse for stimuli that had durations similar to those natural vocalizations of the mice. Sweeps composed of different frequency ranges and longer durations had improved discrimination. These results collected using artificial stimuli created to mimic natural USVs indicate that the bandwidth of the vocalizations may be much more important for communication than the frequency contours of the vocalizations.

Cues for auditory stream segregation of birdsong in budgerigars and zebra finches: Effects of location, timing, amplitude, and frequency.

Deciphering the auditory scene is a problem faced by many organisms. However, when faced with numerous overlapping sounds from multiple locations, listeners are still able to attribute the individual sound objects to their individual sound-producing sources. Here, the characteristics of sounds important for integrating versus segregating in birds were determined. Budgerigars and zebra finches were trained using operant conditioning procedures on an identification task to peck one key when they heard a whole zebra finch song and to peck another when they heard a zebra finch song missing a middle syllable. Once the birds were trained to a criterion performance level on those stimuli, probe trials were introduced on a small proportion of trials. The probe songs contained modifications of the incomplete training song's missing syllable. When the bird responded as if the probe was a whole song, it suggests they streamed together the altered syllable and the rest of the song. When the bird responded as if the probe was a non-whole song, it suggests they segregated the altered probe from the rest of the song. Results show that some features, such as location and intensity, are more important for segregating than other features, such as timing and frequency.

Discrimination of partial from whole ultrasonic vocalizations using a go/no-go task in mice.

Mice are a commonly used model in hearing research, yet little is known about how they perceive conspecific ultrasonic vocalizations (USVs). Humans and birds can distinguish partial versions of a communication signal, and discrimination is superior when the beginning of the signal is present compared to the end of the signal. Since these effects occur in both humans and birds, it was hypothesized that mice would display similar facilitative effects with the initial portions of their USVs. Laboratory mice were tested on a discrimination task using operant conditioning procedures. The mice were required to discriminate incomplete versions of a USV target from a repeating background containing the whole USV. The results showed that the mice had difficulty discriminating incomplete USVs from whole USVs, especially when the beginning of the USVs were presented. This finding suggests that the mice perceive the initial portions of a USV as more similar to the whole USV than the latter parts of the USV, similar to results from humans and birds.

The inferior colliculus encodes the Franssen auditory spatial illusion.

Illusions are effective tools for the study of the neural mechanisms underlying perception because neural responses can be correlated to the physical properties of stimuli and the subject's perceptions. The Franssen illusion (FI) is an auditory spatial illusion evoked by presenting a transient, abrupt tone and a slowly rising, sustained tone of the same frequency simultaneously on opposite sides of the subject. Perception of the FI consists of hearing a single sound, the sustained tone, on the side that the transient was presented. Both subcortical and cortical mechanisms for the FI have been proposed, but, to date, there is no direct evidence for either. The data show that humans and rhesus monkeys perceive the FI similarly. Recordings were taken from single units of the inferior colliculus in the monkey while they indicated the perceived location of sound sources with their gaze. The results show that the transient component of the Franssen stimulus, with a shorter first spike latency and higher discharge rate than the sustained tone, encodes the perception of sound location. Furthermore, the persistent erroneous perception of the sustained stimulus location is due to continued excitation of the same neurons, first activated by the transient, by the sustained stimulus without location information. These results demonstrate for the first time, on a trial-by-trial basis, a correlation between perception of an auditory spatial illusion and a subcortical physiological substrate.

Dimensionally Specific Attention Capture in Birds Performing Auditory Streaming Task.

Previous studies in budgerigars (Melopsittacus undulatus) have indicated that they experience attention capture in a qualitatively similar way to humans. Here, we apply a similar objective auditory streaming paradigm, using modified budgerigar vocalizations instead of ABAB-… patterned pure tones, in the sound sequences. The birds were trained to respond to deviants in the target stream while ignoring the distractors in the background stream. The background distractor could vary among five different categories and two different sequential positions, while the target deviants could randomly appear at five different sequential positions and vary among two different categories. We found that unpredictable background distractors could deteriorate birds' sensitivity to the target deviants. Compared to conditions where the background distractor appeared right before the target deviant, the attention capture effect decayed in conditions when the background distractor appeared earlier. In contrast to results from the same paradigm using pure tones, the results here are evidence for a faster recovery from attention capture using modified vocalization segments. We found that the temporally modulated background distractor captured birds' attention more and deteriorated birds' performance more than other categories of background distractor, as the temporally modulated target deviant enabled the birds to focus their attention toward the temporal modulation dimension. However, different from humans, birds have lower tolerances for suppressing the distractors from the same feature dimensions as the targets, which is evidenced by higher false alarm rates for the temporally modulated distractor than other distractors from different feature dimensions.

Effects of Noise Exposure and Aging on Behavioral Tone Detection in Quiet and Noise by Mice.

