Faculty Bibliography

Purpose/UNASSIGNED:The aim of this study was to investigate improvements in swallowing function and physiology in a series of healthy older adults with radiographically confirmed dysphagia, following completion of an exercise-based swallowing intervention. Patients and methods/UNASSIGNED:Nine otherwise healthy older adults (six females, mean age =75.3, SD =5.3) had confirmed impairments in swallowing safety and/or efficiency on a modified barium swallow study. Each participant completed an 8-week swallowing treatment protocol including effortful swallows, Mendelsohn maneuvers, tongue-hold swallows, supraglottic swallows, Shaker exercises and effortful pitch glides. Treatment sessions were conducted once per week with additional daily home practice. Penetration-Aspiration Scale and the Modified Barium Swallowing Impairment Profile (MBSImP) were scored in a blind and randomized fashion to examine changes to swallowing function and physiology from baseline to post-treatment. Results/UNASSIGNED:There were significant improvements in swallowing physiology as represented by improved oral and pharyngeal composite scores of the MBSImP. Specific components to demonstrate statistical improvement included initiation of the pharyngeal swallow, laryngeal elevation and pharyngeal residue. There was a nonsignificant reduction in median PAS scores. Conclusion/UNASSIGNED:Swallowing physiology can be improved using this standardized high-intensity exercise protocol in healthy adults with evidence of dysphagia. Future research is needed to examine the individual potential of each exercise in isolation and to determine ideal dose and frequency. Studies on various etiological groups are warranted.

Introduction: Edema is a frequent clinical observation after chemoradiation treatment (CRT) for oral/oropharyngeal cancer (O/OP Ca). Our aims were to reliably quantify edema from video fluoroscopy (VF) at 3 time points (baseline 1-month (mo) and 4-mo post CRT) and to explore the relationship between edema and (a) patient-reported outcomes (EAT-10) and (b) functional impairment on VF (Dynamic Imaging Grade of Swallowing Toxicity DIGEST).
Material(s) and Method(s): 15 patients (7 M; age 38-76) with O/OP Ca received radiotherapy (70 Gy 7 weeks) and 3 weekly doses of cisplatin. VF was completed pre-CRT 1-mo and 4-mo post-CRT. Edema was captured by measuring posterior pharyngeal wall (PPW) thickness and pharyngeal area (PA) at rest. EAT-10 surveys were completed on the day of VF. DIGEST scores were rated according to published protocols. Mixed model repeated measures ANOVAs were run for each edema measure (PPW PA) to test for the effect of TIME EAT-10 and DIGEST while controlling for age and sex.
Result(s): For PPW we found a main effect of TIME but not EAT-10 or DIGEST (Table 1). Post-hoc comparisons revealed a significant worsening from mean at baseline (4.1 mm) to 4-mo post CRT (6.0 mm) but not at 1-mo post CRT (5.4 mm). For PA we found a main effect of TIME and of DIGEST grade (Table 2). Mean PA was significantly smaller at 1-mo post CRT (527 mm2) compared with baseline (716 mm2) but not different from 4-mo post CRT (652 mm2). Mean PA was significantly greater for grade 2 (751 mm2) compared with grade 0 (442 mm2) contrary to the hypothesized direction.
Conclusion(s): The data confirm that post-CRT edema can be quantified on 2D lateral VF. Patient reported outcomes (EAT-10) were not independently predictive of edema. Surprisingly worse DIGEST grades were associated with increased pharyngeal area at rest perhaps reflecting impairment associated with pharyngeal atrophy not edema. Future work should monitor patients' edema and swallow function over a longer time period and at a greater frequency

Iatrogenic facial nerve (FN) injury is one of the most feared complications of otologic surgery. Dehiscence of the bony covering of the FN within the temporal bone increases FN vulnerability to accidental injury. High-resolution computed tomography (HRCT) of the temporal bone is used preoperatively to assess middle ear and mastoid anatomy; however, it is unreliable for detecting facial canal dehiscence. In this study, our aim was to determine if preoperative percutaneous FN stimulation could predict middle ear facial canal dehiscence. Between January 2015 and February 2017, we performed preoperative HRCT and percutaneous FN stimulation on adult patients who underwent otologic surgery at our institution. Stimulation was performed with a monopolar probe placed on the skin over the stylomastoid foramen. Electrical stimuli ranged from 0 to 40 milliamperes (mA). Recordings were made from ipsilateral facial muscles. Dependent variables included threshold to compound muscle action potential (CMAP), threshold to maximum amplitude of CMAP, and maximum amplitude of CMAP for each muscle. A retrospective chart review was performed. Seventy patients met inclusion criteria. Of the 24 with an intraoperatively confirmed dehiscence, 10 were identified preoperatively by the attending surgeon on HRCT. Averages of the lowest recorded threshold to CMAP (5.1mA v. 9.1mA), and an average of the threshold to CMAP (8.9 mA. 11.8 mA) of dehiscent versus non-dehiscent nerves were significantly different (p < .05). In conclusion, percutaneous FN stimulation is a simple and cost-effective tool that can give the surgeon important preoperative information about FN anatomy.

