Faculty Bibliography

OBJECTIVE:In this study, the authors aimed to clarify the relationship between hearing loss and tumor volumetric growth rates in patients with untreated vestibular schwannoma (VS). METHODS:Records of 128 treatment-naive patients diagnosed with unilateral VS between 2012 and 2018 with serial audiometric assessment and MRI were reviewed. Tumor growth rates were determined from initial and final tumor volumes, with a median follow-up of 24.3 months (IQR 8.5-48.8 months). Hearing changes were based on pure tone averages, speech discrimination scores, and American Academy of Otolaryngology-Head and Neck Surgery hearing class. Primary outcomes were the loss of class A hearing and loss of serviceable hearing, estimated using the Kaplan-Meier method and with associations estimated from Cox proportional hazards models and reported as hazard ratios. RESULTS:Larger initial tumor size was associated with an increased risk of losing class A (HR 1.5 for a 1-cm3 increase; p = 0.047) and serviceable (HR 1.3; p < 0.001) hearing. Additionally, increasing volumetric tumor growth rate was associated with elevated risk of loss of class A hearing (HR 1.2 for increase of 100% per year; p = 0.031) and serviceable hearing (HR 1.2; p = 0.014). Hazard ratios increased linearly with increasing growth rates, without any evident threshold growth rate that resulted in a large, sudden increased risk of hearing loss. CONCLUSIONS:Larger initial tumor size and faster tumor growth rates were associated with an elevated risk of loss of class A and serviceable hearing.

OBJECTIVE:Meningiomas that arise primarily within the cavernous sinus are often believed to be more indolent in their growth pattern. Despite this perceived growth pattern, disabling symptoms can arise even with small tumors. While research has been done on cavernous sinus meningiomas (CSMs) and their treatment, very little is known about their natural growth rates. With a better understanding of the growth rate of CSM, patient treatment and guidance can be can optimized and individualized. The goal of this study was to determine volumetric growth rates of untreated CSMs. METHODS:Thirty-seven patients with 166 MR images obtained between May 2004 and September 2019 were reviewed, with a range of 2-13 MR images per patient (average of 4.5 MR images per patient). These scans were obtained over an average follow-up period of 45.9 months (median 33.8, range 2.8-136.9 months). All imaging prior to any intervention was included in this analysis. Volumetric measurements were performed and assessed over time. RESULTS:The estimated volumetric growth rate was 23.3% per year (95% CI 10.2%-38.0%, p < 0.001), which is equivalent to an estimated volume doubling time (VDT) of 3.3 years (95% CI 2.1-7.1 years). There was no significant relationship between growth rate and patient age (p = 0.09) or between growth rate and patient sex (p = 0.78). The median absolute growth rate was 41% with a range of -1% to 1793%. With a definition of "growth" as an increase of greater than 20% during the observed period, 65% of tumors demonstrated growth within their observation interval. Growth rates for each tumor were calculated and tumors were segmented based on growth rate. Of 37 patients, 22% (8) demonstrated no growth (< 5% annual growth, equivalent to a VDT > 13.9 years), 32% (12) were designated as slow growth (annual growth rate 5%-20%, VDT 3.5-13.9 years), 38% (14) were found to have medium growth (annual growth rate 20%-100%, VDT 0.7-3.5 years), and 8% were considered fast growing (annual growth rate > 100%, VDT < 0.7 years). CONCLUSIONS:This study evaluated CSM volumetric growth rates. A deeper understanding of the natural history of untreated CSMs allows for better counseling and management of patients.

INTRODUCTION:Automated text messaging programs have been studied as a treatment tool, but have not been studied as an outreach tool to increase the reach of smoking cessation treatment. AIMS AND METHODS:Two distinct text messaging programs were developed. One was aimed at connecting smokers to quitline phone counseling via text message (Text4Coach [T4C]) and the other was aimed at connecting smokers to a smoking cessation text messaging program (Text&Quit [T&Q]). Adult daily smokers with Medicaid insurance (N = 80) were recruited from the Emergency Department at an urban hospital and randomized to T4C or T&Q. The primary outcome was program reach. RESULTS:Outreach text messages were found to have moderately high uptake, with the majority of participants (63.8%) opting into their assigned tobacco treatment program and younger and female participants more likely to opt in (p < .01). Receipt of the treatment portion of the program differed among the programs with 67.5% of T&Q receiving the treatment program and 27.5% of T4C receiving the program (p < .001). Most participants across both groups replied to at least one message (71.3%) and very few unsubscribed from the service over the 3-week trial. The majority of participants reported overall satisfaction with their program (63.8%), found it helpful for quitting smoking (60.0%) and would recommend the program to a friend (62.5%). Overall, 11 (13.8%) participants reported being abstinent from smoking for the past 7 days at follow-up, with no differences between groups. CONCLUSIONS:Outreach text messages were found to have moderately high reach among Medicaid smokers. Larger trials are needed to evaluate the impact of such programs on helping low-income smokers quit. IMPLICATIONS:Automated text messaging programs have been tested as a treatment tool, but have not been tested as an outreach tool to increase the reach of smoking cessation treatment. This study tests a new way of conducting outreach to smokers in a health system through text messages. It tests the effect of outreach on (1) rates of opting in and (2) successful treatment delivery. Results may inform new models of providing outreach for tobacco treatment in health systems.

Establishing a causal link between neural function and behavioral output has remained a challenging problem. Commonly used perturbation techniques enable unprecedented control over intrinsic activity patterns and can effectively identify crucial circuit elements important for specific behaviors. However, these approaches may severely disrupt activity, precluding an investigation into the behavioral relevance of moment-to-moment neural dynamics within a specified brain region. Here we discuss the application of mild focal cooling to slow down intrinsic neural circuit activity while preserving its overall structure. Using network modeling and examples from multiple species, we highlight the power and versatility of focal cooling for understanding how neural dynamics control behavior and argue for its wider adoption within the systems neuroscience community.

OBJECTIVES/OBJECTIVE:A software tool (EasyMDT) that measures temporal modulation detection thresholds of a broadband noise carrier is presented. EasyMDT is designed to be both easy and quick to promote the use in environments where testing time is limited, and testers may not have extensive technical expertise to use typical research software. In addition, by providing a standardized stimulus and protocol, data collected by all groups using the software can be compared directly. Details of EasyMDT, including a description of the protocol, stimuli, interface and how to obtain the software, are provided along with representative sample data from both normal-hearing listeners and cochlear implant (CI) users. Performance with the EasyMDT is compared with speech understanding metrics as well as a metric of spectral-temporal resolution. DESIGN/METHODS:A "Full Curve" of modulation detection thresholds is measured using a three-interval forced-choice adaptive task in a single block for 7 modulation frequencies (10, 50, 75, 100, 150, 200, and 300 Hz). Similarly, the modulation detection thresholds were measured for only one modulation frequency in a block (either 100 Hz or 150 Hz). Modulation detection thresholds and block duration were recorded. In addition, performance on speech recognition tasks (CNC words, consonant identification, vowel identification, and AzBio sentences in noise) and a spectral-temporal resolution task (SMRT; Aronoff and Landsberger) were measured. Modulation detection thresholds were measured for both normal-hearing listeners and CI users. Only CI users participated in the speech and spectral-temporal tests. RESULTS:Modulation detection thresholds measured with EasyMDT were consistent with those previously reported from other laboratories. Modulation detection thresholds at a single modulation frequency (100 Hz or 150 Hz) were predictive of modulation detection thresholds measured as part of the Full Curve consisting of all 7 modulation frequencies. Testing durations for CI users dropped from an average of over 18 minutes for the Full Curve to under 3 minutes for either of the single modulation frequency measures. Modulation detection thresholds at 100 Hz correlated with CNC words, consonant identification, and AzBio sentences in noise, but not vowel identification. No correlations were found between modulation detection and spectral-temporal resolution. CONCLUSIONS:The EasyMDT is designed to be an easy-to-use tool that provides a nonlinguistic measure that can predict speech understanding. The test duration is short enough that it can be incorporated into clinical practice or as part of an experimental battery. The software is available for free download at https://www.ear-lab.org/software-downloads.html. The software is designed to have a minimum barrier of entry as well as provide a standardized protocol allowing direct comparison of modulation detection thresholds across studies and groups.

Most head and neck paragangliomas (PGLs) are biochemically silent and often present with recurrence and metastases in association with hereditary syndromes. Whole-body functional imaging is increasingly used to detect tumor extent and guide treatment planning of PGLs. [68Ga]-DOTATATE, which targets somatostatin receptor 2 (SSTR2) overexpression, has emerged as a sensitive functional imaging modality in PGLs. We present a patient with metastatic glomus caroticum PGL in whom [68Ga]-DOTATATE PET/MRI provided a more accurate characterization of metastatic extent, as compared to gadolinium-enhanced MRI of the neck and whole body [18F]-FDG PET/CT. We then review the current literature and discuss the imaging implications of [68Ga]-DOTATATE PET/MRI in PGLs.

ABSTRACT/UNASSIGNED:Migraine affects ∼15% of the world's population greatly diminishing their quality of life. Current preventative treatments are effective in only a subset of migraine patients, and while cannabinoids appear beneficial in alleviating migraine symptoms, central nervous system (CNS) side effects limit their widespread use. We developed peripherally-restricted cannabinoids (PRCBs) that relieve chronic pain symptoms of cancer and neuropathies, without appreciable CNS side effects or tolerance development. Here we determined PRCB effectiveness in alleviating hypersensitivity symptoms in mouse models of migraine and medication overuse headache (MOH). Chronic glyceryl trinitrate (GTN, 10 mg/kg) administration led to increased sensitivity to mechanical stimuli, and increased expression of phosphorylated protein kinase A (p-PKA), neuronal nitric oxide synthase (nNOS), and transient receptor potential ankyrin 1 (TRPA1) proteins in trigeminal ganglia. PRCB pretreatment, but not posttreatment, prevented behavioral and biochemical correlates of GTN-induced sensitization. Low pH- and allyl isothiocyanate-activated currents in acutely isolated trigeminal neurons were reversibly attenuated by PRCB application. Chronic GTN treatment significantly enhanced these currents. Chronic sumatriptan treatment also led to development of allodynia to mechanical and cold stimuli which was slowly reversible after sumatriptan discontinuation. Subsequent challenge with a previously ineffective low-dose GTN (0.1-0.3 mg/kg) revealed latent behavioral sensitization and increased expression of p-PKA, nNOS, and TRPA1 proteins in trigeminal ganglia. PRCB pretreatment prevented all behavioral and biochemical correlates of allodynia and latent sensitization. Importantly, chronic PRCB treatment alone did not produce any behavioral or biochemical signs of sensitization. These data validate peripheral cannabinoid receptors as potential therapeutic targets in migraine and MOH.

Maternal care, including by non-biological parents, is important for offspring survival^1-8. Oxytocin^1,2,9-15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress¹⁵. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Meniere's disease (MD) is a debilitating condition characterized by hearing loss, vertigo, and tinnitus. The objective of this study was to systematically investigate outcomes in MD after cochlear implantation (CoI), with and without labyrinthectomy. STUDY DESIGN/METHODS:Systematic review and meta-analysis. METHODS:A systematic review of articles in Medline and Embase was performed to identify all studies of patients with MD who underwent CoI. This analysis evaluates outcomes of speech recognition, pure tone audiometry, vertigo, tinnitus, and quality of life. RESULTS:Of 321 studies identified, 37 were included, involving 216 patients. Mean age at implantation was 61.4 years (range 27-85 years) with average length of follow-up at 1.7 years (range 0-9 years). Forty-four (20.4%) patients underwent labyrinthectomy. Meta-analysis demonstrated significant improvements in audiometric outcomes following CoI. There was a statistically significant improvement in Hearing in Noise Test performance, with a mean difference improvement of 44.7 (95% confidence interval [CI] [8.8, 80.6]) at 6 months and 60.1 (95% CI [35.3, 85.0]) at 12 months. The Freiburger Monosyllabic Test (FMT) and Consonant-Nucleus-Consonant (CNC) also improved significantly, with mean difference improvements of 46.2 (95% CI [30.0, 62.4]) for FMT and 19.3 (95% CI [8.1, 30.4]) for CNC. There was a statistically significant decrease in tinnitus, as measured by a mean difference reduction of 48.1 (95% CI [1.0, 95.2]) in the Tinnitus Handicap Index. CONCLUSIONS:CoI with and without simultaneous labyrinthectomy is a viable treatment option for patients with MD, yielding high rates of tinnitus suppression and vertigo control. Post-CoI MD patients demonstrate similar postoperative speech perception outcomes to non-MD implant recipients. Laryngoscope, 2021.