Faculty Bibliography

Animal communication sounds exhibit complex temporal structure due to the amplitude fluctuations which comprise the sound envelope. In human speech, envelope modulations drive synchronized activity in auditory cortex, which correlates strongly with comprehension (Giraud and Poeppel, 2012; Peelle and Davis, 2012; Haegens and Zion Golumbic, 2018). Studies of envelope coding in single neurons, performed in non-human animals, have focused on periodic amplitude modulation (AM) stimuli and use response metrics that average neural activity over time. In this study, we sought to bridge these fields. Specifically, we looked directly at the temporal relationship between stimulus envelope and spiking, and we assessed whether the apparent diversity across neurons' AM responses contributes to the population representation of speech-like sound envelopes. We gathered responses from single neurons to vocoded speech stimuli and compared them to sinusoidal AM responses in auditory cortex (AC) of alert, freely moving Mongolian gerbils of both sexes. While AC neurons displayed heterogeneous tuning to AM rate, their temporal dynamics were stereotyped. Preferred response phases accumulated near the onsets of sinusoidal AM periods for slower rates (<8 Hz), and an over-representation of amplitude edges was apparent in population responses to both sinusoidal AM and vocoded speech envelopes. Crucially, this encoding bias imparted a decoding benefit: a classifier could discriminate vocoded speech stimuli using summed population activity, while higher frequency modulations required a more sophisticated decoder that tracked spiking responses from individual cells. Together, our results imply that the envelope structure relevant to parsing an acoustic stream could be read-out from a distributed, redundant population code.SIGNIFICANCE STATEMENT:Animal communication sounds have rich temporal structure and are often produced in extended sequences, including the syllabic structure of human speech. Although the auditory cortex is known to play a crucial role in representing speech syllables, the contribution of individual neurons remains uncertain. Here, we characterized the representations of both simple, amplitude-modulated sounds and complex, speech-like stimuli for a broad population of cortical neurons, and we found an overrepresentation of amplitude edges. Thus, a phasic, redundant code in auditory cortex can provide a mechanistic explanation for segmenting acoustic streams like human speech.

Purpose of Review: This review seeks to illuminate the challenges that arise in the use of steroids in the context of a performing voice, to review pharmacologic principles that can help to guide dosing regimens, to examine emerging science about the mechanistic action of glucocorticoids, and to provide a useful guide for clinicians who treat vocal performers. Recent Findings: Though perceptions and mythologies abound, most saliently (1) the incidence of vocal fold hemorrhage while taking oral steroids is extremely low; (2) appropriate dosing is likely to involve regimens that meet or exceed 30 mg oral Prednisone-equivalent daily to address edema acutely; (3) tapering after short courses may well be unnecessary. Summary: Steroids can be used safely and judiciously to treat vocal performers, guided by physical examination, sound clinical judgment, and a multidisciplinary approach to the individual needs of each unique voice and performer.

Head and neck squamous cell carcinoma (HNSCC) causes more severe pain and psychological stress than other types of cancer. Despite clinical evidence linking pain, stress, and cancer progression, the underlying relationship between pain and sympathetic neurotransmission in oral cancer is unknown. We found that human HNSCC tumors and mouse tumor tissue are innervated by peripheral sympathetic and sensory nerves. Moreover, [beta]-adrenergic 1 and 2 receptors ([beta]-AR) are overexpressed in human oral cancer cell lines, and norepinephrine treatment increased [beta]-AR2 protein expression as well as cancer cell proliferation in vitro. We have recently demonstrated that inhibition of tumor necrosis factor alpha (TNF[alpha]) signaling reduces oral cancer-induced nociceptive behavior. Norepinephrine-treated cancer cell lines secrete more TNF[alpha] which, when applied to tongue-innervating trigeminal neurons, evoked a larger Ca2+ transient; TNF-TNFR inhibitor blocked the increase in the evoked Ca2+ transient. Using an orthotopic xenograft oral cancer model, we found that mice demonstrated significantly less orofacial cancer-induced nociceptive behavior during systemic [beta]-adrenergic inhibitory treatment with propranolol. Furthermore, chemical sympathectomy via guanethidine led to a significant reduction in tumor size and nociceptive behavior. We infer from these results that sympathetic signaling modulates oral cancer pain via TNF[alpha] secretion and tumorigenesis. Further investigation of the role of neuro-cancer communication in cancer progression and pain is warranted.

