Faculty Bibliography

Most offspring are born helpless, requiring intense caregiving from parents especially during the first few days of neonatal life. For many species, infant cries are a primary signal used by parents to provide caregiving. Previously we and others documented how maternal left auditory cortex rapidly becomes sensitized to pup calls over hours of parental experience, enabled by oxytocin. The speed and robustness of this maternal plasticity suggests cortical pre-tuning or initial bias for pup call stimulus features. Here we examine the circuit basis of left-lateralized tuning to vocalization features with whole-cell recordings in brain slices. We found that layer 2/3 pyramidal cells of female left auditory cortex show selective suppression of inhibitory inputs with repeated stimulation at the fundamental pup call rate (inter-stimulus interval ∼150 msec) in pup-naïve females and expanded with maternal experience. However, optogenetic stimulation of cortical inhibitory cells showed that inputs from somatostatin-positive and oxytocin-receptor-expressing interneurons were less suppressed at these rates. This suggested that disynaptic inhibition rather than monosynaptic depression was a major mechanism underlying pre-tuning of cortical excitatory neurons, confirmed with simulations. Thus cortical interneuron specializations can augment neuroplasticity mechanisms to ensure fast appropriate caregiving in response to infant cries.

OBJECTIVE:To assess the association of race/ethnicity and education status on time to intervention and the total number of interventions in pediatric patients with microtia undergoing hearing intervention and external ear reconstruction. METHODS:A retrospective chart review was performed in pediatric patients diagnosed with congenital ear deformities evaluated by an otolaryngologist or audiologist from January 1, 2013 to December 1, 2021 at a large surgical institution. Variables analyzed included demographics, patient conditions, time to surgery, and number of surgeries. Statistical analysis included analysis of variance, chi-squared tests, and multivariate regression. RESULTS:Disparities were identified in reconstructive microtia repair, with non-White patients having an increased number of external ear reconstructive surgeries (p = 0.004), with Black patients average 2 external ear reconstructive surgeries, Hispanic patients 1.74 surgeries, while White patients averaged 0.812 surgeries. All non-White patients also demonstrated increased total number of surgeries (1.94 Asian, 2.57 Black, 2.11 Hispanic, 3.29 Other/Unknown, vs 1.23 White, p = 0.007) and total number of interventions (2.17 Asian, 2.71 Black, 2.37 Hispanic 3.43 Other/Unknown, vs 1.56 White, p = 0.02) as compared to White patients. In multivariate regression analysis, race was a significant factor influencing the number of reconstructive and overall surgeries, while the presence of aural atresia was the strongest predictor for requiring additional hearing surgery. CONCLUSION/CONCLUSIONS:An increased number of interventions and surgeries were seen amongst non-White patients with microtia. Further investigation is warranted to understand the socioeconomic factors associated with pediatric microtia surgery.

High-density microelectrode arrays have opened new possibilities for systems neuroscience, but brain motion relative to the array poses challenges for downstream analyses. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from action potential data, DREDge enables automated, high-temporal-resolution motion tracking in local field potential data. In human intraoperative recordings, DREDge's local field potential-based tracking reliably recovered evoked potentials and single-unit spike sorting. In recordings of deep probe insertions in nonhuman primates, DREDge tracked motion across centimeters of tissue and several brain regions while mapping single-unit electrophysiological features. DREDge reliably improved motion correction in acute mouse recordings, especially in those made with a recent ultrahigh-density probe. Applying DREDge to recordings from chronic implantations in mice yielded stable motion tracking despite changes in neural activity between experimental sessions. These advances enable automated, scalable registration of electrophysiological data across species, probes and drift types, providing a foundation for downstream analyses of these rich datasets.

