Faculty Bibliography

Background Tracheobronchopathia osteochondroplastica is a rare benign and often indolent disease. We report the first case of tracheobronchopathia osteochondroplastica (TBO) presenting as acute hypercarbic respiratory failure due to superimposed subglottic submucosal abscess. Case Report A 27-year-old man presented to the emergency department in respiratory distress that required mechanical ventilation for acute hypercarbic respiratory failure. Upon extubation the next day, stridor was elicited with ambulation. Spirometry revealed fixed upper airway obstruction. Neck imaging showed a 2.8x2.0x4.0 cm partially calcified subglottic mass with cystic and solid component obstructing 75% of the airway. Surgical exploration revealed purulent drainage upon elevation of the thyroid isthmus and an anterolateral cricoid wall defect in communication with a subglottic submucosal cavity. Microbiology was negative for bacteria or fungi. Pathology showed chondro-osseous metaplasia compatible with tracheobronchopathia osteochondroplastica (TBO). The patient received a course of antibiotics and prophylactic tracheostomy. Since tracheostomy removal 3 days later, the patient remains asymptomatic. Conclusions Tracheobronchopathia osteochondroplastica is a rare disease with usually benign clinical course and incidental diagnosis. It may present as acute hypercarbic respiratory failure when subglottic infection is superimposed.

In the zebra finch, singing behavior is driven by a sequence of bursts within premotor neurons located in the forebrain nucleus HVC (proper name). In addition to these excitatory projection neurons, HVC also contains inhibitory interneurons with a role in premotor patterning that is unclear. Here, we used a range of electrophysiological and behavioral observations to test previously described models suggesting discrete functional roles for inhibitory interneurons in song production. We show that single HVC premotor neuron bursts are sufficient to drive structured activity within the interneuron network because of pervasive and facilitating synaptic connections. We characterize interneuron activity during singing and describe reliable pauses in the firing of those neurons. We then demonstrate that these gaps in inhibition are likely to be necessary for driving normal bursting behavior in HVC premotor neurons and suggest that structured inhibition and excitation may be a general mechanism enabling sequence generation in other circuits.

Kikuchi-Fujimoto disease (KFD) is an unusual cause of lymphadenopathy and fever. Pregnancy associated with KFD presents as a diagnostic dilemma for clinicians. The diagnosis can be confirmed with invasive biopsies or non-invasive gene analysis. We report a case of a 24-year-old woman at 18 weeks' gestation with a neck lump and histologically confirmed KFD.

Sensory feedback is crucial for learning and performing many behaviors, but its role in the execution of complex motor sequences is poorly understood. To address this, we consider the forebrain nucleus HVC in the songbird, which contains the premotor circuitry for song production and receives multiple convergent sensory inputs. During singing, projection neurons within HVC exhibit precisely timed synaptic events that may represent the ongoing motor program or song-related sensory feedback. To distinguish between these possibilities, we recorded the membrane potential from identified HVC projection neurons in singing zebra finches. External auditory perturbations during song production did not affect synaptic inputs in these neurons. Furthermore, the systematic removal of three sensory feedback streams (auditory, proprioceptive, and vagal) did not alter the frequency or temporal precision of synaptic activity observed. These findings support a motor origin for song-related synaptic events and suggest an updated circuit model for generating behavioral sequences.

One challenge facing postlingually deafened cochlear implant (CI) users is the frequency mismatch between the incoming acoustic signal and the characteristic frequency of the electrically stimulated neurons. Current CI will require extensive effort in fine tuning to help users to adapt to this mismatch. A recent work [1] attempts to address this issue using a closed- loop CI system with evoked potentials as feedback. However, the stimulus artifact produced by CI and the limitation of subcortical responses in assessing speech perception are yet to resolve. In this paper we present our proposed cortical auditory evoked potential (AEP) evolved from a study [2] that addresses this mismatch. We describe the background then the experiments involved in the development of the AEP with recordings from 3 normal hearing (NH) listeners and 2 CI users. We also discuss how the AEP could be used in a closed- loop CI system.

Importance: A new diagnosis of adult-onset recurrent respiratory papillomatosis (AO-RRP) prompts many questions related to disease acquisition, course, and transmission. Recent attention to the human papillomavirus (HPV), along with emerging data on AO-RRP, provides a foundation for patient counseling. Objective: To provide a framework for these discussions, including an overview of the current literature on HPV-mediated disease across organs. Evidence Review: The peer-reviewed literature was culled to provide a comprehensive review encompassing AO-RRP and anogenital papilloma, as well as general HPV virology and pathophysiology. PubMed and Google Scholar databases were searched from 1975 to July 2014. Findings: Most HPV infections in healthy adults are cleared within 2 years without clinical significance. Adult-onset RRP is a rare manifestation of HPV and may be homologous to anogenital HPV, which is highly transmissible between sexual partners. Horizontal transmission of AO-RRP has not been characterized. Our laboratory, however, recently found that nearly 100% of patients with AO-RRP had concurrent oral cavity HPV infection. Historically, an increased number of oral sex partners was thought to be associated with AO-RRP, but recent data from our group did not corroborate this finding. Recent data also question the dogma that smoking and laryngopharyngeal reflux play a role in recidivistic disease. Management of AO-RRP is often symptom based and includes lesion excision or ablation with adjuvant therapies including cidofovir for refractory cases. Conclusions and Relevance: Recurrent respiratory papillomatosis may be related to a new or latent HPV infection, potentially obtained at birth, and the mechanism(s) underlying the progression from HPV infection to RRP remains unknown. Recommendations with regard to sexual practices in patients with AO-RRP cannot be made at this time. Unlike human immunodeficiency virus, patients with AO-RRP are not obligated to discuss infection status with partners. Despite the nebulous nature of the disease, clinicians should be a resource to discuss the current state of the literature with both the patient and partner.

To make sense of our ever-changing world, our brains search out patterns. This drive can be so strong that the brain imposes patterns when there are none. The opposite can also occur: The brain can overlook patterns because they do not conform to expectations. In this study, we examined this neural sensitivity to patterns within the auditory brainstem, an evolutionarily ancient part of the brain that can be fine-tuned by experience and is integral to an array of cognitive functions. We have recently shown that this auditory hub is sensitive to patterns embedded within a novel sound stream, and we established a link between neural sensitivity and behavioral indices of learning [Skoe, E., Krizman, J., Spitzer, E., & Kraus, N. The auditory brainstem is a barometer of rapid auditory learning. Neuroscience, 243, 104-114, 2013]. We now ask whether this sensitivity to stimulus statistics is biased by prior experience and the expectations arising from this experience. To address this question, we recorded complex auditory brainstem responses (cABRs) to two patterned sound sequences formed from a set of eight repeating tones. For both patterned sequences, the eight tones were presented such that the transitional probability (TP) between neighboring tones was either 33% (low predictability) or 100% (high predictability). Although both sequences were novel to the healthy young adult listener and had similar TP distributions, one was perceived to be more musical than the other. For the more musical sequence, participants performed above chance when tested on their recognition of the most predictable two-tone combinations within the sequence (TP of 100%); in this case, the cABR differed from a baseline condition where the sound sequence had no predictable structure. In contrast, for the less musical sequence, learning was at chance, suggesting that listeners were "deaf" to the highly predictable repeating two-tone combinations in the sequence. For this condition, the cABR also did not differ from baseline. From this, we posit that the brainstem acts as a Bayesian sound processor, such that it factors in prior knowledge about the environment to index the probability of particular events within ever-changing sensory conditions.