Pain is a complex multidimensional experience encompassing sensory-discriminative, affective-motivational and cognitive-emotional components mediated by different neural mechanisms. Investigations of neurophysiological signals from simultaneous recordings of two or more cortical circuits may reveal important circuit mechanisms on cortical pain processing. The anterior cingulate cortex (ACC) and primary somatosensory cortex (S1) represent two most important cortical circuits related to sensory and affective processing of pain. Here, we recorded in vivo extracellular activity of the ACC and S1 simultaneously from male adult Sprague-Dale rats (n = 5), while repetitive noxious laser stimulations were delivered to animalÕs hindpaw during pain experiments. We identified spontaneous pain-like events based on stereotyped pain behaviors in rats. We further conducted systematic analyses of spike and local field potential (LFP) recordings from both ACC and S1 during evoked and spontaneous pain episodes. From LFP recordings, we found stronger phase-amplitude coupling (theta phase vs. gamma amplitude) in the S1 than the ACC (n = 10 sessions), in both evoked (p = 0.058) and spontaneous pain-like behaviors (p = 0.017, paired signed rank test). In addition, pain-modulated ACC and S1 neuronal firing correlated with the amplitude of stimulus-induced event-related potentials (ERPs) during evoked pain episodes. We further designed statistical and machine learning methods to detect pain signals by integrating ACC and S1 ensemble spikes and LFPs. Together, these results reveal differential coding roles between the ACC and S1 in cortical pain processing, as well as point to distinct neural mechanisms between evoked and putative spontaneous pain at both LFP and cellular levels.

With an increasing awareness of mental health issues and neurological disorders, "understanding the brain" is one of the biggest current challenges in biological research. This has been recognised by both governments and funding agencies, and it includes the need to understand connectivity of brain regions and coordinated network activity, as well as cellular and molecular mechanisms at play. In this chapter, we will describe how we have taken advantage of different proteomic techniques to unravel molecular mechanisms underlying two modulators of neuronal function: Neurotrophins and antipsychotics.

Oral cancer patients report severe function-induced pain; severity is greater in females. We hypothesize that a neutrophil-mediated endogenous analgesic mechanism is responsible for sex differences in nociception secondary to oral squamous cell carcinoma (SCC). Neutrophils isolated from the cancer-induced inflammatory microenvironment contain β-endorphin protein and are identified by the Ly6G⁺ immune marker. We previously demonstrated that male mice with carcinogen-induced oral SCC exhibit less nociceptive behavior and a higher concentration of neutrophils in the cancer microenvironment compared to female mice with oral SCC. Oral cancer cells secrete granulocyte colony stimulating factor (G-CSF), a growth factor that recruits neutrophils from bone marrow to the cancer microenvironment. We found that recombinant G-CSF (rG-CSF, 5 μg/mouse, intraperitoneal) significantly increased circulating Ly6G⁺ neutrophils in the blood of male and female mice within 24 h of administration. In an oral cancer supernatant mouse model, rG-CSF treatment increased cancer-recruited Ly6G⁺ neutrophil infiltration and abolished orofacial nociceptive behavior evoked in response to oral cancer supernatant in both male and female mice. Local naloxone treatment restored the cancer mediator-induced nociceptive behavior. We infer that rG-CSF-induced Ly6G⁺ neutrophils drive an endogenous analgesic mechanism. We then evaluated the efficacy of chronic rG-CSF administration to attenuate oral cancer-induced nociception using a tongue xenograft cancer model with the HSC-3 human oral cancer cell line. Saline-treated male mice with HSC-3 tumors exhibited less oral cancer-induced nociceptive behavior and had more β-endorphin protein in the cancer microenvironment than saline-treated female mice with HSC-3 tumors. Chronic rG-CSF treatment (2.5 μg/mouse, every 72 h) increased the HSC-3 recruited Ly6G⁺ neutrophils, increased β-endorphin protein content in the tongue and attenuated nociceptive behavior in female mice with HSC-3 tumors. From these data, we conclude that neutrophil-mediated endogenous opioids warrant further investigation as a potential strategy for oral cancer pain treatment.