Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation.

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of the interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDCs). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HCs) and bilaterally congenitally deaf cats (CDCs). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing, the predominant effect of each ear is excitation of the auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.

Congenital deafness reduces alpha-gamma cross-frequency coupling in the auditory cortex.

Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity.

Anodic Polarity Minimizes Facial Nerve Stimulation as a Side Effect of Cochlear Implantation.

One severe side effect of the use of cochlear implants (CI) is coincidental facial nerve stimulation (FNS). Clinical methods to alleviate FNS range from the reprogramming of processor settings to revision surgery. We systematically assessed different changes in CI stimulation modes that have been discussed in the literature as "rescue factors" from FNS: electrode configuration (broad to focused), pulse shape (symmetric biphasic to pseudo-monophasic), and pulse polarity (cathodic to anodic). An FNS was assessed, based on electrophysiological thresholds, in 204 electrically evoked compound action potential (eCAP) input/output functions recorded from 33 ears of 26 guinea pigs. The stimulation level difference between auditory nerve eCAP threshold and FNS threshold was expressed as the eCAP-to-FNS offset. Coincidental FNS occurred in all animals and in 45% of all recordings. A change from monopolar to focused (bipolar, tripolar) configurations minimized FNS. The Euclidean distance between the CI contacts and the facial nerve explained no more than 33% of the variance in FNS thresholds. For both the FNS threshold and the eCAP-to-FNS offset, the change from cathodic to anodic pulse polarity significantly reduced FNS and permitted a gain of 14-71% of the dynamic range of the eCAP response. This "anodic rescue effect" was stronger for pseudo-monophasic pulses as compared to the symmetric biphasic pulse shape. These results provide possible mechanisms underlying recent clinical interventions to alleviate FNS. The "anodic-rescue effect" may offer a non-invasive therapeutic option for FNS in human CI users that should be tested clinically, preferably in combination with current-focusing methods.

Late electrically-evoked compound action potentials as markers for acute micro-lesions of spiral ganglion neurons.

Cochlear implants (CIs) are the treatment of choice for profoundly hearing impaired people. It has been proposed that speech perception in CI users is influenced by the neural health (deafferentation, demyelination and degeneration) of the cochlea, which may be heterogeneous along an individual cochlea. Several options have been put forward to account for these local differences in neural health when fitting the speech processor settings, however with mixed results. The interpretation of the results is hampered by the fact that reliable markers of locally restricted changes in spiral ganglion neuron (SGN) health are lacking. The aim of the study was (i) to establish mechanical micro-lesions in the guinea pig as a model of heterogeneous SGN deafferentation and degeneration and (ii) to assess potential electrophysiological markers that can also be used in human subjects. First, we defined the extent of micro-lesions in normal hearing animals using acoustically-evoked compound action potentials (aCAPs); second, we measured electrically-evoked CAPs (eCAPs) before and after focal lesioning in neomycin-deafened and implanted animals. Therefore, we inserted guinea pig adjusted 6-contact CIs through a cochleostomy in the scala tympani. The eCAP was recorded from a ball electrode at the round window niche in response to monopolar or bipolar, 50 µs/phase biphasic pulses of alternating anodic- and cathodic-leading polarity. To exclude the large electrical artifact from the analysis, we focused on the late eCAP component. We systematically isolated the eCAP parameter that showed local pre- versus post-lesion changes and lesion-target specificity. Histological evaluation of the cleared cochleae revealed focal damage of an average size of 0.0036 mm3 with an apical-basal span of maximal 440 µm. We found that the threshold of the late N2P2 eCAP component was significantly elevated after lesioning when stimulating at basal (near the lesion), but not apical (distant to the lesion) CI contacts. To circumvent the potentially conflicting influence of the apical-basal gradient in eCAP thresholds, we used the polarity effect (PE=cathodic-anodic) as a relative measure. During monopolar stimulation, but not bipolar stimulation, the PE was sensitive to the lesion target and showed significantly better cathodic than anodic thresholds after soma lesions. We conclude that the difference in N2P2 thresholds in response to cathodic versus anodic-leading monopolar stimulation corresponds to the presence of SGN soma damage, and may therefore be a marker for SGN loss. We consider this electrophysiological estimate of local neural health a potentially relevant tool for human applications because of the temporal separation from the stimulation artifact and possible implementation into common eCAP measurements.

Carbon-Nanotube-Coated Surface Electrodes for Cortical Recordings In Vivo.

