Coding Deficits Research Articles

Synaptopathy in the Aging Cochlea: Characterizing Early-Neural Deficits in Auditory Temporal Envelope Processing.

Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age.SIGNIFICANCE STATEMENT Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.

Ensemble coding of face identity is present but weaker in congenital prosopagnosia

Individuals with congenital prosopagnosia (CP) are impaired at identifying individual faces but do not appear to show impairments in extracting the average identity from a group of faces (known as ensemble coding). However, possible deficits in ensemble coding in a previous study (CPs n = 4) may have been masked because CPs relied on pictorial (image) cues rather than identity cues. Here we asked whether a larger sample of CPs (n = 11) would show intact ensemble coding of identity when availability of image cues was minimised. Participants viewed a “set” of four faces and then judged whether a subsequent individual test face, either an exemplar or a “set average”, was in the preceding set. Ensemble coding occurred when matching (vs. mismatching) averages were mistakenly endorsed as set members. We assessed both image- and identity-based ensemble coding, by varying whether test faces were either the same or different images of the identities in the set. CPs showed significant ensemble coding in both tasks, indicating that their performance was independent of image cues. As a group, CPs’ ensemble coding was weaker than controls in both tasks, consistent with evidence that perceptual processing of face identity is disrupted in CP. This effect was driven by CPs (n= 3) who, in addition to having impaired face memory, also performed particularly poorly on a measure of face perception (CFPT). Future research, using larger samples, should examine whether deficits in ensemble coding may be restricted to CPs who also have substantial face perception deficits.

The second agent effect: Interpersonal predictive coding in people with schizophrenia

ABSTRACTInterpersonal predictive coding (IPC) enables one to use the information conveyed by the communicative action of one agent to predict the response of another agent. IPC relies both on explicit reflective processes (processing of communicative intentions) and automatic reflexive processes (motor resonance). Predictive coding deficits may underlie positive symptoms in people with schizophrenia (SCZ), yet IPC has not been analyzed in SCZ. Thirty-nine SCZ and 22 controls (HC) completed a simultaneous masking detection task, during which they observed either communicative (Com) or individual (Ind) actions of agent A and had to report the presence of the agent B, who was shown in half of the trials. In line with previous findings, detection criterion was lowered after Com as compared to Ind, suggesting a higher tendency to report the presence of a second agent after observing agent A’s communicative gestures . Surprisingly, this effect was found to a similar extent in both groups. Communicative criterion was linked to mentalizing abilities, but not to symptoms in SCZ. Finding that SCZ show similar IPC as HC adds to the previous evidence that reflexive processes may be relatively intact in patients. Furthermore, the level of reflective processes may be crucial for patients’ social functioning.

Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage

Higher stages of central auditory processing compensate for a loss of cochlear nerve synapses by increasing the gain on remaining afferent inputs, thereby restoring firing rate codes for rudimentary sound features. The benefits of this compensatory plasticity are limited, as the recovery of precise temporal coding is comparatively modest. We reasoned that persistent temporal coding deficits could be ameliorated through modulation of voltage-gated potassium (Kv) channels that regulate temporal firing patterns. Here, we characterize AUT00063, a pharmacological compound that modulates Kv3.1, a high-threshold channel expressed in fast-spiking neurons throughout the central auditory pathway. Patch clamp recordings from auditory brainstem neurons and in silico modeling revealed that application of AUT00063 reduced action potential timing variability and improved temporal coding precision. Systemic injections of AUT00063 in vivo improved auditory synchronization and supported more accurate decoding of temporal sound features in the inferior colliculus and auditory cortex in adult mice with a near-complete loss of auditory nerve afferent synapses in the contralateral ear. These findings suggest modulating Kv3.1 in central neurons could be a promising therapeutic approach to mitigate temporal processing deficits that commonly accompany aging, tinnitus, ototoxic drug exposure or noise damage.

Dysfunctions in striatal microstructure can enhance perceptual decision making through deficits in predictive coding.

An important brain function is to predict upcoming events on the basis of extracted regularities of previous inputs. These predictive coding processes can disturb performance in concurrent perceptual decision-making and are known to depend on fronto-striatal circuits. However, it is unknown whether, and if so, to what extent striatal microstructural properties modulate these processes. We addressed this question in a human disease model of striosomal dysfunction, i.e. X-linked dystonia-parkinsonism (XDP), using high-density EEG recordings and source localization. The results show faster and more accurate perceptual decision-making performance during distraction in XDP patients compared to healthy controls. The electrophysiological data show that sensory memory and predictive coding processes reflected by the mismatch negativity related to lateral prefrontal brain regions were weakened in XDP patients and thus induced less cognitive conflict than in controls as reflected by the N2 event-related potential (ERP). Consequently, attentional shifting (P3a ERP) and reorientation processes (RON ERP) were less pronounced in the XDP group. Taken together, these results suggests that striosomal dysfunction is related to predictive coding deficits leading to a better performance in concomitant perceptual decision-making, probably because predictive coding does not interfere with perceptual decision-making processes. These effects may reflect striatal imbalances between the striosomes and the matrix compartment.

Auditory deficits in amusia extend beyond poor pitch perception

Congenital amusia is a music perception disorder believed to reflect a deficit in fine-grained pitch perception and/or short-term or working memory for pitch. Because most measures of pitch perception include memory and segmentation components, it has been difficult to determine the true extent of pitch processing deficits in amusia. It is also unclear whether pitch deficits persist at frequencies beyond the range of musical pitch. To address these questions, experiments were conducted with amusics and matched controls, manipulating both the stimuli and the task demands. First, we assessed pitch discrimination at low (500Hz and 2000Hz) and high (8000Hz) frequencies using a three-interval forced-choice task. Amusics exhibited deficits even at the highest frequency, which lies beyond the existence region of musical pitch. Next, we assessed the extent to which frequency coding deficits persist in one- and two-interval frequency-modulation (FM) and amplitude-modulation (AM) detection tasks at 500Hz at slow (fm=4Hz) and fast (fm=20Hz) modulation rates. Amusics still exhibited deficits in one-interval FM detection tasks that should not involve memory or segmentation. Surprisingly, amusics were also impaired on AM detection, which should not involve pitch processing. Finally, direct comparisons between the detection of continuous and discrete FM demonstrated that amusics suffer deficits in both coding and segmenting pitch information. Our results reveal auditory deficits in amusia extending beyond pitch perception that are subtle when controlling for memory and segmentation, and are likely exacerbated in more complex contexts such as musical listening.

Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia

BackgroundRecent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. To test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them with the effects of schizophrenia. MethodsIn two separate studies, the N1 component of the event-related potential elicited by speech sounds during vocalization (talk) and passive playback (listen) were compared to assess the degree of N1 suppression during vocalization, a putative measure of auditory predictive coding. In the crossover study, 31 healthy volunteers completed two randomly ordered test days, a saline day and a ketamine day. Event-related potentials during the talk/listen task were obtained before infusion and during infusion on both days, and N1 amplitudes were compared across days. In the case-control study, N1 amplitudes from 34 schizophrenia patients and 33 healthy control volunteers were compared. ResultsN1 suppression to self-produced vocalizations was significantly and similarly diminished by ketamine (Cohen’s d = 1.14) and schizophrenia (Cohen’s d = .85). ConclusionsDisruption of NMDARs causes dysfunction in predictive coding during vocalization in a manner similar to the dysfunction observed in schizophrenia patients, consistent with the theorized contribution of NMDAR hypofunction to predictive coding deficits in schizophrenia.

Deficits in context-dependent adaptive coding of reward in schizophrenia.

Theoretical principles of information processing and empirical findings suggest that to efficiently represent all possible rewards in the natural environment, reward-sensitive neurons have to adapt their coding range dynamically to the current reward context. Adaptation ensures that the reward system is most sensitive for the most likely rewards, enabling the system to efficiently represent a potentially infinite range of reward information. A deficit in neural adaptation would prevent precise representation of rewards and could have detrimental effects for an organism’s ability to optimally engage with its environment. In schizophrenia, reward processing is known to be impaired and has been linked to different symptom dimensions. However, despite the fundamental significance of coding reward adaptively, no study has elucidated whether adaptive reward processing is impaired in schizophrenia. We therefore studied patients with schizophrenia (n=27) and healthy controls (n=25), using functional magnetic resonance imaging in combination with a variant of the monetary incentive delay task. Compared with healthy controls, patients with schizophrenia showed less efficient neural adaptation to the current reward context, which leads to imprecise neural representation of reward. Importantly, the deficit correlated with total symptom severity. Our results suggest that some of the deficits in reward processing in schizophrenia might be due to inefficient neural adaptation to the current reward context. Furthermore, because adaptive coding is a ubiquitous feature of the brain, we believe that our findings provide an avenue in defining a general impairment in neural information processing underlying this debilitating disorder.

