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The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research.

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INTRODUCTION: The functional evaluation of auditory-nerve activity in spontaneous conditions has remained elusive in humans. In animals, the frequency analysis of the round-window electrical noise recorded by means of electrocochleography yields a frequency peak at around 900 to 1000 Hz, which has been proposed to reflect auditory-nerve spontaneous activity. Here, we studied the spectral components of the electrical noise obtained from cochlear implant electrocochleography in humans. METHODS: We recruited adult cochlear implant recipients from the Clinical Hospital of the Universidad de Chile, between the years 2021 and 2022. We used the AIM System from Advanced Bionics® to obtain single trial electrocochleography signals from the most apical electrode in cochlear implant users. We performed a protocol to study spontaneous activity and auditory responses to 0.5 and 2 kHz tones. RESULTS: Twenty subjects including 12 females, with a mean age of 57.9 ± 12.6 years (range between 36 and 78 years) were recruited. The electrical noise of the single trial cochlear implant electrocochleography signal yielded a reliable peak at 3.1 kHz in 55% of the cases (11 out of 20 subjects), while an oscillatory pattern that masked the spectrum was observed in seven cases. In the other two cases, the single-trial noise was not classifiable. Auditory stimulation at 0.5 kHz and 2.0 kHz did not change the amplitude of the 3.1 kHz frequency peak. CONCLUSION: We found two main types of noise patterns in the frequency analysis of the single-trial noise from cochlear implant electrocochleography, including a peak at 3.1 kHz that might reflect auditory-nerve spontaneous activity, while the oscillatory pattern probably corresponds to an artifact.

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Introduction: Frailty is a geriatric syndrome frequently associated with executive dysfunction and white matter hyperintensities (WMH). But the relation between executive dysfunction and brain changes is poorly understood in frail subjects. Our hypothesis is that frontal-WMH mediates the association between frailty and executive dysfunction. Methods: A convenience sample of 113 subjects older than 65 years without dementia was studied with neuropsychological test, a structured clinical interview, physical examination and brain MRI. They were classified as robust or pre-frail and frail using the frailty phenotype score (0-5). The frontal WMH (F-WMH) were manually graduated (0-6) using the "Age-Related White Matter Changes score" from FLAIR sequences at a 3 Tesla brain MRI. A mediation analysis was done for testing whether F-WMH could act as a link factor between frailty phenotype score and executive dysfunction. Results: The group's mean age was 74 ± 6 years, subjects with higher frailty score had more depressive symptoms and worse performance in executive function tests. A regression analysis that explained 52% of the variability in executive functions, revealed a significant direct effect of frailty score (Standardized ßcoeff [95% CI] -0.201, [-0.319, -0.049], and F-WMH (-0.152[-0.269, -0.009]) on executive functions, while the F-WMH showed a small partial mediation effect between frailty and executive functions (-0.0395, [-0.09, -0.004]). Discussion: Frontal matter hyperintensities had a small mediation effect on the association between frailty and executive dysfunction, suggesting that other neuropathological and neurofunctional changes might also be associated with executive dysfunction in frail subjects.

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Age-related hearing loss is linked to cognitive impairment, but the mechanisms that relate to these conditions remain unclear. Evidence shows that the activation of medial olivocochlear (MOC) neurons delays cochlear aging and hearing loss. Consequently, the loss of MOC function may be related to cognitive impairment. The α9/α10 nicotinic receptor is the main target of cholinergic synapses between the MOC neurons and cochlear outer hair cells. Here, we explored spatial learning and memory performance in middle-aged wild-type (WT) and α9-nAChR subunit knock-out (KO) mice using the Barnes maze and measured auditory brainstem response (ABR) thresholds and the number of cochlear hair cells as a proxy of cochlear aging. Our results show non-significant spatial learning differences between WT and KO mice, but KO mice had a trend of increased latency to enter the escape box and freezing time. To test a possible reactivity to the escape box, we evaluated the novelty-induced behavior using an open field and found a tendency towards more freezing time in KO mice. There were no differences in memory, ABR threshold, or the number of cochlear hair cells. We suggest that the lack of α9-nAChR subunit alters novelty-induced behavior, but not spatial learning in middle-aged mice, by a non-cochlear mechanism.

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Introduction: The mechanisms underlying tinnitus perception are still under research. One of the proposed hypotheses involves an alteration in top-down processing of auditory activity. Low-frequency oscillations in the delta and theta bands have been recently described in brain and cochlear infrasonic signals during selective attention paradigms in normal hearing controls. Here, we propose that the top-down oscillatory activity observed in brain and cochlear signals during auditory and visual selective attention in normal subjects, is altered in tinnitus patients, reflecting an abnormal functioning of the corticofugal pathways that connect brain circuits with the cochlear receptor. Methods: To test this hypothesis, we used a behavioral task that alternates between auditory and visual top-down attention while we simultaneously measured electroencephalogram (EEG) and distortion-product otoacoustic emissions (DPOAE) signals in 14 tinnitus and 14 control subjects. Results: We found oscillatory activity in the delta and theta bands in cortical and cochlear channels in control and tinnitus patients. There were significant decreases in the DPOAE oscillatory amplitude during the visual attention period as compared to the auditory attention period in tinnitus and control groups. We did not find significant differences when using a between-subjects statistical approach comparing tinnitus and control groups. On the other hand, we found a significant cluster in the delta band in tinnitus when using within-group statistics to compare the difference between auditory and visual DPOAE oscillatory power. Conclusion: These results confirm the presence of top-down infrasonic low-frequency cochlear oscillatory activity in the delta and theta bands in tinnitus patients, showing that the corticofugal suppression of cochlear oscillations during visual and auditory attention in tinnitus patients is preserved.