Current developments of electrodes for neural recordings address the need of biomedical research and applications for high spatial acuity in electrophysiological recordings. One approach is the usage of novel materials to overcome electrochemical constraints of state-of-the-art metal contacts. Promising materials are carbon nanotubes (CNTs), as they are well suited for neural interfacing. The CNTs increase the effective contact surface area to decrease high impedances while keeping minimal contact diameters. However, to prevent toxic dissolving of CNTs, an appropriate surface coating is required. In this study, we tested flexible surface electrocorticographic (ECoG) electrodes, coated with a CNT-silicone rubber composite. First, we describe the outcome of surface etching, which exposes the contact nanostructure while anchoring the CNTs. Subsequently, the ECoG electrodes were used for acute in vivo recordings of auditory evoked potentials from the guinea pig auditory cortex. Both the impedances and the signal-to-noise ratios of coated contacts were similar to uncoated gold contacts. This novel approach for a safe application of CNTs, embedded in a surface etched silicone rubber, showed promising results but did not lead to improvements during acute recordings.

The head turn paradigm to assess auditory laterality in cats: influence of ear position and repeated sound presentation.

In most humans, speech is predominantly processed by the left hemisphere. This auditory laterality was formerly thought to be an exclusive human characteristic, but is now suggested to have pre-human origins. In studies on auditory laterality in nonhuman animals, the head turn paradigm has become very popular due to its non-invasive character. Although there are implications that the head turn direction indicates functional dominance of the contralateral hemisphere in processing a given sound, the validity of the paradigm is under debate. To validate the paradigm via comparison with imaging or electrophysiological methods, it is first necessary to establish turning biases at the individual level. Recently, the domestic cat, a common model in hearing research, has been found to show turning biases at the group level. To assess individual turning asymmetries in cats, we repeatedly presented kitten isolation calls and assessed whether differences in conveyed arousal changed the previously described left-wards lateralisation of conspecific vocalizations. Based on responses to 50 playback presentations (25 of high and 25 of low arousal), we calculated individual head turn indices. Based on the total data set, we found no consistent individual turning bias, irrespective of call category or sex of the receiver. Although the playback paradigm was chosen carefully to reduce any effects of lateralized loudness perception or changes in motivation due to habituation, individual head turn biases changed significantly in concordance with habituation to repeated playback-presentations and was predictable by small deflections in ear position prior to listening. When splitting the data set according to a decline in responsiveness after seven playback presentations, we revealed an initial left turning bias for most of our subjects (i.e., significant at the group level). We propose that this left turning bias is related to right hemisphere dominance in processes like vigilance behaviour or general arousal rather than on auditory processing, as such. Our findings suggest that both the experimental sequence and sound level differences, induced by asymmetric ear positions, strongly influence the outcome of the head turn paradigm and should be taken into account when evaluating auditory laterality at the behavioural level.

Female cats, but not males, adjust responsiveness to arousal in the voice of kittens.

BACKGROUND: The infant cry is the most important communicative tool to elicit adaptive parental behaviour. Sex-specific adaptation, linked to parental investment, may have evolutionary shaped the responsiveness to changes in the voice of the infant cries. The emotional content of infant cries may trigger distinctive responsiveness either based on their general arousing properties, being part of a general affect encoding rule, or based on affective perception, linked to parental investment, differing between species. To address this question, we performed playback experiments using infant isolation calls in a species without paternal care, the domestic cat. We used kitten calls recorded in isolation contexts inducing either Low arousal (i.e., isolation only) or High arousal (i.e., additional handling), leading to respective differences in escape response of the kittens. We predicted that only females respond differently to playbacks of Low versus High arousal kitten isolation calls, based on sex-differences in parental investment. RESULTS: Findings showed sex-specific responsiveness of adult cats listening to kitten isolation calls of different arousal conditions, with only females responding faster towards calls of the High versus the Low arousal condition. Breeding experience of females did not affect the result. Furthermore, female responsiveness correlated with acoustic parameters related to spectral characteristics of the fundamental frequency (F0): Females responded faster to kitten calls with lower F0 at call onset, lower minimum F0 and a steeper slope of the F0. CONCLUSIONS: Our study revealed sex-specific differences in the responsiveness to kitten isolation calls of different arousal conditions independent of female breeding experience. The findings indicated that features of F0 are important to convey the arousal state of an infant. Taken together, the results suggest that differences in parental investment evolutionary shaped responsiveness (auditory sensitivity/ motivation) to infant calls in a sex-specific manner in the domestic cat.

Auditory feedback modulates development of kitten vocalizations.

