Faculty Bibliography

Alston's singing mice (Scotinomys teguina) are highly vocal Central American rodents that produce structured "songs" (duration: 5-10 s),¹

Tumors of the paranasal sinus and nasal cavity (PNS/NC) are rare and exhibit diverse histology, anatomic subsite, and malignant potential. Early-stage disease is typically managed with surgery, and locally advanced disease is treated with a combination of surgery, radiotherapy, and chemotherapy. Clinical decision-making is commonly guided by limited retrospective evidence. To address this limitation, we performed a systematic review to inform evidence-based consensus for the management of common clinical scenarios, including the potential roles of radiation and systemic therapy to promote structural preservation, elective neck management, and radiation technique considerations. A librarian-mediated literature search identified 39 studies of adult patients with PNS/NC tumors treated with curative intent that met the study inclusion criteria. Search results were reported using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) methodology. A modified-Delphi process was used to guide consensus for the appropriate use of various management strategies. Strong consensus existed for the appropriateness of primary surgery for early-stage disease, approaches to locally advanced disease with minimal periorbital fat invasion, and the use of induction chemotherapy with response-directed local therapy. Consensus regarding nodal treatment and the use of proton therapy in the adjuvant setting was less robust. The rarity and diversity of PNS/NC tumors limit randomized phase III trials to guide management. As such, this systematic review and appropriate-use consensus statements provide clinical guidance for the management of this challenging disease spectrum.

OBJECTIVE:Observe if metal artifact reduction (MAR) techniques applied to magnetic resonance imaging (MRI) performed on patients with cochlear implants (CI) or auditory brainstem implants (ABI) improves image quality. STUDY DESIGN/METHODS:Retrospective review. SETTING/METHODS:Tertiary care center. PATIENTS/METHODS:Patients with auditory implants who underwent clinical MRI before and after the application of MAR techniques previously described. INTERVENTIONS/METHODS:From September 2022 to March 2023, patients who underwent brain or internal auditory canal (IAC) MRI with and without MAR were identified. Sequences included T1 and T2 weighted with turbo-spin-echo (TSE) correction and fluid-attenuation inversion recovery (FLAIR). Images were analyzed for visualization of intracranial structures by two neuroradiologists. MAIN OUTCOME MEASURES/METHODS:Visibility of 14 structures graded on a four-point Likert scale. Average scores per structure and sequence were compared using paired two-tailed t-tests and change in mode score. RESULTS:Ten patients underwent pre- and post-MAR MRI. Six had a unilateral CI, three had a unilateral ABI, and one had an ABI and CI. Three patients had four devices with the internal magnet removed for both scans. All structures had significantly improved visibility on post-MAR scan except ipsilateral parietal and occipital lobes and contralateral inner ear. Mode score increased from 2 to 4 for the ipsilateral occipital lobe and from 3 to 4 for the ipsilateral semicircular canals, brainstem, and cerebellar peduncles. Significant improvement was seen in all sequences except for ipsilateral structures on T1w axial precontrast and contralateral structures on T1w coronal postcontrast. ABIs did not improve as much as CIs because they scored better on the pre-MAR scan. CONCLUSIONS:MAR techniques improve image quality for patients with MRI-compatible implants with magnets. Benefits may be more evident in CIs than ABIs.

BACKGROUND:Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neuroendocrine tumors. PitNETs can be challenging to classify, and current recommendations include a large immunohistochemical panel to differentiate among 14 WHO-recognized categories. METHODS:In this study, we analyzed clinical, immunohistochemical and DNA methylation data of 118 PitNETs to develop a clinico-molecular approach to classifying PitNETs and identify epigenetic classes. RESULTS:CNS DNA methylation classifier has an excellent performance in recognizing PitNETs and distinguishing the three lineages when the calibrated score is ≥0.3. Unsupervised DNA methylation analysis separated PitNETs into two major clusters. The first was composed of silent gonadotrophs, which form a biologically distinct group of PitNETs characterized by clinical silencing, weak hormonal expression on immunohistochemistry, and simple copy number profile. The second major cluster was composed of corticotrophs and Pit1 lineage PitNETs, which could be further classified using DNA methylation into distinct subclusters that corresponded to clinically functioning and silent tumors and are consistent with transcription factor expression. Analysis of promoter methylation patterns correlated with lineage for corticotrophs and Pit1 lineage subtypes. However, the gonadotrophic genes did not show a distinct promoter methylation pattern in gonadotroph tumors compared to other lineages. Promoter of the NR5A1 gene, which encodes SF1, was hypermethylated across all PitNETs clinical and molecular subtypes including gonadotrophs with strong SF1 protein expression indicating alternative epigenetic regulation. CONCLUSION/CONCLUSIONS:Our findings suggest that classification of PitNETs may benefit from DNA methylation for clinicopathological stratification.

Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells - the output neurons of the cerebellar cortex - as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

OBJECTIVE:This study aims to describe current practices among otolaryngology-trained microtia surgeons in the United States. STUDY DESIGN/METHODS:Survey. SETTING/METHODS:A tertiary care center. METHODS:A 22-question anonymous digital survey of practice patterns and surgical methods was distributed to all members of the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS) and the American Society of Pediatric Otolaryngology (ASPO). Responses were analyzed using descriptive statistics and linear regression models. RESULTS:Of 1730 eligible members, 83 (4.8%) responses were collected. Forty-three (51.8%) were AAFPRS members, 39 (47.0%) were ASPO members, and 1 (1.2%) reported dual membership. Respondents had multiple practice settings, were at different stages in their experience, and were well-distributed geographically. Forty (48.2%) don't perform microtia repair and half (52.5%) refer to an FPRS-trained colleague. Among microtia surgeons, most (N = 30, 69.8%) received fellowship training. Autologous reconstruction was the most popular method for training and practice; however, most perform multiple methods (N = 33, 76.7%). Autologous rib training was positively correlated with experience of >20 years. Those with combined autologous/alloplastic practice were more frequently trained by PO fellowship. Surgical site infection was the most frequent complication and was seen more often by those trained via residency alone (OR 12.8, P < .05). Those who trained in autologous rib alone were less likely to encounter postoperative graft exposure (OR 5.0, P < .05); however, they were more likely to encounter skin and soft tissue infection (OR 0.07, P < .05). CONCLUSION/CONCLUSIONS:Otolaryngology-trained microtia surgeons come from a variety of academic backgrounds and progress to varied practices. They are trained and practice both alloplastic and autologous repair methods, although autologous methods remain the most common.

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:The purpose of this study is to characterize patients who work professionally as musical performers and undergo potassium titanyl phosphate (KTP) laser ablation of vocal fold lesions in the outpatient setting. METHODS:A retrospective chart review of patients who are vocal performers and underwent in-office KTP laser ablation of benign vocal fold lesions at a single academic institution between 2012 and 2023 was conducted. Demographics including occupation, were descriptively reviewed. Acoustic measures, including cepstral peak prominence (CPP) and mean fundamental frequency variance (F0CoV), were analyzed. Vocal fold vibratory amplitude and mucosal wave were evaluated on videostroboscopy utilizing the voice vibratory assessment with laryngeal imaging. Preablation and postablation outcome measures were compared via Wilcoxon signed rank and McNemar's test. RESULTS:26 patients who identified as singers successfully underwent single-treatment in-office KTP laser ablation of vocal fold polyps. Ten patients (38.5%) identified as professional performers, and all patients continued their occupation after ablation. 84.2% of patients had either complete recovery or mildly reduced mucosal wave and amplitude of the treated vocal fold following KTP laser ablation. Additionally, CPP vowel improved following in-office KTP laser ablation, and F0CoV decreased following the ablation. All patients were able to continue their occupation in the same capacity. CONCLUSION/CONCLUSIONS:In-office KTP ablation is a valuable, safe, and feasible intervention for professional performers with benign vocal fold polyps. This study provides insight into vocal outcomes in the largest cohort of professional performers with apt follow-up.

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.

The endoscopic transsphenoidal approach (ETSA) is a commonly used technique that allows for the minimally invasive removal of sellar and parasellar lesions. Augmented reality (AR) applications in ETSA are hypothesized to enhance intraoperative visualization by integrating a 3D-reconstructed model into the operative field. This study describes the workflow and surgical outcomes associated with the Endoscopic Surgical Navigation Advanced Platform (EndoSNAP, Surgical Theater, Cleveland, OH, USA), an AR platform designed for surgical planning and intraoperative navigation in ETSA for sellar and parasellar lesions. We analyzed a cohort of patients who underwent ETSA tumor resection using EndoSNAP. Preoperative MRI and CT scans were reconstructed and merged into a single 360° AR model using the Surgical Rehearsal Platform software. The model was then imported into EndoSNAP, which was integrated with the endoscope and neuronavigation system for real-time intraoperative use. Patient demographics, tumor characteristics, extent of resection (EOR), and endocrinologic and neurologic outcomes were recorded. Eighteen adult patients with newly diagnosed (83%) and recurrent (17%) tumors were included. Pathologies consisted of pituitary adenoma (72%), craniopharyngioma (11%), meningioma (11%), and chordoma (6%). Optic compression was present in 56% of patients, with preoperative visual deficits in 70% of them. Cavernous sinus invasion was observed in 17% of tumors. Preoperative hormonal excess and insufficiency were noted in 56% and 28% of cases, respectively. The mean preoperative tumor volume was 21.4 ± 17 cm³, which decreased to 0.4 ± 0.3 cm³ postoperatively. The mean EOR was 93.6 ± 3.6%. Postoperative complications included CSF leaks requiring surgical repair (17%), seizures related to pre-existing hemispheric trauma (6%), pulmonary embolism (6%), deep venous thrombosis (6%), and sinusitis (6%). These findings suggest that AR-enhanced visualization through EndoSNAP is a feasible and potentially beneficial adjunct in ETSA for sellar and parasellar tumor resection.