Cortical determinants of loudness perception and auditory hypersensitivity.

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were "sticky", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

Ossicular joint histopathology in cases of age-related hearing loss.

Objectives: Age-related hearing loss (presbycusis) is a prevalent condition traditionally attributed to inner ear dysfunction. Little is known about age-related changes in the ossicular joints or their contribution to presbycusis. Herein, we performed an otopathologic evaluation of the ossicular joints in cases of presbycusis without a clear sensorineural explanation. Methods: Histopathologic analysis of the incudomallear (IM) and incudostapedial (IS) joints was performed in specimens from the National Temporal Bone Registry with audiometrically confirmed presbycusis but without histologically observed sensorineural, strial, or mixed features; deemed cases of "indeterminate" presbycusis. Specimens identified as "indeterminate" presbycusis (IP, n = 18) were compared to specimens with histologically confirmed sensorineural presbycusis (n = 16) and strial presbycusis (n = 11). Presbycutic specimens were also compared to age-matched controls (n = 9) and young controls (n = 14). Results: The synovial space at the center of the IM joint was wider in the IP group (194 ± 36.8 µm) compared to age-matched controls (138 ± 36.5 µm), young controls (149 ± 32.2 µm), and ears with sensorineural presbycusis (148 ± 52.7 µm) (p < .05). The synovial space within the IS joint was wider in the IP group (105 ± 33.0 µm) when compared to age-matched controls (57.9 ± 13.1 µm) and ears with sensorineural presbycusis (62.3 ± 31.2 µm) (p < .05). Conclusion: IP ears have wider IM and IS joints when compared to ears with sensorineural presbycusis and age-matched controls. Findings point to a potential middle ear source of high frequency conductive hearing loss in a subset of presbycutic ears. Level of Evidence: Retrospective study.

Human otopathology in scleroderma.

Objective: Scleroderma is a complex chronic progressive immune-mediated disease that causes fibrosis of the skin and internal organs, and vasculopathy.Ear involvement has been poorly studied in patients with scleroderma. Vasculitic and autoimmune mechanisms are considered as possible etiologies on hearing impairment, however, this etiology still unclear.Herein, we reviewed three cases of scleroderma from a temporal bone repository. Methods: The national temporal bone database was reviewed for cases with scleroderma. Clinical case review and correlative otopathologic analysis. Middle and inner ear otopathologic analysis was performed following hematoxylin and eosin staining under light microscopy. Findings were compared to three age-matched controls. Results: Two patients (three cases) with a history of serologically confirmed scleroderma were identified. Both individuals reported tinnitus and demonstrated bilateral moderate to severe down-sloping sensorineural hearing loss on audiometry. Histologically, the incudomallear joint space was diminished and ossicles appeared demineralized. A loss of hyaline cartilage, and obliteration of the incudomallear and incudostapedial joint synovial spaces was observed. Decreased caliber and intimal hyperplasia of arteries adjacent to ossicles was also identified. Mild diffuse atrophy of stria vascularis in the middle and apical turns of cochlea were found. Hair cell populations were normal. Total spiral ganglion neurons were lower in cases of scleroderma (range 29%-51%) compared to age-matched controls. Conclusion: Fibrosis, inflammation, and vascular changes were observed in the middle and inner ear in patients with scleroderma. Findings have implications for understanding hearing and vestibular dysfunction in this patient population. Level of evidence: Retrospective study.