Coding Deficits in Noise-Induced Hidden Hearing Loss May Stem from Incomplete Repair of Ribbon Synapses in the Cochlea.

Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs) and type I afferent auditory nerve fibers (ANFs) may occur in the absence of permanent threshold shift (PTS), and that synapses connecting IHCs with low spontaneous rate (SR) ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise-induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., “hidden hearing loss”). However, significant noise-induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval.

Loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated in the young but not old brain

A dramatic shift in societal demographics will lead to rapid growth in the number of older people with hearing deficits. Poorer performance in suprathreshold speech understanding and temporal processing with age has been previously linked with progressing inner hair cell (IHC) synaptopathy that precedes age-dependent elevation of auditory thresholds. We compared central sound responsiveness after acoustic trauma in young, middle-aged, and older rats. We demonstrate that IHC synaptopathy progresses from middle age onward and hearing threshold becomes elevated from old age onward. Interestingly, middle-aged animals could centrally compensate for the loss of auditory fiber activity through an increase in late auditory brainstem responses (late auditory brainstem response wave) linked to shortening of central response latencies. In contrast, old animals failed to restore central responsiveness, which correlated with reduced temporal resolution in responding to amplitude changes. These findings may suggest that cochlear IHC synaptopathy with age does not necessarily induce temporal auditory coding deficits, as long as the capacity to generate neuronal gain maintains normal sound-induced central amplitudes.

Coding deficits in hidden hearing loss induced by noise: the nature and impacts.

Hidden hearing refers to the functional deficits in hearing without deterioration in hearing sensitivity. This concept is proposed based upon recent finding of massive noise-induced damage on ribbon synapse between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea without significant permanent threshold shifts (PTS). Presumably, such damage may cause coding deficits in auditory nerve fibers (ANFs). However, such deficits had not been detailed except that a selective loss of ANFs with low spontaneous rate (SR) was reported. In the present study, we investigated the dynamic changes of ribbon synapses and the coding function of ANF single units in one month after a brief noise exposure that caused a massive damage of ribbon synapses but no PTS. The synapse count and functional response measures indicates a large portion of the disrupted synapses were re-connected. This is consistent with the fact that the change of SR distribution due to the initial loss of low SR units is recovered quickly. However, ANF coding deficits were developed later with the re-establishment of the synapses. The deficits were found in both intensity and temporal processing, revealing the nature of synaptopathy in hidden hearing loss.

Individual differences in hearing-impaired data: Stats, troubles, and approaches

Individual differences in hearing ability might be dominated by subcomponents of hearing loss, e.g., cochlear gain loss, cochlear neuropathy, temporal coding deficits in low/high frequency regions, or combinations of these components. Unfortunately, we can only rely on indirect and hypothesis-driven objective (e.g., OAE/ABR/EFR) and psychoacoustic threshold metrics that aim to quantify these subcomponents of hearing loss, complicating a straightforward explanation of study results. Because correlations statistics often rely on small listener groups in which each data point could have resulted from different SNRs, metric-specific variability, it is not always clear which correlations are significant and meaningful. Additionally, multiple measures provide a multitude of correlations that should all support the common underlying hypothesis before conclusions can be drawn. In this tutorial, I provide some examples and approaches to more (and less) meaningful correlations based on recently collected objective and psychoacoustic measures in a group of normal and hearing-impaired listeners. Finally, I will introduce how computational model approaches might direct the interpretation of experimental results when several interacting sources of hearing impairment impact outcome measures unexpectedly.

Distorted Tonotopic Coding of Temporal Envelope and Fine Structure with Noise-Induced Hearing Loss

