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 eight weeks 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 while 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 pre-trauma 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) while 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.

Disturbed Balance of Inhibitory Signaling Links Hearing Loss and Cognition

Neuronal hyperexcitability in the central auditory pathway linked to reduced inhibitory activity is associated with numerous forms of hearing loss, including noise damage, age-dependent hearing loss, and deafness, as well as tinnitus or auditory processing deficits in autism spectrum disorder (ASD). In most cases, the reduced central inhibitory activity and the accompanying hyperexcitability are interpreted as an active compensatory response to the absence of synaptic activity, linked to increased central neural gain control (increased output activity relative to reduced input). We here suggest that hyperexcitability also could be related to an immaturity or impairment of tonic inhibitory strength that typically develops in an activity-dependent process in the ascending auditory pathway with auditory experience. In these cases, high-SR auditory nerve fibers, which are critical for the shortest latencies and lowest sound thresholds, may have either not matured (possibly in congenital deafness or autism) or are dysfunctional (possibly after sudden, stressful auditory trauma or age-dependent hearing loss linked with cognitive decline). Fast auditory processing deficits can occur despite maintained basal hearing. In that case, tonic inhibitory strength is reduced in ascending auditory nuclei, and fast inhibitory parvalbumin positive interneuron (PV-IN) dendrites are diminished in auditory and frontal brain regions. This leads to deficits in central neural gain control linked to hippocampal LTP/LTD deficiencies, cognitive deficits, and unbalanced extra-hypothalamic stress control. Under these conditions, a diminished inhibitory strength may weaken local neuronal coupling to homeostatic vascular responses required for the metabolic support of auditory adjustment processes. We emphasize the need to distinguish these two states of excitatory/inhibitory imbalance in hearing disorders: (i) Under conditions of preserved fast auditory processing and sustained tonic inhibitory strength, an excitatory/inhibitory imbalance following auditory deprivation can maintain precise hearing through a memory linked, transient disinhibition that leads to enhanced spiking fidelity (central neural gain⇑) (ii) Under conditions of critically diminished fast auditory processing and reduced tonic inhibitory strength, hyperexcitability can be part of an increased synchronization over a broader frequency range, linked to reduced spiking reliability (central neural gain⇓). This latter stage mutually reinforces diminished metabolic support for auditory adjustment processes, increasing the risks for canonical dementia syndromes.

Synaptic mechanisms of top-down control in the non-lemniscal inferior colliculus

Corticofugal projections to evolutionarily ancient, subcortical structures are ubiquitous across mammalian sensory systems. These ‘descending’ pathways enable the neocortex to control ascending sensory representations in a predictive or feedback manner, but the underlying cellular mechanisms are poorly understood. Here, we combine optogenetic approaches with in vivo and in vitro patch-clamp electrophysiology to study the projection from mouse auditory cortex to the inferior colliculus (IC), a major descending auditory pathway that controls IC neuron feature selectivity, plasticity, and auditory perceptual learning. Although individual auditory cortico-collicular synapses were generally weak, IC neurons often integrated inputs from multiple corticofugal axons that generated reliable, tonic depolarizations even during prolonged presynaptic activity. Latency measurements in vivo showed that descending signals reach the IC within 30 ms of sound onset, which in IC neurons corresponded to the peak of synaptic depolarizations evoked by short sounds. Activating ascending and descending pathways at latencies expected in vivo caused a NMDA receptor-dependent, supralinear excitatory postsynaptic potential summation, indicating that descending signals can nonlinearly amplify IC neurons’ moment-to-moment acoustic responses. Our results shed light upon the synaptic bases of descending sensory control and imply that heterosynaptic cooperativity contributes to the auditory cortico-collicular pathway’s role in plasticity and perceptual learning.

Neural tracking as an objective measure of auditory perception and speech intelligibility

The neural tracking framework enables the analysis of neural responses (EEG) to continuous natural speech, e.g., a story or a podcast. This allows for objective investigation of a range of auditory and linguistic processes in the brain during natural speech perception. This approach is more ecologically valid than traditional auditory evoked responses and has great potential for both research and clinical applications. In this article, we review the neural tracking framework and highlight three prominent examples of neural tracking analyses. This includes the neural tracking of the fundamental frequency of the voice (f0), the speech envelope and linguistic features. Each of these analyses provides a unique point of view into the hierarchical stages of speech processing in the human brain. f0-tracking assesses the encoding of fine temporal information in the early stages of the auditory pathway, i.e. from the auditory periphery up to early processing in the primary auditory cortex. This fundamental processing in (mostly) subcortical stages forms the foundation of speech perception in the cortex. Envelope tracking reflects bottom-up and top-down speech-related processes in the auditory cortex, and is likely necessary but not sufficient for speech intelligibility. To study neural processes more directly related to speech intelligibility, neural tracking of linguistic features can be used. This analysis focuses on the encoding of linguistic features (e.g. word or phoneme surprisal) in the brain. Together these analyses form a multi-faceted and time-effective objective assessment of the auditory and linguistic processing of an individual.

