Faculty Bibliography

OBJECTIVES/OBJECTIVE:The auditory experience of early deafened pediatric cochlear implant (CI) users is different from that of postlingually deafened adult CI users due to disparities in the developing auditory system. It is therefore expected that the auditory psychophysical capabilities between these two groups would differ. In this study, temporal resolving ability was investigated using a temporal modulation detection task to compare the performance outcomes between these two groups. DESIGN/METHODS:The minimum detectable modulation depth of amplitude modulated broadband noise at 100 Hz was measured for 11 early deafened children with a CI and 16 postlingually deafened adult CI users. RESULTS:Amplitude modulation detection thresholds were significantly lower (i.e., better) for the pediatric CI users than for the adult CI users. Within each group, modulation detection thresholds were not significantly associated with chronologic age, age at implantation, or years of CI experience. CONCLUSIONS:Early implanted children whose auditory systems develop in response to electric stimulation demonstrate better temporal resolving abilities than postlingually deafened adult CI users. This finding provides evidence to suggest that early implanted children might benefit from sound coding strategies emphasizing temporal information.

This article is a part of the "Do you know your guidelines" series by the Education Committee of the American Head and Neck Society. The aim is to summarize the core principles outlined by the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines^® ) on management of malnutrition in patients with head and neck cancer. We outline the current recommendations from the National Comprehensive Cancer Network^® (NCCN^® ) for the screening and management of malnutrition, including indications for nutritional supplementation and placement of a nasogastric or gastrostomy tube. We also include a brief review of the available literature on additional screening tools, alternative guidelines, as well as an update on the emerging data surrounding the use of immune-enhancing nutrition.

BACKGROUND:Measurement of the angular depth of insertion (aDOI) of cochlear implant electrode arrays has numerous clinical and research applications. Plain-film radiographs are easily obtained intraoperatively and have been described as a means to calculate aDOI. CT imaging with 3D reformatting can also be used for this measurement, but is less conveniently obtained and requires higher radiation doses, a particular concern in pediatrics. The extent to which plain-film and 3D CT image-based measurements are representative of the true position of the electrode within the cochlea is unknown. METHODS:Cochlear implantation was performed on 10 cadaveric temporal bones. Five bones were implanted with perimodiolar electrodes (Contour Advance TM, Cochlear, Sydney, Australia) and five were implanted with lateral wall electrodes (Slim Straight, Cochlear). The insertion depths of the electrodes were varied. Each bone was imaged with a radiograph and CT. aDOI was measured for each bone in each imaging modality by a neurotologist and a neuroradiologist. To obtain a 'gold standard' estimate of aDOI, the implanted temporal bones were embedded in an epoxy resin and methodically sectioned at 100 μm intervals; histologic images were captured at each interval. A 3D stack of the images was compounded, and a MATLAB script used to calculate aDOI of the most apical electrode. Measurements in the three modalities (radiograph, CT, and histology) were then compared. RESULTS:The average aDOI across all bones was similar for all modalities: 423° for radiographs, 425° for CT scans, and 427° for histology, indicating that neither imaging modality resulted in large systematic errors. Using the histology-measured angles as a reference, the average error for CT-based measures (regardless of whether the error was in the positive or negative direction) was 12°, and that for radiograph-based measures was 15°. This small difference (12 vs 15° error) was not statistically significant. CONCLUSION/CONCLUSIONS:Based on this cadaveric temporal bone model, both radiographs and CTs can provide reasonably accurate aDOI measurements. In this small sample, and as expected, the CT-based estimates were more accurate than the radiograph-based measurements. However, the difference was small and not statistically significant. Thus, the use of plain radiographs to calculate aDOI seems judicious whenever it is desired to prevent unnecessary radiation exposure and expense.

OBJECTIVE:To survey patients following sinonasal surgery regarding postoperative pain and opioid use. STUDY DESIGN:Patients were surveyed for 4 days following sinus and/or nasal surgery regarding their pain level and use of prescribed opioids. SETTING:Four academic medical centers and 1 private practice institution. SUBJECTS:Consecutive adult patients undergoing sinonasal surgery. RESULTS:= 0.002, P = .48). No significant difference in postoperative pain or opioid consumption was seen with respect to age, sex, specific procedures performed, postoperative steroids, or smoking history. Current smokers reported higher average pain than nonsmokers ( P < .001) and also required more postoperative opioids ( P = .02). CONCLUSIONS:An evidence-based approach to postoperative pain control following sinonasal surgery that reduces the number of unused and potentially diverted opioids is needed. The current study suggests that 15 combination oxycodone (5-mg) and acetaminophen (325-mg) tablets provide sufficient pain control for 90% of patients in the immediate postoperative period following sinonasal surgery, irrespective of the specific procedures performed, use of acetaminophen, or use of systemic steroids. Smoking status may help surgeons predict which patients will require larger opioid prescriptions.