People with cochlear hearing loss have substantial difficulty understanding speech in real-world listening environments (e.g., restaurants), even with amplification from a modern digital hearing aid. Unfortunately, a disconnect remains between human perceptual studies implicating diminished sensitivity to fast acoustic temporal fine structure (TFS) and animal studies showing minimal changes in neural coding of TFS or slower envelope (ENV) structure. Here, we used general system-identification (Wiener kernel) analyses of chinchilla auditory nerve fiber responses to Gaussian noise to reveal pronounced distortions in tonotopic coding of TFS and ENV following permanent, noise-induced hearing loss. In basal fibers with characteristic frequencies (CFs) >1.5 kHz, hearing loss introduced robust nontonotopic coding (i.e., at the wrong cochlear place) of low-frequency TFS, while ENV responses typically remained at CF. As a consequence, the highest dominant frequency of TFS coding in response to Gaussian noise was 2.4 kHz in noise-overexposed fibers compared with 4.5 kHz in control fibers. Coding of ENV also became nontonotopic in more pronounced cases of cochlear damage. In apical fibers, more classical hearing-loss effects were observed, i.e., broadened tuning without a significant shift in best frequency. Because these distortions and dissociations of TFS/ENV disrupt tonotopicity, a fundamental principle of auditory processing necessary for robust signal coding in background noise, these results have important implications for understanding communication difficulties faced by people with hearing loss. Further, hearing aids may benefit from distinct amplification strategies for apical and basal cochlear regions to address fundamentally different coding deficits. Speech-perception problems associated with noise overexposure are pervasive in today's society, even with modern digital hearing aids. Unfortunately, the underlying physiological deficits in neural coding remain unclear. Here, we used innovative system-identification analyses of auditory nerve fiber responses to Gaussian noise to uncover pronounced distortions in coding of rapidly varying acoustic temporal fine structure and slower envelope cues following noise trauma. Because these distortions degrade and diminish the tonotopic representation of temporal acoustic features, a fundamental principle of auditory processing, the results represent a critical advancement in our understanding of the physiological bases of communication disorders. The detailed knowledge provided by this work will help guide the design of signal-processing strategies aimed at alleviating everyday communication problems for people with hearing loss.

On the Interplay Between Cochlear Gain Loss and Temporal Envelope Coding Deficits.

Hearing impairment is characterized by two potentially coexisting sensorineural components: (i) cochlear gain loss that yields wider auditory filters, elevated hearing thresholds and compression loss, and (ii) cochlear neuropathy, a noise-induced component of hearing loss that may impact temporal coding fidelity of supra-threshold sound. This study uses a psychoacoustic amplitude modulation (AM) detection task in quiet and multiple noise backgrounds to test whether these aspects of hearing loss can be isolated in listeners with normal to mildly impaired hearing ability. Psychoacoustic results were compared to distortion-product otoacoustic emission (DPOAE) thresholds and envelope-following response (EFR) measures. AM thresholds to pure-tone carriers (4 kHz) in normal-hearing listeners depended on temporal coding fidelity. AM thresholds in hearing-impaired listeners were normal, indicating that reduced cochlear gain may counteract how reduced temporal coding fidelity degrades AM thresholds. The amount with which a 1-octave wide masking noise worsened AM detection was inversely correlated to DPOAE thresholds. The narrowband noise masker was shown to impact the hearing-impaired listeners more so than the normal hearing listeners, suggesting that this masker may be targeting a temporal coding deficit. This study offers a window into how psychoacoustic difference measures can be adopted in the differential diagnostics of hearing deficits in listeners with mixed forms of sensorineural hearing loss.

How does aging affect the types of error made in a visual short-term memory 'object-recall' task?

This study examines how normal aging affects the occurrence of different types of incorrect responses in a visual short-term memory (VSTM) object-recall task. Seventeen young (Mean = 23.3 years, SD = 3.76), and 17 normally aging older (Mean = 66.5 years, SD = 6.30) adults participated. Memory stimuli comprised two or four real world objects (the memory load) presented sequentially, each for 650 ms, at random locations on a computer screen. After a 1000 ms retention interval, a test display was presented, comprising an empty box at one of the previously presented two or four memory stimulus locations. Participants were asked to report the name of the object presented at the cued location. Errors rates wherein participants reported the names of objects that had been presented in the memory display but not at the cued location (non-target errors) vs. objects that had not been presented at all in the memory display (non-memory errors) were compared. Significant effects of aging, memory load and target recency on error type and absolute error rates were found. Non-target error rate was higher than non-memory error rate in both age groups, indicating that VSTM may have been more often than not populated with partial traces of previously presented items. At high memory load, non-memory error rate was higher in young participants (compared to older participants) when the memory target had been presented at the earliest temporal position. However, non-target error rates exhibited a reversed trend, i.e., greater error rates were found in older participants when the memory target had been presented at the two most recent temporal positions. Data are interpreted in terms of proactive interference (earlier examined non-target items interfering with more recent items), false memories (non-memory items which have a categorical relationship to presented items, interfering with memory targets), slot and flexible resource models, and spatial coding deficits.

