Allison Oliva

Hypothesis: Electrical stimulation of the external ear mediates cardiovascular changes in anesthetized rats. Background: Auricular vagus nerve stimulation (aVNS) has been proposed as a noninvasive treatment for cardiovascular disease. Stimulation is typically achieved via electrodes placed on the external ear, but the exact mechanisms by which aVNS induces cardiovascular changes remains unclear. In particular, the relative contributions of sympathetic and parasympathetic pathways have not been well elucidated. In this study, we use a rodent model to determine the hemodynamic effects of stimulating two auricular regions and assess the autonomic pathways mediating these responses. Methods: Bipolar transcutaneous electrical stimulation was applied to the external ear of adult Sprague-Dawley rats. Cardiovascular parameters including mean arterial pressure (MAP), photoplethysmography (PPG), and cardiac electrical activity were recorded. Cervical vagotomies and hexamethonium sympathetic blockade were performed to assess the parasympathetic and sympathetic contributions to evoked cardiovascular responses. Results: Electrical stimulation at the concha resulted in significant changes in MAP and PPG. MAP changes were larger with stimulation in the concha compared with the anterior pinna. MAP responses increased in a dose-dependent manner with increasing current amplitude. Bilateral vagotomy resulted in persistent but decreased evoked cardiovascular responses. Complete autonomic blockade using intravenous hexamethonium resulted in the absence of any evoked cardiovascular responses with aVNS. Conclusion: Cardiovascular changes from aVNS are mediated by modulation of both parasympathetic and sympathetic activity.

Hypothesis: A novel adeno-associated virus (AAV) can be used to label the sensory nerves of the external ear in mice. Background: Stimulation of the auricular branch of the vagus nerve (ABVN) has been proposed as a noninvasive approach to vagus nerve stimulation. Here, we use a recently introduced AAV with enhanced tropism for peripheral sensory neurons (AAV-PHP.S) to label the somatosensory nerves of the external ear, including the ABVN. Methods: AAV-PHP.S capsids with a Cre-dependent fluorescent reporter cargo were injected retro-orbitally into 9 adult transgenic mice. Sensory ganglia for cranial nerves V, VII, IX, X, along with cervical dorsal root ganglia (DRG) and the external ear, were harvested. Immunohistochemistry was used to visualize expression of the reporter, tdTomato, in ganglion neurons and in sensory afferent nerve fibers in the external ear. Results: Eight of the 9 injected animals showed expression in all the relevant ganglia (CN V, VII, IX, X, and DRG). Expression was quantified in the jugular ganglion of the vagus nerve (which houses the cell bodies of the ABVN); 15.8%±1.3% of the neurons in this ganglion were successfully transduced with a fluorescent reporter (tdTomato). In 8 of the 9 animals, we also detected reporter expression in sensory nerve fibers in the external ear. We quantified the expression of the reporter in the external ear and found that the majority of nerve fiber area (66%±18%) strongly expressed tdTomato. Conclusion: AAV-PHP.S can be used to transduce the sensory nerves of the external ear in mice, including the ABVN.

Background/Objectives: Single-sided deafness (SSD) treatment options include Contralateral Routing of Signal (CROS) or Bilateral Routing of Signal (BiCROS) systems, bone conduction devices, cochlear implants (CIs) and no intervention. Aligning treatment recommendations with patient motivations is fundamental for satisfaction and successful outcomes. At our institution, a structured telehealth consultation precedes formal testing and includes treatment motivation exploration and comprehensive review of all interventions. This study examined SSD treatment motivations and their association with pursuing cochlear implantation. Methods: Adults who completed a pre-treatment SSD telehealth consultation over a four-year period were identified. Charts were retrospectively reviewed for demographics, SSD characteristics, treatment motivations, treatment choice, and CI outcomes. Results: A total of 122 adults were evaluated. Mean age was 56.3 (±13.0) years, and 59.8% were male. Mean SSD duration was 10.8 (±15.8) years. The most common etiology was sudden sensorineural hearing loss. The top primary motivations were improving overall hearing (23.0%), restoring hearing to the deaf ear (22.1%), and improving hearing in noise (21.3%). Most patients (45.1%) opted for a hearing aid, CROS or BiCROS system; 38.5% chose CI; and 14.8% declined treatment. Only 57.4% of those who selected CI had the implant, primarily due to surgery avoidance (31.5%) and insurance limitations (10.5%). Motivation did not predict treatment choice or CI receipt. Among CI recipients (n = 27), those motivated by hearing restoration demonstrated poorer speech outcomes and datalogging. Conclusions: Improving overall hearing and restoring hearing to the deaf ear were the most common motivations for seeking SSD treatment. Adult CI recipients had similar motivations to those who chose non-surgical options.

BACKGROUND. Presbyosmia, or aging-related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction and is subject to acquired damage, suggesting a likely site of pathology in aging. Adult stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis. Methods. Accordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. The study combined psychophysical testing with olfactory mucosa biopsy analysis, single-cell RNA-Sequencing (scRNA-Seq), and culture studies. Results. We identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress or the regulation of proliferation and differentiation. Using a culture model, we found that cytokine exposure drove increased TP63, a transcription factor acting to prevent OE stem cell differentiation. Conclusions. Our data suggest aging-related inflammatory changes in OE stem cells may contribute to presbyosmia via the disruption of normal epithelial homeostasis. OE stem cells may represent a therapeutic target for restoration of olfaction. Funding. NIH grants DC018371, NS121067, DC016224; Office of Physician-Scientist Development, Burroughs-Wellcome Fund Research Fellowship for Medical Students Award, Duke University School of Medicine.

Purpose: The purpose of this study was to determine the test–retest reliability and the minimum detectable change (MDC) scores of the Listening Self-Efficacy Questionnaire (LSEQ). Method: A total of 77 older adults who were experienced hearing aid users were administered the LSEQ in pen–paper format on two separate occasions. They were provided the first copy of the LSEQ in the clinic to take home to complete. Those participants who completed and returned the first copy of the questionnaire were then mailed a second copy of the LSEQ to complete and return approximately 2 weeks later. The mean subscale and total scale scores from the two administrations were compared using intraclass correlation coefficients (ICCs) to determine test–retest reliability of the measure. The MDC scores, or the minimum difference between scores to demonstrate a real change in self-efficacy levels, were also calculated for each subscale and the total scale. Results: The ICCs ranged from 0.786 to 0.920 for the subscale and total scale scores. The MDC scores for the subscale and total scale ranged from 14.3% to 19.1%. Conclusions: The results of this study indicate that the LSEQ has moderate to excellent test–retest reliability. The MDC scores demonstrate that the LSEQ has the potential to detect true changes in listening self-efficacy in older patients with hearing loss who use hearing aids. The LSEQ may aid clinicians in understanding listening self-efficacy in their patients and how their self-efficacy levels change with amplification.