OBJECTIVE:Infantile subglottic hemangioma (SGH) poses a risk of airway compromise if untreated. Traditionally, operative endoscopy (OH) diagnoses SGH, but since the discovery of beta-blockers' efficacy in treating infantile hemangiomas (IHs) in 2008, and advances in endoscopic technology, nonoperative methods have emerged. This review identifies endoscopic practices for diagnosing and monitoring infantile SGH during the oral beta-blocker treatment era. DATA SOURCES/METHODS:A comprehensive literature search in October 2022 and August 2023 covered PubMed, Embase, Cochrane Library, SCOPUS, and Web of Science. REVIEW METHODS/METHODS:The search was limited to English-language studies published since 2008, considering this when propranolol was demonstrated as an effective treatment option for IH. The articles were screened for relevance based on predefined inclusion and exclusion criteria. RESULTS:After inclusion and exclusion criteria, sixty final studies were identified, describing 240 cases of infantile SGH. Most children were diagnosed using OE alone (73.3%; n = 176/240), 23.3% (n = 56/240) using office-based laryngoscopy procedures (OBPs) followed by OE, 3.3% using OBP alone (n = 8/240). There were no reported diagnostic endoscopy-related complications. Twenty-nine studies described using endoscopy plus diagnostic imaging to either confirm an SGH lesion, characterize the extent of disease spread, or rule out other causes of presenting symptoms. The proportion of infants diagnosed with OE alone decreased from 2008 to 2023. CONCLUSION/CONCLUSIONS:Operative endoscopy remains the SGH diagnostic standard, but OBP adoption is increasing. Further research is needed to determine the optimal SGH diagnosis and management approach. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 2024.

The pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Targeting macrophage-fibroblast interactions is an interesting therapeutic strategy; macrophages alter their phenotype to mediate both inflammation and fibrosis. In the current study, we investigated concentration-dependent effects of methylprednisolone on the fibrotic response, with an emphasis on YAP/TAZ-TEAD signaling, and inflammatory gene expression in VF fibroblasts in physical contact with macrophages. We sought to provide foundational data to optimize therapeutic strategies for millions of patients with voice/laryngeal disease-related disability. Following induction of inflammatory (M(IFN/LPS)) and fibrotic (M(TGF)) phenotypes, THP-1-derived macrophages were seeded onto HVOX vocal fold fibroblasts. Cells were co-cultured ± 0.3-3000 nM methylprednisolone ± 3 µM verteporfin, a YAP/TAZ inhibitor. Inflammatory (CXCL10, TNF, PTGS2) and fibrotic genes (ACTA2, CCN2, COL1A1) in fibroblasts were analyzed by real-time polymerase chain reaction after cell sorting. Ser211-phosphorylated glucocorticoid receptor (S211-pGR) was assessed by Western blotting. Nuclear localization of S211-pGR and YAP/TAZ was analyzed by immunocytochemistry. Methylprednisolone decreased TNF and PTGS2 in fibroblasts co-cultured with M(IFN/LPS) macrophages and increased ACTA2 and CCN2 in fibroblasts co-cultured with M(IFN/LPS) and M(TGF). Lower concentrations were required to decrease TNF and PTGS2 expression and to increase S211-pGR than to increase ACTA2 and CCN2 expression and nuclear localization of S211-pGR. Methylprednisolone also increased YAP/TAZ nuclear localization. Verteporfin attenuated upregulation of CCN2, but not PTGS2 downregulation. High concentration methylprednisolone induced nuclear localization of S211-pGR and upregulated fibrotic genes mediated by YAP/TAZ activation.

OBJECTIVE:The videofluoroscopic swallow study (VFSS) is an evaluation of the anatomy and physiology of swallowing, and often includes a screening evaluation of the esophagus. How the esophageal screen translates to esophageal pathology remains unknown. The purpose of this study was to determine if abnormal esophageal clearance (EC) on VFSS correlates with esophageal function on high-resolution esophageal manometry (HREM). MATERIALS AND METHODS/METHODS:This is a retrospective review of 115 adult patients who underwent both VFSS with esophageal screen and HRM. EC on VFSS was scored with the modified barium swallow impairment profile (MBSImP) component 17. Motility was characterized using HRM metrics according to the Chicago Classification Version 4.0 (CCv4.0). Predictive metrics were calculated for the esophageal screen. RESULTS:An EC score o greater than or equal to 1 had a sensitivity of 66%, specificity of 57%, PPV of 52%, NPV of 70%, and OR of 2.55 (p = 0.027). EC weakly correlated with incomplete bolus clearance (rho = 0.331, p = 0.0004) and did not correlate with bolus transit time (rho = 0.17, p = 0.105). CONCLUSIONS:The esophageal screen as characterized by the MBSImP is not an effective predictor of esophageal function on HREM as defined by the CCv4.0. Future work may focus on a defining a standardized VFSS protocol for the esophageal screen and potentially a more nuanced assessment of esophageal findings on VFSS that may enhance the sensitivity of the modality to motility disorders.