Effects of hearing loss on vocal behavior are species-specific. To study the impact of auditory feedback on feline vocal behavior, vocalizations of normal-hearing, hearing-impaired (white) and congenitally deaf (white) cats were analyzed at around weaning age. Eleven animals were placed in a soundproof booth for 30 min at different ages, from the first to the beginning of the fourth postnatal month, every 2 weeks of life. In total, 13,874 vocalizations were analyzed using an automated procedure. Firstly, vocalizations were detected and segmented, with voiced and unvoiced vocalizations being differentiated. The voiced isolation calls ('meow') were further analyzed. These vocalizations showed developmental changes affecting several parameters in hearing controls, whereas the developmental sequence was delayed in congenitally deaf cats. In hearing-impaired and deaf animals, we observed differences both in vocal behavior (loudness and duration) and in the calls' acoustic structure (fundamental frequency and higher harmonics). The fundamental frequency decreased with age in all groups, most likely due to maturation of the vocal apparatus. In deaf cats, however, other aspects of the acoustic structure of the vocalizations did not fully mature. The harmonic ratio (i.e., frequency of first harmonic divided by fundamental frequency) was higher and more variable in deaf cats than in the other study groups. Auditory feedback thus affects the acoustic structure of vocalizations and their ontogenetic development. The study suggests that both the vocal apparatus and its neuronal motor control are subject to maturational processes, whereas the latter is additionally dependent on auditory feedback in cats.

Vocal correlates of sender-identity and arousal in the isolation calls of domestic kitten (Felis silvestris catus).

INTRODUCTION: Human speech does not only communicate linguistic information but also paralinguistic features, e.g. information about the identity and the arousal state of the sender. Comparable morphological and physiological constraints on vocal production in mammals suggest the existence of commonalities encoding sender-identity and the arousal state of a sender across mammals. To explore this hypothesis and to investigate whether specific acoustic parameters encode for sender-identity while others encode for arousal, we studied infants of the domestic cat (Felis silvestris catus). Kittens are an excellent model for analysing vocal correlates of sender-identity and arousal. They strongly depend on the care of their mother. Thus, the acoustical conveyance of sender-identity and arousal may be important for their survival. RESULTS: We recorded calls of 18 kittens in an experimentally-induced separation paradigm, where kittens were spatially separated from their mother and siblings. In the Low arousal condition, infants were just separated without any manipulation. In the High arousal condition infants were handled by the experimenter. Multi-parametric sound analyses revealed that kitten isolation calls are individually distinct and differ between the Low and High arousal conditions. Our results suggested that source- and filter-related parameters are important for encoding sender-identity, whereas time-, source- and tonality-related parameters are important for encoding arousal. CONCLUSION: Comparable findings in other mammalian lineages provide evidence for commonalities in non-verbal cues encoding sender-identity and arousal across mammals comparable to paralinguistic cues in humans. This favours the establishment of general concepts for voice recognition and emotions in humans and animals.

Paw preference is not affected by postural demand in a nonprimate mammal (Felis silvestris catus).

Previously, it has been thought that handedness is unique to humans. Recently, it has been found that hand or paw preferences are common among a variety of vertebrate species. Different models have been put forth to describe the evolution of primate handedness. In this study we aimed to explore whether these models can also be used to predict manual laterality in nonprimate mammalian groups. The cat (Felis silvestris catus) is a good nonprimate model for manual laterality, as cats frequently use paws to catch and hold prey. Cats were exposed to two standardized manual laterality tasks, differing in postural demand. Subjects (N = 28) were forced to use either a stable or unstable body posture (i.e., sitting or standing vs. vertical clinging) to extract food items from a plastic box attached at two different heights. We revealed that cats exhibited paw preferences at an individual level with about 40% left, 30% right, 30% nonlateralized subjects. Postural demand was linked to task difficulty: the unstable body posture was found to be significantly more difficult than the stable body posture. However, these differences in postural demand and task difficulty did not lead to differences in direction or strength of paw preference. Findings suggested that nonprimate mammals differ from primates in their sensitivity to task related factors, such as postural demand. Results coincide with those of some prosimians, providing support for the hypothesis that postural demand and the associated task complexity became influencing factors on manual laterality in the course of primate evolution.

Is acoustic evaluation in a non-primate mammal, the tree shrew, affected by context?

Sound categorisation plays a crucial role for processing ecological and social stimuli in a species' natural environment. To explore the discrimination and evaluation of sound stimuli in human babies and nonhuman primates, a reciprocal habituation-dishabituation paradigm has been successfully introduced into auditory research. We applied the reciprocal paradigm for the first time to a non-primate mammal, the tree shrew (Tupaia belangeri), to examine to what extent non-primate mammals share the ability to evaluate communication calls with primates. Playback stimuli were three types of communication calls, differing distinctively in context and acoustic structure, as well as two artificial control sounds, differing solely in frequency. We assessed the attention towards the playback stimuli by the latency to respond to the test stimulus. Subjects evaluated pairs of communication call types as well as the artificial playback stimuli. Attention towards the test stimuli differed significantly in strength for one pair of communication calls, with subjects dishabituating faster to one category than the other. The comparison of a second pair of communication calls did not show significant differences. Interestingly, subjects also evaluated the artificial control sounds. Findings are only partly in line with results on human and non-human primates. They provided first evidence that in non-primate mammals acoustic evaluation is not solely affected by the sound-associated context but is also linked to unusualness and acoustic cues, such as peak frequency.