OBJECTIVE:Examine the relationship between duration of unilateral deafness and speech perception outcomes after cochlear implantation in adults with single-sided deafness. METHODS:A systematic review of PubMed articles containing individual speech perception and duration of deafness data from single-sided deaf adults. Studies were selected for detailed review and duration of deafness and speech perception outcomes were extracted, with speech scores reported as percent correct. A linear regression as a function of study and length of deafness was performed. RESULTS:A statistically significant negative effect of duration of unilateral deafness on speech perception was found, but there was substantial uncertainty regarding the strength of the effect. DISCUSSION/CONCLUSIONS:Existing data make it difficult to either support or reject a hard 5- or 10-year unilateral auditory deprivation limit on cochlear implant (CI) candidacy for patients with single-sided deafness. This is because the totality of available data are consistent with a very small effect, perhaps negligible in practical terms, and just as consistent with a very large effect. Regardless of effect size, the present results have important basic implications. They suggest that unilateral sound deprivation may have a deleterious effect on auditory processing even though more central parts of the auditory system have continued to receive input from a contralateral normal ear. CONCLUSIONS:Speech perception scores in SSD patients are negatively correlated with duration of deafness, but the limited amount of data from cochlear implant users with long-term single-sided deafness leads to substantial uncertainly, which in turn precludes any strong clinical recommendations. Further study of SSD CI users with long-term deafness will be necessary to generate evidence-based guidelines for implantation criteria in this population.

OBJECTIVES/OBJECTIVE:To examine the correlation between pharyngeal residue severity and clearance to penetration/aspiration on fiber-optic endoscopic examination of swallowing (FEES). DESIGN/METHODS:Retrospective cohort. SETTING/METHODS:Kaplan Medical Center dysphagia clinic. PARTICIPANTS/METHODS:Patients (N=110) visiting a dysphagia clinic between 2014 and 2016 undergoing FEES. INTERVENTIONS/METHODS:FEES were scored for penetration/aspiration with the Penetration Aspiration Scale (PAS), for residue severity using the Yale Pharyngeal Residue Severity Rating Scale (YPR-SRS). The numbers of swallows required to clear the pharynx were recorded. The first and the worst bolus challenges for each consistency (liquid, purée, solid) were analyzed. MAIN OUTCOME MEASURES/METHODS:YPR-SRS and number of clearing swallows were correlated with the PAS of the same bolus challenge. RESULTS:The study population's mean age was 67±13.4 years; 54% were men (n=58). A significant correlation was found between the YPR-SRS and the PAS for all consistencies tested, in each anatomical site (vallecula or pyriform sinus) and for both the first and worst bolus challenges (P<.001 for all). The correlation of residue with aspiration was stronger when vallecula and pyriform sinuses scores were summated (Pearson product-moment correlation coefficient=0.573/0.631/0.446 for liquid/purée/solid for worst bolus challenge). Incorporating the number of clearing swallows to the YPR-SRS strengthened the correlation with PAS. CONCLUSIONS:Residue severity and clearance correlate with penetration/aspiration on FEES. The YPR-SRS can be applied to standardize description of residue in FEES and to aid in dysphagia evaluation.

Bone cancer metastasis is extremely painful and decreases the quality of life of the affected patients. Available pharmacological treatments are not able to sufficiently ameliorate the pain and as cancer patients are living longer new treatments for pain management are needed. Decitabine (5-aza-2'-deoxycytidine), a DNA methyltransferases inhibitor, has analgesic properties in pre-clinical models of post-surgical and soft tissue oral cancer pain by inducing an up-regulation of endogenous opioids. In this study, we report that daily treatment with decitabine (2µg/g, i.p.) attenuated nociceptive behavior in the 4T1-luc2 mouse model of bone cancer pain. We hypothesized that the analgesic mechanism of decitabine involved activation of the endogenous opioid system through demethylation and reexpression of the transcriptionally silenced endothelin B receptor gene, Ednrb. Indeed, Ednrb was hypermethylated and transcriptionally silenced in the mouse model of bone cancer pain. We demonstrated that expression of Ednrb in the cancer cells lead to release of β-endorphin in the cell supernatant which reduced the number of responsive DRG neurons in an opioid-dependent manner. Our study supports a role of demethylating drugs, such as decitabine, as unique pharmacological agents targeting the pain in the cancer microenvironment.