Congenital amusia: A cognitive disorder limited to resolved harmonics and with no peripheral basis

Pitch plays a fundamental role in audition, from speech and music perception to auditory scene analysis. Congenital amusia is a neurogenetic disorder that appears to affect primarily pitch and melody perception. Pitch is normally conveyed by the spectro-temporal fine structure of low harmonics, but some pitch information is available in the temporal envelope produced by the interactions of higher harmonics. Using 10 amusic subjects and 10 matched controls, we tested the hypothesis that amusics suffer exclusively from impaired processing of spectro-temporal fine structure. We also tested whether the inability of amusics to process acoustic temporal fine structure extends beyond pitch by measuring sensitivity to interaural time differences, which also rely on temporal fine structure. Further tests were carried out on basic intensity and spectral resolution. As expected, pitch perception based on spectro-temporal fine structure was impaired in amusics; however, no significant deficits were observed in amusics' ability to perceive the pitch conveyed via temporal-envelope cues. Sensitivity to interaural time differences was also not significantly different between the amusic and control groups, ruling out deficits in the peripheral coding of temporal fine structure. Finally, no significant differences in intensity or spectral resolution were found between the amusic and control groups. The results demonstrate a pitch-specific deficit in fine spectro-temporal information processing in amusia that seems unrelated to temporal or spectral coding in the auditory periphery. These results are consistent with the view that there are distinct mechanisms dedicated to processing resolved and unresolved harmonics in the general population, the former being altered in congenital amusia while the latter is spared.

Egocentric and allocentric navigation strategies in Williams syndrome and typical development

Recent findings suggest that difficulties on small-scale visuospatial tasks documented in Williams syndrome (WS) also extend to large-scale space. In particular, individuals with WS often present with difficulties in allocentric spatial coding (encoding relationships between items within an environment or array). This study examined the effect of atypical spatial processing in WS on large-scale navigational strategies, using a novel 3D virtual environment. During navigation of recently learnt large-scale space, typically developing (TD) children predominantly rely on the use of a sequential egocentric strategy (recalling the sequence of left-right body turns throughout a route), but become more able to use an allocentric strategy between 5 and 10 years of age. The navigation strategies spontaneously employed by TD children between 5 and 10 years of age and individuals with WS were analysed. The ability to use an allocentric strategy on trials where spatial relational knowledge was required to find the shortest route was also examined. Results showed that, unlike TD children, during spontaneous navigation the WS group did not predominantly employ a sequential egocentric strategy. Instead, individuals with WS followed the path until the correct environmental landmarks were found, suggesting the use of a time-consuming and inefficient view-matching strategy for wayfinding. Individuals with WS also presented with deficits in allocentric spatial coding, demonstrated by difficulties in determining short-cuts when required and difficulties developing a mental representation of the environment layout. This was found even following extensive experience in an environment, suggesting that - unlike in typical development - experience cannot contribute to the development of spatial relational processing in WS. This atypical presentation of both egocentric and allocentric spatial encoding is discussed in relation to specific difficulties on small-scale spatial tasks and known atypical cortical development in WS.

Cochlear neuropathy and the coding of supra-threshold sound

Many listeners with hearing thresholds within the clinically normal range nonetheless complain of difficulty hearing in everyday settings and understanding speech in noise. Converging evidence from human and animal studies points to one potential source of such difficulties: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Measures of auditory subcortical steady-state responses (SSSRs) in humans and animals support the idea that the temporal precision of the early auditory representation can be poor even when hearing thresholds are normal. In humans with normal hearing thresholds (NHTs), paradigms that require listeners to make use of the detailed spectro-temporal structure of supra-threshold sound, such as selective attention and discrimination of frequency modulation (FM), reveal individual differences that correlate with subcortical temporal coding precision. Animal studies show that noise exposure and aging can cause a loss of a large percentage of auditory nerve fibers (ANFs) without any significant change in measured audiograms. Here, we argue that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests both behaviorally and in SSSRs in humans. Furthermore, recent studies suggest that noise-induced neuropathy may be selective for higher-threshold, lower-spontaneous-rate nerve fibers. Based on our hypothesis, we suggest some approaches that may yield particularly sensitive, objective measures of supra-threshold coding deficits that arise due to neuropathy. Finally, we comment on the potential clinical significance of these ideas and identify areas for future investigation.