Oropharyngeal dysphagia is an independent predictor of poor outcomes in many health conditions and can be targeted directly through swallowing therapy. This study aims to explore the outcomes of outpatient swallowing therapy in clinical practice across a diverse cohort of patients. This was a retrospective, single-site longitudinal cohort study. Patients 18 years or older with dysphagia who completed 7-8 weeks of outpatient swallowing therapy with a pre- and post-treatment videofluoroscopy were included. Therapy employed a progressive swallowing exercise regimen based on the Systematic Exercise for Treatment of Swallowing (SETS) protocol. Outcome measures included the pharyngeal components of the Modified Barium Swallow Impairment Profile, penetration-aspiration scale scores, and diet recommendations using the International Dysphagia Diet Standardization Initiative. 152 patients were included. Swallowing therapy improved all MBSImP component scores except 1, 7, and 13. Therapy improved total pharyngeal impairment scores by 2.66 points (p < .001) and total oral impairment score by 1.41 points (p < .001). Odds of elevated aspiration risk were reduced by 49% (p < .001). Patients were more likely to be on an unmodified food consistency after completion of therapy (OR 26, p = .004), but liquid consistency was not altered (OR 2.0, p = .57). Overall, 44% of patients in the cohort with an efficiency issue improved, and 50% of patients at risk for aspiration pre-therapy improved. Completing a 7-8 week course of exercise-based outpatient swallowing therapy is effective at improving multiple measures of swallowing physiology, safety and efficiency. It can also enable relaxation of diet consistency restrictions based on the IDDSI framework.

PURPOSE/OBJECTIVE:Dysphagia is a commonly occurring medical condition estimated to occur in between and 10% adults in the US. Despite this relatively high prevalence, the general population's understanding of this condition is currently unknown. Our aims were to (a) conduct a large-scale survey to determine the public's awareness and understanding of dysphagia in comparison to other three other health conditions and (b) compare this knowledge to relative prevalence rates of the conditions. METHODS:The survey was designed to measure four constructs of interest comparing dysphagia with insomnia, vertigo and ataxia. Constructs included: (1) Knowledge of the Condition, (2) Source of Knowledge, (3) Health Impact, (4) Treating Medical Professionals. The survey was launched via Qualtrics™ software and participants were recruited and paid using Prolific™. Descriptive statistics were used to compare participants knowledge of dysphagia with the other conditions. To obtain relative prevalence rates, Cosmos was used to quantify the number of Epic-based patient encounters with any ICD-10 code for each condition in 2023 and expressed as a percent of all patient encounters in the US in 2023. RESULTS:2000 adults (n = 1030 female) aged 18-95 (median 49, IQR = 33-62) completed our survey. When asked, 'Do you know what ____ is'? participants expressed higher familiarity with insomnia (99%) and vertigo (87%) in comparison to dysphagia (25%) and ataxia (18%). From a list of 8 options, 99% and 94% participants selected the correct impairment for insomnia and vertigo respectively, compared with 44% correct for dysphagia and 22% for ataxia. Participants selected an appropriate healthcare provider for dysphagia 47% of the time compared with 74% for insomnia, 56% for vertigo and 36% for ataxia. When asked to identify up to 3 sequelae (from a list of 9), only 4% of participants were able to correctly identify all three for dysphagia, in comparison to 16% for ataxia, 27% for vertigo and 60% for insomnia. The Cosmos analysis revealed that while insomnia had the highest prevalence in 2023 (5.5% of patient encounters), dysphagia occurred much more frequently (2.4%) than vertigo (0.68%) and ataxia (0.24%). CONCLUSIONS:These discrepancies highlight a notable gap in public awareness between dysphagia and more recognized conditions of insomnia and vertigo, even though the prevalence of dysphagia is higher than vertigo. Increasing public awareness of dysphagia is vital for early intervention, increasing quality of life, and advocating for equitable access to healthcare resources.