Introduction: Vagus nerve stimulation is currently used as a medical treatment for those suffering from severe epilepsy or depression, but the mechanisms underlying vagus nerve stimulation are poorly understood. The vagus nerve helps connect essentially all peripheral organs to the central nervous system, sending afferents to the nucleus tractus solitarius. Recent studies indicate that vagus nerve stimulation can produce long-lasting plasticity in the cerebral cortex, leading to improved sensory processing and recovery of motor behavior after stroke (Boreland et al, Brain Stimul (2016). An understanding of the circuit mechanisms by which vagus nerve stimulation can produce these results would be important for enhancing behavioral outcomes and developing less invasive or non-invasive neuromodulatory therapeutic techniques. Method(s): Studies in mice provide an opportunity for monitoring and manipulating various aspects of neural circuits involved in behavior. One difficulty in the mouse model is the lack of vagus nerve cuff electrodes given the small size of the mouse vagus nerve. We first built a novel vagus nerve cuff electrode for mice and demonstrated reliable low-impedance recordings and stimulation during behavior in mice chronically implanted for months. Two-photon imaging of the auditory cortex was used to track neural responses to tones paired with vagus nerve stimulation. Animals are then trained on either a paired go/no-go or two-alternative forced choice auditory detection and recognition task (Martins and Froemke, Nat Neurosci 2015; Kuchibhotla et al. Nat Neurosci 2017). Result(s): Stimulation of the vagus nerve was calibrated to transiently reduce respiration without affecting other physiological processes (e.g., heart rate). Using two-photon imaging, we found that pairing target tones with vagus nerve stimulation for five minutes led to a short-term enhancement of sensory responses in the mouse auditory cortex. After several days of these brief 5-minute pairing sessions, long-term plasticity was observed with increases in representation of the target tone for at least days thereafter. Conclusion(s): These changes are reminiscent of the effects of basal forebrain stimulation (Froemke et al. Nature 2007) and we are now investigating how vagus nerve stimulation might lead to direct or indirect activation of central modulatory systems to improve plasticity and behavior in mice.

Introduction: The mammalian enteric nervous system (ENS) regulates intestinal function in response to luminal changes in nutrients and microbiota. The ENS also modulates immune cells to control microbial homeostasis and fight infections. Enteric neurons signal to the brain via the vagus nerve, providing a mechanism by which microbiota can influence neural activity and behavior at homeostasis or during infections with gut pathogens. However, little is known about the relation between vagus nerve activity and 'sickness behaviors' such as decreased attention, increased irritability and depression, and decreased interest and energy. Here we aimed to record vagus nerve responses in behaving animals towards understanding this gut-brain signaling connection in sickness behavior. Method(s): Custom nerve cuff electrodes were used to monitor vagus nerve activity of wild-type male mice. Cuffs were made with 0.2 mm micro-renathane tubing to surround the upper branch of the sensory vagus nerve and connected to socket gold pins and medwire. Chronic nerve cuffs were implanted in mice aged 6-12 weeks. Surgery consisted of securing gold pins to the cranial vertex and connecting electrodes to the vagus nerve in the neck, around which the cuff was placed. The grounding wire was secured near the cuff. One to two weeks post-surgery, each mouse underwent sickness induction via lipopolysaccharide (LPS) injection. LPS solution was formulated with 9.5/g muL of 0.9% saline solution and 0.5/g muL of pure LPS via intraperitoneal injection. Electrophysiological activity of the vagus nerve was recorded together with video monitoring of behavior, prior to injection to first establish a baseline, and post-injection activity was recorded for up to 24 hours. Sickness behavior was ethogrammed and neural activity analyzed in each animal. Result(s): LPS injection led to reduction of several different behaviors including overall motion in the homecage for hours afterwards. Analysis of simultaneously-recorded vagus activity is ongoing. Conclusion(s): We here describe an integrated system that combines long-term videography and behavioral analysis with recordings of the peripheral nerve activity using a custom chronic nerve cuff for the mouse vagus. Using this system, we have begun to relate neural activity in the sensory vagus to physiological state and behavioral changes in mice for the first time.

Purpose Although vocal training is often purported to restore and rebalance laryngeal muscle function, little is known about the direct effects of vocal training on the laryngeal muscles themselves. Consequently, parameters of vocal exercise dose, such as training duration and intensity, have not been well defined. The goal of this study was to use a behavioral animal model to determine the effects of short- and long-term ultrasonic vocalization (USV) training on USV acoustics, thyroarytenoid (TA) muscle neuromuscular junctions (NMJs), and TA muscle fiber size in adult rats. Method Twenty-four young adult male Long-Evans rats were divided into 3 groups (untrained control, 4-week training, and 8-week training). Baseline and posttraining USVs were recorded and acoustically analyzed for fundamental frequency, frequency bandwidth, amplitude, and duration. Presynaptic and postsynaptic NMJ morphological features and muscle fiber size were measured in the TA. Results USV training had no effect on USV acoustics. Eight weeks of USV training, however, resulted in a lower NMJ motor endplate dispersion ratio, consistent with previous findings. USV training did not affect fiber size within the TA muscle. Conclusions This study demonstrated that 8 weeks of USV training can induce peripheral neural adaptations in the NMJ of the TA muscle in young rats. The observed adaptations suggest that vocal training is consistent with endurance-type exercise, but the adaptations occur on a longer time scale than similar adaptations in the limb muscles.