Disruption of the Presynaptic Cytomatrix Protein Bassoon Degrades Ribbon Anchorage, Multiquantal Release, and Sound Encoding at the Hair Cell Afferent Synapse

Inner hair cells (IHCs) of the cochlea use ribbon synapses to transmit auditory information faithfully to spiral ganglion neurons (SGNs). In the present study, we used genetic disruption of the presynaptic scaffold protein bassoon in mice to manipulate the morphology and function of the IHC synapse. Although partial-deletion mutants lacking functional bassoon (Bsn(ΔEx4/5)) had a near-complete loss of ribbons from the synapses (up to 88% ribbonless synapses), gene-trap mutants (Bsn(gt)) showed weak residual expression of bassoon and 56% ribbonless synapses, whereas the remaining 44% had a loosely anchored ribbon. Patch-clamp recordings and synaptic CaV1.3 immunolabeling indicated a larger number of Ca(2+) channels for Bsn(gt) IHCs compared with Bsn(ΔEx4/5) IHCs and for Bsn(gt) ribbon-occupied versus Bsn(gt) ribbonless synapses. An intermediate phenotype of Bsn(gt) IHCs was also found by membrane capacitance measurements for sustained exocytosis, but not for the size of the readily releasable vesicle pool. The frequency and amplitude of EPSCs were reduced in Bsn(ΔEx4/5) mouse SGNs, whereas their postsynaptic AMPA receptor clusters were largely unaltered. Sound coding in SGN, assessed by recordings of single auditory nerve fibers and their population responses in vivo, was similarly affected in Bsn(gt) and Bsn(ΔEx4/5) mice. Both genotypes showed impaired sound onset coding and reduced evoked and spontaneous spike rates. In summary, reduced bassoon expression or complete lack of full-length bassoon impaired sound encoding to a similar extent, which is consistent with the comparable reduction of the readily releasable vesicle pool. This suggests that the remaining loosely anchored ribbons in Bsn(gt) IHCs were functionally inadequate or that ribbon independent mechanisms dominated the coding deficit.

Speech perception abilities for spectrally modified signals in individuals with auditory dys-synchrony

Objective. The objective of the study was to determine the speech perception abilities for spectrally modified speech signals in individuals with auditory dys-synchrony. Study Sample. The speech identification scores of 30 normal hearing and 12 individuals diagnosed as having auditory dys-synchrony were studied. Design. Phonemically balanced words in Kannada developed by were presented unfiltered and filtered at 1700 Hz low-pass and 1700 Hz high-pass cut-off frequencies, and speech identification performance was assessed. Results. Results revealed that there is a highly significant difference in speech identification scores for unfiltered and low-pass filtered words. This difference could be attributed to the physiological coding deficits of low frequency information which are usually coded by phase locked responses in auditory nerve fibers (). Conclusions. Thus, low-pass filtered words can be used as an effective tool to identify individuals with auditory dys-synchrony, especially those who have good speech identification scores in quiet.SumarioObjetivo. El objetivo de este estudio fue determinar las habilidades de percepción del lenguaje con señales de lenguaje espectralmente modificadas en sujetos con disincronía auditiva. Muestra de Estudio. Se estudiaron las puntuaciones de identificación de lenguaje de 30 normo-oyentes y de 12 individuos con diagnóstico de disincronía auditiva. Diseño. Se presentaron palabras fonéticamente balanceadas en Kannada, desarrolladas por sin filtro y con filtro pasa/bajo de 1700 Hz y filtro pasa/alto de corte de frecuencias de 1700 Hz, y se evaluó el rendimiento en la identificación del lenguaje. Resultados. Los resultados revelan que existe una diferencia significativa muy alta en las puntuaciones de identificación de lenguaje para palabras no filtradas y con filtro pasa bajo. Esta diferencia puede ser atribuida al déficit fisiológico de codificación de la información e bajas frecuencias, que usualmente se codifican como respuestas con bloqueo de fase en las fibras del nervio auditivo (). Conclusiones. Por lo tanto, las palabras filtradas pasa bajo pueden usarse como una herramienta útil para identificar personas con disincronía auditiva, especialmente aquellas que tienen buenas puntuaciones para la identificación de lenguaje en silencio.