Background: Survivors of oral cavity and oropharyngeal cancer frequently experience difficulties in swallowing; tasting; speaking; chewing; and maintaining comfortable movements of the head, neck, and shoulder. Engagement in regular self-care can reduce further loss of function and mitigate late effects. Despite the substantial self-care requirements, there are no empirically based interventions to enhance the skills and confidence of these survivors in managing their ongoing care. Objective: The aim of this study is to describe the rationale and methodology for a randomized controlled trial evaluating Empowered Survivor (ES) versus Springboard Beyond Cancer, a general web-based program for cancer survivors, on self-efficacy in managing care, preparedness for managing survivorship, and health-related quality of life (QOL). Methods: This study will recruit a total of 600 individuals who were diagnosed with oral cavity or oropharyngeal cancer in the past 3 years and are currently cancer free primarily from state cancer registries; these individuals will be randomly assigned to either the ES or Springboard Beyond Cancer condition. The participants complete measures of self-efficacy in managing care, preparedness for survivorship, health-related QOL, and engagement in oral self-examination and head and neck strengthening and flexibility exercises at baseline and 2 and 6 months after baseline. The primary aim of this study is to evaluate the impact of ES versus Springboard Beyond Cancer on self-efficacy, preparedness, and health-related QOL. The secondary aim is to examine the mediators and moderators of ES"™s impact on self-efficacy in managing care, preparedness, and health-related QOL at 6 months. The exploratory aim is to conduct a process evaluation of ES to identify potential oncology or community settings for future implementation. Results: Multilevel modeling will be used to examine whether there are significant differences between the ES and Springboard Beyond Cancer interventions over time. Mediational models will evaluate the indirect effects of ES on outcomes. Quantitative analyses will evaluate the predictors of ES use, and qualitative analyses will evaluate the preferred timing and settings for the implementation of ES. Conclusions: This randomized controlled trial evaluates a completely web-based intervention, ES, versus a general web-based program for cancer survivors, Springboard Beyond Cancer, on self-efficacy in managing care, preparedness for managing survivorship, and health-related QOL and identifies the putative mediators and moderators of the intervention"™s effects. If an effect on the primary outcomes is illustrated, the next step could be an implementation trial to evaluate the intervention"™s uptake in and impact on an oncology care setting or nonprofit organizations.

Objective: We conducted a qualitative study of patients"™ perspectives on dry mouth outcomes to explore their personal experiences and investigate which outcomes are most important to them. This work was part of the WONDER initiative (World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research) exploring Core Outcome Measures in Effectiveness Trials. Study Design: Using a study-specific topic guide, we conducted digitally recorded, semi-structured interviews of focus groups of patients with dry mouth secondary to Sjogren syndrome and head and neck radiotherapy. We conducted interviews until data saturation had been achieved and evaluated all transcripts for accuracy before we anonymized the data. Results: Two focus groups consisting of 4 participants per group identified 4 distinct themes: (1) impact on oral health and function, (2) social isolation and withdrawal, (3) frustration with dry mouth management, and (4) limited knowledge of the medical community and lack of understanding of family and friends. Conclusions: The diversity of self-reported outcomes and the complexity of patient perceptions identified in our work may represent additional barriers to successful dry mouth management that should be considered in the design of future clinical trials.

STUDY OBJECTIVES:To examine children with Down syndrome with residual obstructive sleep apnea (OSA) to determine if they are more likely to have positional OSA. METHODS:A retrospective chart review of children with Down syndrome who underwent adenotonsillectomy at a single tertiary children's hospital was conducted. Children with Down syndrome who had a postoperative polysomnogram with obstructive apnea-hypopnea index (OAHI) > 1 event/h, following adenotonsillectomy with at least 60 minutes of total sleep time were included. Patients were categorized as mixed sleep (presence of ≥ 30 minutes of both nonsupine and supine sleep), nonsupine sleep, and supine sleep. Positional OSA was defined as an overall OAHI > 1 event/h and a supine OAHI to nonsupine OAHI ratio of ≥ 2. Group differences are tested via Kruskal-Wallis test for continuous variables and Fisher's exact tests for categorical. RESULTS:= .002). Sixty (46%) of the mixed-sleep individuals had positional OSA, of which 29 (48%) had moderate/severe OSA. Sleeping off their backs converted 14 (48%) of these 29 children from moderate/severe OSA to mild OSA. CONCLUSIONS:Sleep physicians and otolaryngologists should be cognizant that the OAHI may be an underestimate if it does not include supine sleep. Positional therapy is a potential treatment option for children with residual OSA following adenotonsillectomy and warrants further investigation. CITATION:. 2023;19(1):171-177.