Comparative study of brainstem evoked response audiometry in diabetic patients and non-diabetic subjects to assess the involvement of central auditory pathway

<p><strong>Background: </strong>Diabetes mellitus (DM) which is prevalent in world is associated with sensorineural hearing loss. Brainstem evoked response audiometry (BERA) is a simple, non-invasive procedure to detect early impairment of acoustic nerve and auditory pathway. The present study is under taken to evaluate the impact of DM on BERA parameters. Aim of the study was to compare the BERA of diabetic patients to those of age and gender matched controls to assess the involvement of central auditory pathway.</p><p><strong>Methods</strong>: A cross sectional study was conducted on 35 diabetic patients, aged 35 to 55 years, who were on treatment for at least 2 years, and 35 age and sex matched control participants, were subjected for BERA at 70,80 and 90 dB. The waveforms, absolute latency of wave I, wave III, wave V and interwave/ inter peak latency of I-III, III-V and I-V were analyzed with respect to both groups.</p><p><strong>Results</strong>: The absolute latency of wave III and wave V, interpeak/ interwave latency of I-III, interpeak/ interwave latency of I-V, III-V and absolute latency of wave V were highly significant at corresponding tested stimuli in the diabetic group compared to the control group.</p><p><strong>Conclusions</strong>: Early involvement of central auditory pathway in diabetic patients, can be detected with fair accuracy with auditory evoked potential studies; if done on a regular basis warrants meticulous glycemic control and prevents further damage.</p>

Expression Patterns of the Neuropeptide Urocortin 3 and Its Receptor CRFR2 in the Mouse Central Auditory System

Sensory systems have to be malleable to context-dependent modulations occurring over different time scales, in order to serve their evolutionary function of informing about the external world while also eliciting survival-promoting behaviors. Stress is a major context-dependent signal that can have fast and delayed effects on sensory systems, especially on the auditory system. Urocortin 3 (UCN3) is a member of the corticotropin-releasing factor family. As a neuropeptide, UCN3 regulates synaptic activity much faster than the classic steroid hormones of the hypothalamic-pituitary-adrenal axis. Moreover, due to the lack of synaptic re-uptake mechanisms, UCN3 can have more long-lasting and far-reaching effects. To date, a modest number of studies have reported the presence of UCN3 or its receptor CRFR2 in the auditory system, particularly in the cochlea and the superior olivary complex, and have highlighted the importance of this stress neuropeptide for protecting auditory function. However, a comprehensive map of all neurons synthesizing UCN3 or CRFR2 within the auditory pathway is lacking. Here, we utilize two reporter mouse lines to elucidate the expression patterns of UCN3 and CRFR2 in the auditory system. Additional immunolabelling enables further characterization of the neurons that synthesize UCN3 or CRFR2. Surprisingly, our results indicate that within the auditory system, UCN3 is expressed predominantly in principal cells, whereas CRFR2 expression is strongest in non-principal, presumably multisensory, cell types. Based on the presence or absence of overlap between UCN3 and CRFR2 labeling, our data suggest unusual modes of neuromodulation by UCN3, involving volume transmission and autocrine signaling.

PET/CT background noise and its effect on speech recognition

Positron emission tomography (PET) has been successfully used to investigate central nervous processes, including the central auditory pathway. Unlike early water-cooled PET-scanners, novel PET/CT scanners employ air cooling and include a CT system, both of which result in higher background noise levels. In the present study, we describe the background noise generated by two state-of-the-art air-cooled PET/CT scanners. We measured speech recognition in background noise: recorded PET noise and a speech-shaped noise applied in clinical routine to subjects with normal hearing. Background noise produced by air-cooled PET/CT is considerable: 75.1 dB SPL (64.5 dB(A)) for the Philips Gemini TF64 and 76.9 dB SPL (68.4 dB(A)) for the Philips Vereos PET/CT (Philips Healthcare, The Netherlands). Subjects with normal hearing exhibited better speech recognition in recorded PET background noise compared with clinically applied speech-shaped noise. Speech recognition in both background noises correlated significantly. Background noise generated by PET/CT scanners should be considered when PET is used for the investigation of the central auditory pathway. Speech in PET noise is better than in speech-shaped noise because of the minor masking effect of the background noise of the PET/CT.