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(1) Background: Persistent postural-perceptual dizziness (PPPD) is a common chronic dizziness disorder with an unclear pathophysiology. It is hypothesized that PPPD may involve disrupted spatial cognition processes as a core feature. (2) Methods: A cohort of 19 PPPD patients underwent psycho-cognitive testing, including assessments for anxiety, depression, memory, attention, planning, and executive functions, with an emphasis on spatial navigation via a virtual Morris water maze. These patients were compared with 12 healthy controls and 20 individuals with other vestibular disorders but without PPPD. Vestibular function was evaluated using video head impulse testing and vestibular evoked myogenic potentials, while brain magnetic resonance imaging was used to exclude confounding pathology. (3) Results: PPPD patients demonstrated unique impairments in allocentric spatial navigation (as evidenced by the virtual Morris water maze) and in other high-demand visuospatial cognitive tasks that involve executive functions and planning, such as the Towers of London and Trail Making B tests. A factor analysis highlighted spatial navigation and advanced visuospatial functions as being central to PPPD, with a strong correlation to symptom severity. (4) Conclusions: PPPD may broadly impair higher cognitive functions, especially in spatial cognition. We discuss a disruption in the creation of enriched cognitive spatial maps as a possible pathophysiology for PPPD.

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Cholinergic transmission is essential for survival and reproduction, as it is involved in several physiological responses. In the auditory system, both ascending and descending auditory pathways are modulated by cholinergic transmission, affecting the perception of sounds. The auditory efferent system is a neuronal network comprised of several feedback loops, including corticofugal and brainstem pathways to the cochlear receptor. The auditory efferent system's -final and mandatory synapses that connect the brain with the cochlear receptor- involve medial olivocochlear neurons and outer hair cells. A unique cholinergic transmission mediates these synapses through α9/α10 nicotinic receptors. To study this receptor, it was generated a strain of mice carrying a null mutation of the Chrna9 gene (α9-KO mice), lacking cholinergic transmission between medial olivocochlear neurons and outer hair cells, providing a unique opportunity to study the role of medial olivocochlear cholinergic transmission in auditory and cognitive functions. In this article, we review behavioral and physiological studies carried out to research auditory efferent function in the context of audition, cognition, and hearing impairments. Auditory studies have shown that hearing thresholds in the α9-KO mice are normal, while more complex auditory functions, such as frequency selectivity and sound localization, are altered. The corticofugal pathways have been studied in α9-KO mice using behavioral tasks, evidencing a reduced capacity to suppress auditory distractors during visual selective attention. Finally, we discuss the evolutionary role of the auditory efferent system detecting vocalizations in noise and its role in auditory disorders, such as the prevention of age-related hearing loss.

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Artificial intelligence-assisted otologic diagnosis has been of growing interest in the scientific community, where middle and external ear disorders are the most frequent diseases in daily ENT practice. There are some efforts focused on reducing medical errors and enhancing physician capabilities using conventional artificial vision systems. However, approaches with multispectral analysis have not yet been addressed. Tissues of the tympanic membrane possess optical properties that define their characteristics in specific light spectra. This work explores color wavelengths dependence in a model that classifies four middle and external ear conditions: normal, chronic otitis media, otitis media with effusion, and earwax plug. The model is constructed under a computer-aided diagnosis system that uses a convolutional neural network architecture. We trained several models using different single-channel images by taking each color wavelength separately. The results showed that a single green channel model achieves the best overall performance in terms of accuracy (92%), sensitivity (85%), specificity (95%), precision (86%), and F1-score (85%). Our findings can be a suitable alternative for artificial intelligence diagnosis systems compared to the 50% of overall misdiagnosis of a non-specialist physician.

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Presbycusis or age-related hearing loss is a prevalent condition in the elderly population, which affects oral communication, especially in background noise, and has been associated with social isolation, depression, and cognitive decline. However, the mechanisms that relate hearing loss with cognition are complex and still elusive. Importantly, recent studies show that the use of hearing aids in presbycusis, which is its standard management, can induce neuroplasticity and modify performance in cognitive tests. As the majority of the previous studies on audition and cognition obtained their results from a mixed sample of subjects, including presbycusis individuals fitted and not fitted with hearing aids, here, we revisited the associations between hearing loss and cognition in a controlled sample of unaided presbycusis. We performed a cross-sectional study in 116 non-demented Chilean volunteers aged ≥65 years from the Auditory and Dementia study cohort. Specifically, we explored associations between bilateral sensorineural hearing loss, suprathreshold auditory brain stem responses, auditory processing (AP), and cognition with a comprehensive neuropsychological examination. The AP assessment included speech perception in noise (SIN), dichotic listening (dichotic digits and staggered spondaic words), and temporal processing [frequency pattern (FP) and gap-in-noise detection]. The neuropsychological evaluations included attention, memory, language, processing speed, executive function, and visuospatial abilities. We performed an exploratory factor analysis that yielded four composite factors, namely, hearing loss, auditory nerve, midbrain, and cognition. These four factors were used for generalized multiple linear regression models. We found significant models showing that hearing loss is associated with bilateral SIN performance, while dichotic listening was associated with cognition. We concluded that the comprehension of the auditory message in unaided presbycusis is a complex process that relies on audition and cognition. In unaided presbycusis with mild hearing loss (<40 dB HL), speech perception of monosyllabic words in background noise is associated with hearing levels, while cognition is associated with dichotic listening and FP.