Department of Otolaryngology—Head and Neck Surgery Works
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Item Preschool Speech Intelligibility and Vocabulary Skills Predict Long-Term Speech and Language Outcomes Following Cochlear Implantation in Early Childhood(Taylor & Francis, 2014) Castellanos, Irina; Kronenberger, William G.; Beer, Jessica; Henning, Shirley C.; Colson, Bethany G.; Pisoni, David B.; Otolaryngology -- Head and Neck Surgery, School of MedicineSpeech and language measures during grade school predict adolescent speech-language outcomes in children who receive cochlear implants (CIs), but no research has examined whether speech and language functioning at even younger ages is predictive of long-term outcomes in this population. The purpose of this study was to examine whether early preschool measures of speech and language performance predict speech-language functioning in long-term users of CIs. Early measures of speech intelligibility and receptive vocabulary (obtained during preschool ages of 3-6 years) in a sample of 35 prelingually deaf, early-implanted children predicted speech perception, language, and verbal working memory skills up to 18 years later. Age of onset of deafness and age at implantation added additional variance to preschool speech intelligibility in predicting some long-term outcome scores, but the relationship between preschool speech-language skills and later speech-language outcomes was not significantly attenuated by the addition of these hearing history variables. These findings suggest that speech and language development during the preschool years is predictive of long-term speech and language functioning in early-implanted, prelingually deaf children. As a result, measures of speech-language functioning at preschool ages can be used to identify and adjust interventions for very young CI users who may be at long-term risk for suboptimal speech and language outcomes.Item Some Factors Underlying Individual Differences in Speech Recognition on PRESTO: A First Report(American Academy of Audiology, 2013) Tamati, Terrin N.; Gilbert, Jaimie L.; Pisoni, David B.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Previous studies investigating speech recognition in adverse listening conditions have found extensive variability among individual listeners. However, little is currently known about the core underlying factors that influence speech recognition abilities. Purpose: To investigate sensory, perceptual, and neurocognitive differences between good and poor listeners on the Perceptually Robust English Sentence Test Open-set (PRESTO), a new high-variability sentence recognition test under adverse listening conditions. Research design: Participants who fell in the upper quartile (HiPRESTO listeners) or lower quartile (LoPRESTO listeners) on key word recognition on sentences from PRESTO in multitalker babble completed a battery of behavioral tasks and self-report questionnaires designed to investigate real-world hearing difficulties, indexical processing skills, and neurocognitive abilities. Study sample: Young, normal-hearing adults (N = 40) from the Indiana University community participated in the current study. Data collection and analysis: Participants' assessment of their own real-world hearing difficulties was measured with a self-report questionnaire on situational hearing and hearing health history. Indexical processing skills were assessed using a talker discrimination task, a gender discrimination task, and a forced-choice regional dialect categorization task. Neurocognitive abilities were measured with the Auditory Digit Span Forward (verbal short-term memory) and Digit Span Backward (verbal working memory) tests, the Stroop Color and Word Test (attention/inhibition), the WordFam word familiarity test (vocabulary size), the Behavioral Rating Inventory of Executive Function-Adult Version (BRIEF-A) self-report questionnaire on executive function, and two performance subtests of the Wechsler Abbreviated Scale of Intelligence (WASI) Performance Intelligence Quotient (IQ; nonverbal intelligence). Scores on self-report questionnaires and behavioral tasks were tallied and analyzed by listener group (HiPRESTO and LoPRESTO). Results: The extreme groups did not differ overall on self-reported hearing difficulties in real-world listening environments. However, an item-by-item analysis of questions revealed that LoPRESTO listeners reported significantly greater difficulty understanding speakers in a public place. HiPRESTO listeners were significantly more accurate than LoPRESTO listeners at gender discrimination and regional dialect categorization, but they did not differ on talker discrimination accuracy or response time, or gender discrimination response time. HiPRESTO listeners also had longer forward and backward digit spans, higher word familiarity ratings on the WordFam test, and lower (better) scores for three individual items on the BRIEF-A questionnaire related to cognitive load. The two groups did not differ on the Stroop Color and Word Test or either of the WASI performance IQ subtests. Conclusions: HiPRESTO listeners and LoPRESTO listeners differed in indexical processing abilities, short-term and working memory capacity, vocabulary size, and some domains of executive functioning. These findings suggest that individual differences in the ability to encode and maintain highly detailed episodic information in speech may underlie the variability observed in speech recognition performance in adverse listening conditions using high-variability PRESTO sentences in multitalker babble.Item Age-related changes in prosodic features of maternal speech to prelingually deaf infants with cochlear implants(Wiley, 2013) Kondaurova, Maria V.; Bergeson, Tonya R.; Xu, Huipuing; Otolaryngology -- Head and Neck Surgery, School of MedicineThis study investigated prosodic and structural characteristics of infant-directed speech to hearing-impaired infants as they gain hearing experience with a cochlear implant over a 12-month period of time. Mothers were recorded during a play interaction with their HI infants (N = 27, mean age 18.4 months) at 3, 6, and 12 months post-implantation. Two separate control groups of mothers with age-matched normal-hearing infants (NH-AM) (N = 21, mean age 18.1 months) and hearing experience-matched normal-hearing infants (NH-EM) (N = 24, mean age 3.1 months) were recorded at three testing sessions. Mothers produced less exaggerated pitch characteristics, a larger number of syllables per utterance, and faster speaking rate when interacting with NH-AM as compared to HI infants. Mothers also produced more syllables and demonstrated a trend suggesting faster speaking rate in speech to NH-EM relative to HI infants. Age-related modifications included decreased pitch standard deviation and increased number of syllables in speech to NH-AM infants and increased number of syllables in speech to HI and NH-EM infants across the 12-month period. These results suggest that mothers are sensitive to the hearing status of their infants and modify characteristics of infant-direct speech over time.Item Feasibility of Using Inertial Measurement Units (IMUs) to Augment Cadaveric Temporal Training(Wiley, 2025) Wesson, Troy; Ambike, Satyajit; Patel, Radha; Yates, Charles; Nelson, Rick; Francis, Alexander; Burgin, Sarah; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: Insertional speed of cochlear implant electrode arrays (EA) during surgery is correlated with force. Low insertional speed, and therefore force, may allow for preservation of intracochlear structures leading to improved outcomes. Given the importance of low insertional speeds, we investigate the feasibility of using inertial sensors for kinematic analysis during EA insertion to augment otolaryngology-head and neck surgery training. Methods: Practicing otolaryngology surgeons were recruited and inertial measurement units (IMU; Metamotions+, MBIENTLAB Inc, San Jose, CA) consisting of accelerometers were used to measure hand speed during EA (Cochlear™Nucleus®CI522 cochlear implant with Slim Straight electrode, Cochlear Limited, Sydney, Australia) insertion into a cadaveric cochlea. A mixed regression model was utilized to determine differences in speed across trials within a surgeon. Results: A total of nine trials were performed by three surgeons. The highest mean ± SD speed obtained was 8.4 ± 1.7 mm/s, and the highest speed was 22.5 mm/s. Mean speed was not significantly different across trials within surgeons (p > 0.05). Discussion: IMUs are relatively inexpensive and relatively easy to use sensors that provide information on variables that may be of interest for otolaryngology resident training. The use of IMUs as part of advanced temporal training for cochlear electrode insertion can provide insight into hand speed, thereby allowing residents to train with specific regard to this variable. Future randomized-controlled trials can be carried out to determine whether IMUs are conducive to lower insertional speeds.Item Altered Tissue Specialized Pro-Resolving Mediators in Chronic Rhinosinusitis(Elsevier, 2021) Vickery, Thad W.; Armstrong, Michael; Kofonow, Jennifer M.; Robertson, Charles E.; Kroehl, Miranda E.; Reisdorph, Nichole A.; Ramakrishnan, Vijay R.; Frank, Daniel N.; Otolaryngology -- Head and Neck Surgery, School