Hunter, L. L. | bioRxiv Science

bioRxiv2023

A potential acoustic role for CFTR ion channel in conductive hearing loss

Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). The middle ear and eustachian tube could be adversely affected in CF. In this study, we provide evidence of the role of CFTR function in conductive hearing. We developed an in-situ model to determine CFTR dependent fluid secretion in the middle ear using native mouse auditory capsule. A unique middle ear-on-a-chip was developed to address the functional and molecular basis of conductive hearing impairment. Using single-cell transcriptomics, middle ear cell composition and the associated transcriptomic signature were compared between CF and WT groups. A specialized subset of epithelial cells expressed CFTR with an overlapping signature with secretory epithelial cells. Genes related to ciliogenesis, hearing and ossification were significantly altered in CF mice middle ear. Our data suggest that CF middle ear may be at higher risk for conductive hearing loss.

cell biology↗

bioRxiv2019

Listening difficulties in children: Behavior and brain activation produced by dichotic listening of CV syllables

Listening difficulties (LiD), also known as auditory processing disorders, are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD. Previous studies have focused on testing using multiple sequential dichotic digits that carry a substantial memory load and executive control demands. We examined the ability of 6-13 year old children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n=39) or having LiD (n=35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6x36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right (forced, FR) or left (FL) ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening data (correct responses, Laterality Index) were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL) and ILD (0, {+/-} 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic and intelligibility components. Some activated areas (planum temporale, inferior frontal gyrus and orbitofrontal cortex) were correlated with dichotic results in TD children only.\n\nNeither group, age nor report method affected the Laterality Index of right/left recall. However, a significant interaction was found between ear, group and ILD. Children with LiD were more influenced by large ILDs, especially favoring the left ear, than were TD children. Neural activity associated with Speech, Phonetic and Intelligibility sentence cues did not significantly differ between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group.\n\nChildren with LiD were more influenced by large ILDs, especially favoring the left ear, than were TD children and were thus less able to modulate performance through attention, and more driven by the physical properties of the acoustic stimuli.

neuroscience↗