Aging leads to degeneration of the peripheral and central auditory systems, hearing loss, and difficulty understanding sounds in noise. Aging is also associated with changes in susceptibility to or recovery from damaging noise exposures, although the effects of the interaction between acute noise exposure and age on the perception of sounds are not well studied. We tested these effects in the CBA/CaJ mouse model of age-related hearing loss using operant conditioning procedures before and after noise exposure and longitudinally measured changes in their sensitivity for detecting tones in quiet or noise backgrounds. Cochleae from a subset of the behaviorally tested mice were immunolabeled to examine organ of Corti damage relative to what is expected based on aging alone. Mice tested in both quiet and noise background conditions experienced worse behavioral sensitivity immediately after noise exposure, but mice exposed at older ages generally showed greater threshold shifts and reduced recovery over time. Surprisingly, day-to-day stability in thresholds was markedly higher for mice detecting signals in the presence of a noise masker compared with detection in quiet conditions. Cochlear analysis revealed decreases in the total number of outer hair cells (OHCs) and the number of ribbons per inner cell in high-frequency regions in aged, noise-exposed mice relative to aging alone. Our findings build on previous work showing interactions between age and noise exposure and add that background noise can increase the stability of behavioral hearing sensitivity after noise damage.

Lateralization of acoustic signals by dichotically listening budgerigars (Melopsittacus undulatus).

Sound localization allows humans and animals to determine the direction of objects to seek or avoid and indicates the appropriate position to direct visual attention. Interaural time differences (ITDs) and interaural level differences (ILDs) are two primary cues that humans use to localize or lateralize sound sources. There is limited information about behavioral cue sensitivity in animals, especially animals with poor sound localization acuity and small heads, like budgerigars. ITD and ILD thresholds were measured behaviorally in dichotically listening budgerigars equipped with headphones in an identification task. Budgerigars were less sensitive than humans and cats, and more similar to rabbits, barn owls, and monkeys, in their abilities to lateralize dichotic signals. Threshold ITDs were relatively constant for pure tones below 4 kHz, and were immeasurable at higher frequencies. Threshold ILDs were relatively constant over a wide range of frequencies, similar to humans. Thresholds in both experiments were best for broadband noise stimuli. These lateralization results are generally consistent with the free field localization abilities of these birds, and add support to the idea that budgerigars may be able to enhance their cues to directional hearing (e.g., via connected interaural pathways) beyond what would be expected based on head size.

Identification of auditory distance cues by zebra finches (Taeniopygia guttata) and budgerigars (Melopsittacus undulatus).

The present study examined auditory distance perception cues in a non-territorial songbird, the zebra finch (Taeniopygia guttata), and in a non-songbird, the budgerigar (Melopsittacus undulatus). Using operant conditioning procedures, three zebra finches and three budgerigars were trained to identify 1- (Near) and 75-m (Far) recordings of three budgerigar contact calls, one male zebra finch song, and one female zebra finch call. Once the birds were trained on these endpoint stimuli, other stimuli were introduced into the operant task. These stimuli included recordings at intermediate distances and artificially altered stimuli simulating changes in overall amplitude, high-frequency attenuation, reverberation, and all three cues combined. By examining distance cues (amplitude, high-frequency attenuation, and reverberation) separately, this study sought to determine which cue was the most salient for the birds. The results suggest that both species could scale the stimuli on a continuum from Near to Far and that amplitude was the most important cue for these birds in auditory distance perception, as in humans and other animals.

Long term changes to auditory sensitivity following blast trauma in mice.

Blast trauma is a common acoustic/physical insult occurring in modern warfare. Twenty percent of active duty military come into close proximity to explosions and experience mild to severe sensory deficits. The prevalence of such injuries is high but correlating auditory sensitivity changes with the initial insult is difficult because injury and evaluations are often separated by long time periods. Here, auditory sensitivity was measured before and after a traumatic blast in adult CBA/CaJ mice using auditory brainstem responses, distortion production otoacoustic emissions, and behavioral detection of pure tones. These measurements included baseline auditory sensitivity prior to injury in all mice, and again at 3, 30, and 90 days after the blast in the two physiological groups, and daily for up to 90 days in the behavioral group. Mice in all groups experienced an initial deterioration in auditory sensitivity, though physiological measurements showed evidence of recovery that behavioral measurements did not. Amplitudes and latencies of ABR waves may reflect additional changes beyond the peripheral damage shown by the threshold changes and should be explored further. The present work addresses a major gap in the current acoustic trauma literature both in terms of comparing physiological and behavioral methods, as well as measuring the time course of recovery.

Attention capture in birds performing an auditory streaming task.

Numerous animal models have been used to investigate the neural mechanisms of auditory processing in complex acoustic environments, but it is unclear whether an animal's auditory attention is functionally similar to a human's in processing competing auditory scenes. Here we investigated the effects of attention capture in birds performing an objective auditory streaming paradigm. The classical ABAB… patterned pure tone sequences were modified and used for the task. We trained the birds to selectively attend to a target stream and only respond to the deviant appearing in the target stream, even though their attention may be captured by a deviant in the background stream. When no deviant appeared in the background stream, the birds experience the buildup of streaming process in a qualitatively similar way as they did in a subjective paradigm. Although the birds were trained to selectively attend to the target stream, they failed to avoid the involuntary attention switch caused by the background deviant, especially when the background deviant was sequentially unpredictable. Their global performance deteriorated more with increasingly salient background deviants, where the buildup process was reset by the background distractor. Moreover, sequential predictability of the background deviant facilitated the recovery of the buildup process after attention capture. This is the first study that addresses the perceptual consequences of the joint effects of top-down and bottom-up attention in behaving animals.

Linking anatomical and physiological markers of auditory system degeneration with behavioral hearing assessments in a mouse (Mus musculus) model of age-related hearing loss.

Age-related hearing loss is a very common sensory disability, affecting one in three older adults. Establishing a link between anatomical, physiological, and behavioral markers of presbycusis in a mouse model can improve the understanding of this disorder in humans. We measured age-related hearing loss for a variety of acoustic signals in quiet and noisy environments using an operant conditioning procedure and investigated the status of peripheral structures in CBA/CaJ mice. Mice showed the greatest degree of hearing loss in the last third of their lifespan, with higher thresholds in noisy than in quiet conditions. Changes in auditory brainstem response thresholds and waveform morphology preceded behavioral hearing loss onset. Loss of hair cells, auditory nerve fibers, and signs of stria vascularis degeneration were observed in old mice. The present work underscores the difficulty in ascribing the primary cause of age-related hearing loss to any particular type of cellular degeneration. Revealing these complex structure-function relationships is critical for establishing successful intervention strategies to restore hearing or prevent presbycusis.

Behaviorally measured audiograms and gap detection thresholds in CBA/CaJ mice.

Tone detection and temporal gap detection thresholds were determined in CBA/CaJ mice using a Go/No-go procedure and the psychophysical method of constant stimuli. In the first experiment, audiograms were constructed for five CBA/CaJ mice. Thresholds were obtained for eight pure tones ranging in frequency from 1 to 42 kHz. Audiograms showed peak sensitivity between 8 and 24 kHz, with higher thresholds at lower and higher frequencies. In the second experiment, thresholds for gap detection in broadband and narrowband noise bursts were measured at several sensation levels. For broadband noise, gap thresholds were between 1 and 2 ms, except at very low sensation levels, where thresholds increased significantly. Gap thresholds also increased significantly for low pass-filtered noise bursts with a cutoff frequency below 18 kHz. Our experiments revised absolute auditory thresholds in the CBA/CaJ mouse strain and demonstrated excellent gap detection ability in the mouse. These results add to the baseline behavioral data from normal-hearing mice which have become increasingly important for assessing auditory abilities in genetically altered mice.

Effects of syllable-final segment duration on the identification of synthetic speech continua by birds and humans.

In an attempt to test whether experience with or knowledge of language is necessary to show typical speaking rate effects in the perception of speech, budgerigars (Melopsittacus undulatus) and humans categorized stimuli from the synthetic continua /ba/-/wa/ and /bas/-/was/, with both short and long syllable-final phonemes. This comparative approach aims to shed some light on whether knowledge of language has a role in rate normalization effects, such as using duration information as an indicator of speaking rate in human speech perception. Syllable-final phoneme durations were varied, and were either temporally adjacent to the initial target (CV series) or were nonadjacent (CVC series). The birds were always influenced by syllable-final duration variation in the present experiments and displayed greater boundary shifts than humans. In humans, there was a significant boundary shift observed in the CV series, but there were no effects of duration variation in the final segment in the CVC series. The results from the birds suggest that specialized speech-based principles may not be necessary for explaining findings of grouping speech or speechlike elements in perception.

Perception of Ultrasonic Vocalizations by Socially Housed and Isolated Mice.

It is currently unclear whether mice use their ultrasonic vocalizations (USVs) for communication purposes. It is also unknown whether mice require previous experience with USVs to understand conspecifics. There is some evidence that experience changes the perception of juvenile USVs; however, it is unclear whether similar plasticity also occurs for adult USVs. To examine whether social exposure or deprivation throughout development leads to changes in USV perception, eleven female CBA/CaJ mice were trained to discriminate between 18 USVs of three different categories using operant conditioning procedures. Mice were group housed with four females or housed individually from weaning for the duration of the experiment. Socially housed and isolated mice differed in initial training times on pure tones, suggesting isolated mice had a more difficult time learning the task. Both groups completed USV discrimination conditions quicker at the end of the testing phases relative to the beginning. The overall discrimination of USVs did not differ between the two housing conditions, but a multidimensional scaling analysis revealed that socially experienced and isolated mice perceive some USVs differently, illustrated by differences in locations of USVs on the scaling maps from the two groups. Finally, a negative correlation was found between spectrotemporal similarity and percent discrimination, and analyses support the idea that mice may show categorical perception of at least two of the three USV categories. Thus, experience with USVs changes USV perception.