of MedicineCurrent literature implicates arachidonic acid-derived leukotrienes and prostaglandins in the pathogenesis of chronic rhinosinusitis. However, other omega-3 and omega-6 derived lipid mediators, such as specialized pro-resolving mediators (SPMs), may also be important in chronic inflammatory disorders of the upper airway. We hypothesize that SPMs differ among CRS subtypes compared to controls and in relation to sinonasal microbiota. Ethmoid sinus tissue and middle meatal swabs were collected from a convenience sample of 66 subjects, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. Resolvin D2 was elevated in both CRSwNP (p = 0.00076) and CRSsNP (p = 0.030) compared with non-CRS controls. Lipoxin A4 was significantly increased in CRSwNP compared with CRSsNP (p = 0.000033) and controls (p = 0.044). Cigarette smoking was associated with significantly lower concentrations of several 15-lipoxygenase metabolites including resolvin D1 (p = 0.0091) and resolvin D2 (p = 0.0097), compared with never-smokers. Several of the lipid compounds also correlated with components of the sinonasal mucosal microbiota, including bacterial pathogens such as Pseudomonas aeruginosa. These data suggest that dysfunctional lipid mediator pathways in CRS extend beyond the traditional descriptions of leukotrienes and prostaglandins and include SPMs. Furthermore, dysregulated SPM signaling may contribute to persistent inflammation and bacterial colonization in CRS.Item A Dysbiotic Microbiome Promotes Head and Neck Squamous Cell Carcinoma(Springer Nature, 2022) Frank, Daniel N.; Qiu, Yue; Cao, Yu; Zhang, Shuguang; Lu, Ling; Kofonow, Jennifer M.; Robertson, Charles E.; Liu, Yanqiu; Wang, Haibo; Levens, Cassandra L.; Kuhn, Kristi A.; Song, John; Ramakrishnan, Vijay R.; Lu, Shi-Long; Otolaryngology -- Head and Neck Surgery, School of MedicineRecent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.Item Word and Nonword Reading Efficiency in Postlingually Deafened Adult Cochlear Implant Users(Wolters Kluwer, 2021) Tamati, Terrin N.; Vasil, Kara J.; Kronenberger, William G.; Pisoni, David B.; Moberly, Aaron C.; Ray, Christin; Otolaryngology -- Head and Neck Surgery, School of MedicineHypothesis: This study tested the hypotheses that 1) experienced adult cochlear implants (CI) users demonstrate poorer reading efficiency relative to normal-hearing controls, 2) reading efficiency reflects basic, underlying neurocognitive skills, and 3) reading efficiency relates to speech recognition outcomes in CI users. Background: Weak phonological processing skills have been associated with poor speech recognition outcomes in postlingually deaf adult CI users. Phonological processing can be captured in nonauditory measures of reading efficiency, which may have wide use in patients with hearing loss. This study examined reading efficiency in adults CI users, and its relation to speech recognition outcomes. Methods: Forty-eight experienced, postlingually deaf adult CI users (ECIs) and 43 older age-matched peers with age-normal hearing (ONHs) completed the Test of Word Reading Efficiency (TOWRE-2), which measures word and nonword reading efficiency. Participants also completed a battery of nonauditory neurocognitive measures and auditory sentence recognition tasks. Results: ECIs and ONHs did not differ in word (ECIs: M = 78.2, SD = 11.4; ONHs: M = 83.3, SD = 10.2) or nonword reading efficiency (ECIs: M = 42.0, SD = 11.2; ONHs: M = 43.7, SD = 10.3). For ECIs, both scores were related to untimed word reading with moderate to strong effect sizes (r = 0.43-0.69), but demonstrated differing relations with other nonauditory neurocognitive measures with weak to moderate effect sizes (word: r = 0.11-0.44; nonword: r = (-)0.15 to (-)0.42). Word reading efficiency was moderately related to sentence recognition outcomes in ECIs (r = 0.36-0.40). Conclusion: Findings suggest that postlingually deaf adult CI users demonstrate neither impaired word nor nonword reading efficiency, and these measures reflect different underlying mechanisms involved in language processing. The relation between sentence recognition and word reading efficiency, a measure of lexical access speed, suggests that this measure may be useful for explaining outcome variability in adult CI users.Item Interaction of the C2C12 myotube contractions and glucose availability on transcriptome and extracellular vesicle microRNAs(American Physiological Society, 2024) Lautaoja-Kivipelto, Juulia H.; Karvinen, Sira; Korhonen, Tia-Marje; O’Connell, Thomas M.; Tiirola, Marja; Hulmi, Juha J.; Pekkala, Satu; Otolaryngology -- Head and Neck Surgery, School of MedicineExercise-like electrical pulse stimulation (EL-EPS) of myotubes mimics many key physiological changes induced by in vivo exercise. Besides enabling intracellular research, EL-EPS allows to study secreted factors, including muscle-specific microRNAs (myomiRs) carried in extracellular vesicles (EVs). These factors can participate in contraction-induced intercellular cross talk and may mediate the health benefits of exercise. However, the current knowledge of these responses, especially under variable nutritional conditions, is limited. We investigated the effects of EL-EPS on C2C12 myotube transcriptome in high- and low-glucose conditions by messenger RNA sequencing, while the expression of EV-carried miRNAs was analyzed by small RNA sequencing and RT-qPCR. We show that higher glucose availability augmented contraction-induced transcriptional changes and that the majority of the differentially expressed genes were upregulated. Furthermore, based on the pathway analyses, processes related to contractility and cytokine/inflammatory responses were upregulated. In addition, we report that EL-EPS increased packing of miR-1-3p into EVs independent of glucose availability. Together our findings suggest that in vitro EL-EPS is a usable tool not only to study contraction-induced intracellular mechanisms but also extracellular responses. The distinct transcriptional changes observed under variable nutritional conditions emphasize the importance of careful consideration of media composition in future exercise-mimicking studies. NEW & NOTEWORTHY: The present study examined for the first time the effects of exercise-like electrical pulse stimulation administered under distinct nutritional conditions on 1) the transcriptome of the C2C12 myotubes and 2) their media containing extracellular vesicle-carried microRNAs. We report that higher glucose availability augmented transcriptional responses related especially to contractility and cytokine/inflammatory pathways. Agreeing with in vivo studies, we show that the packing of exercise-responsive miR-1-3p was increased in the extracellular vesicles in response to myotube contractions.Item Impact of Adjuvant Interferon Therapy on Survival Outcomes for Cutaneous Melanoma With Parotid Involvement(Wiley, 2025) Kim, Erin; Raven, Sarah A.; Lenze, Nicholas R.; Farlow, Janice L.; McLean, Scott A.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjectives: To determine the relative 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) outcomes for adjuvant interferon therapy in the treatment of head and neck cutaneous melanoma (HNCM) with parotid gland involvement. Methods: A retrospective cohort study was conducted at a single tertiary care institution to analyze patients undergoing parotidectomy for cutaneous head and neck melanoma involving the parotid gland from 2000 to 2014. Time-to-event analyses were performed using Kaplan-Meier curves with log-rank p-values and Cox proportional hazards models. Results: The sample consisted of 82 patients who underwent surgical resection of stage III HNCM with parotid involvement. The mean follow-up was 67.8 months (SD 65) after diagnosis. Twenty-one patients received adjuvant interferon therapy, 12 patients received adjuvant radiation therapy, and 49 patients received no adjuvant therapy. Crude 5-year OS rates were 95.0% for interferon therapy, 33.3% for adjuvant RT, and 40.4% for no adjuvant therapy. Crude 5-year RFS rates were 75.2%, 19.5%, and 40.8% respectively. In the fully adjusted model, adjuvant interferon therapy was associated with improved 5-year OS compared to adjuvant RT (HR 0.10, 95% CI 0.011-0.837; p = 0.034). There was no significant association between adjuvant interferon therapy and 5-year RFS in the fully adjusted model. Conclusion: Adjuvant interferon therapy for surgically resected stage III cutaneous melanoma with parotid gland involvement may be associated with improved survival outcomes. These findings support the growing evidence for the use of immunotherapy in melanoma, and potentially a unique role for when melanoma involves the lymphatic-rich parotid gland.Item Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis(Wiley, 2024) Kaefer, Samuel L.; Zhang, Lujuan; Morrison, Rachel A.; Brookes, Sarah; Awonusi, Oluwaseyi; Shay, Elizabeth; Hoilett, Orlando S.; Anderson, Jennifer L.; Goergen, Craig J.; Voytik-Harbin, Sherry; Halum, Stacey; Otolaryngology -- Head and Neck Surgery, School of MedicineObjectives: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury. Methods: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology. Results: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR. Conclusions: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction.