Ambulatory Voice Biofeedback: Acquisition and Retention of Modified Daily Voice Use in Patients With Phonotraumatic Vocal Hyperfunction.

PURPOSE: Voice ambulatory biofeedback (VAB) has potential to improve carryover of therapeutic voice use into daily life. Previous work in vocally healthy participants demonstrated that motor learning inspired variations to VAB produced expected differences in acquisition and retention of modified daily voice use. This proof-of-concept study was designed to evaluate whether these VAB variations have the same desired effects on acquisition and retention in patients with phonotraumatic vocal hyperfunction (PVH). METHOD: Seventeen female patients with PVH wore an ambulatory voice monitor for 6 days: three baseline days, one biofeedback day, one short-term retention day, and one long-term retention day. Short- and long-term retention were 1- and 7-days postbiofeedback, respectively. Patients were block-randomized to receive one of three types of VAB: 100%, 25%, and Summary. Performance was measured in terms of adherence time below a subject-specific vocal intensity threshold. RESULTS: All three types of VAB produced a biofeedback effect with 13 out of 17 patients displaying an increase in adherence time compared to baseline days. Additionally, multiple patients from each VAB group increased their adherence time during short- and/or long-term retention monitoring compared to baseline. CONCLUSIONS: These findings show that VAB can be associated with acquisition and retention of desired voice use in patients with PVH. Specifically, all three feedback types improved multiple patients' performance and retention for up to 1 week after biofeedback removal. Future work can investigate the impact of incorporating VAB into voice therapy.

Subcutaneous Ports for Chronic Nerve Cuff and Intramuscular Electrode Stimulation in Animal Models.

OBJECTIVE: Tracking recovery after nerve injury may require many intermittent assessments over long periods, preferably with non- or minimally invasive methods. We developed subcutaneous electrical connection ports (ECPs) for repeated connection to nerve cuff or intramuscular electrodes via transdermal needles and evaluated them during studies of laryngeal reinnervation. STUDY DESIGN: Animal experiment. SETTING: Laboratory. METHODS: ECPs were designed and 3-dimensionally printed for connection to bipolar electrodes with biocompatible polymers. Dual compartments filled with conductive silicone capped with nonconductive silicone were used to make the connections between electrode leads and transdermally inserted needles. Ten dogs (19-29 kg) were implanted with 22 ECPs. In 7 dogs, 11 electrodes were placed on recurrent laryngeal nerves proximal to transection and suture repair to track laryngeal reinnervation. In 6 dogs, 8 spinal accessory nerve cuff electrodes were used to stimulate neck muscle contraction. In 2 dogs, 3 electrodes were implanted in the thyroarytenoid muscle. Stimulation thresholds, electromyography, and videolaryngoscopic imaging were obtained in 156 tests over survival periods up to 32 months. Stimulation data provided information about ECP performance. RESULTS: ECPs added negligible resistance to electrodes (mean ± SD, 2.14 ± 0.9 Ω). Despite some electrode leads breaking distally, ECPs were reliable and well tolerated at implant sites and enabled periodic assessment of nerve and muscle function over the time course of laryngeal reinnervation. Histology showed ECP encapsulation as thin layers of connective tissue and minimal acute inflammation. CONCLUSION: Custom ECPs are easily fabricated and cause little tissue reaction over months to years of subcutaneous implantation, facilitating long-term physiologic studies.

Development of a Closed-Loop Stimulator for Laryngeal Reanimation: Part 2. Device Testing in the Canine Model of Laryngeal Paralysis.

OBJECTIVE:: Laryngeal paralysis of central or peripheral origin can potentially be treated using functional electrical stimulation (FES) of laryngeal muscles. Experiments in canines (dogs) were performed using implant prototypes capable of closed-loop FES to refine engineering designs and specifications, test surgical approaches for implantation, and better understand the in vivo effects of laryngeal muscle stimulation on short- and long-term glottic function. STUDY DESIGN:: Prospective, laboratory. METHODS:: We designed and tested a series of microprocessor-based implantable devices that can stimulate glottic opening or closing based on input from physiological control signals (real-time processing of electromyographic [EMG] signals). After acute device testing experiments, 2 dogs were implanted for 8 and 24 months, with periodic testing of closed-loop laryngeal muscle stimulation triggered from EMG signals. In total, 5 dogs were tested for the effects of laryngeal muscle stimulation on vocal fold (VF) posturing in larynges with nerve supplies that were intact (7 VFs), synkinetically reinnervated (2 VFs), or chronically denervated (1 VF). In 3 cases, the stimulation was combined with airflow-driven phonation to study the consequent modulation of phonatory parameters. RESULTS:: Initial device prototypes used inductive coupling for power and communication, while later iterations used battery power and infrared light communication (detailed descriptions are provided in the Part 1 companion paper). Two animals were successfully implanted with the inductively powered units, which operated until removed at 8 months in 1 animal or for more than 16 months in the second animal. Surgically, the encapsulated implants were well tolerated, and procedures for placing, attaching, and connecting the devices were developed. To simulate EMG control signals in anesthetized animals, we created 2 types of nerve/muscle signal sources. In one approach, a neck muscle had a cuff electrode placed on its motor nerve that was connected to transdermal electrical connection ports for periodic testing. In the second approach, the recurrent laryngeal nerve on one side of the larynx was stimulated to generate a VF EMG signal, which was then used to trigger FES of the paralyzed contralateral side (eg, restoring VF movement symmetry). Implant testing identified effective stimulation parameters and closed-loop stimulation artifact rejection techniques for FES of both healthy and paralyzed VFs. Stimulation levels effective for VF adduction did not cause signs of discomfort during awake testing. CONCLUSION:: Our inductive and battery-powered prototypes performed effectively during in vivo testing, and the 2 units that were implanted for long-term evaluation held up well. As a proof of concept, we demonstrated that elicited neck strap muscle or laryngeal EMG potentials could be used as a control signal for closed-loop stimulation of laryngeal adduction and vocal pitch modulation, depending on electrode positioning, and that VFs were stimulable in the presence of synkinetic reinnervation or chronic denervation.

Ambulatory Voice Biofeedback: Relative Frequency and Summary Feedback Effects on Performance and Retention of Reduced Vocal Intensity in the Daily Lives of Participants With Normal Voices.

Purpose: Ambulatory voice biofeedback has the potential to significantly improve voice therapy effectiveness by targeting carryover of desired behaviors outside the therapy session (i.e., retention). This study applies motor learning concepts (reduced frequency and delayed, summary feedback) that demonstrate increased retention to ambulatory voice monitoring for training nurses to talk softer during work hours. Method: Forty-eight nurses with normal voices wore the Voice Health Monitor (Mehta, Zañartu, Feng, Cheyne, & Hillman, 2012) for 6 days: 3 baseline days, 1 biofeedback day, 1 short-term retention day, and 1 long-term retention day. Participants were block-randomized into 3 different biofeedback groups: 100%, 25%, and Summary. Performance was measured in terms of compliance time below a participant-specific vocal intensity threshold. Results: All participants exhibited a significant increase in compliance time (Cohen's d = 4.5) during biofeedback days compared with baseline days. The Summary feedback group exhibited statistically smaller performance reduction during both short-term (d = 1.14) and long-term (d = 1.04) retention days compared with the 100% feedback group. Conclusions: These findings suggest that modifications in feedback frequency and timing affect retention of a modified vocal behavior in daily life. Future work calls for studying the potential beneficial impact of ambulatory voice biofeedback in participants with behaviorally based voice disorders.

Integration of Motor Learning Principles Into Real-Time Ambulatory Voice Biofeedback and Example Implementation Via a Clinical Case Study With Vocal Fold Nodules.

PURPOSE: Ambulatory voice biofeedback (AVB) has the potential to significantly improve voice therapy effectiveness by targeting one of the most challenging aspects of rehabilitation: carryover of desired behaviors outside of the therapy session. Although initial evidence indicates that AVB can alter vocal behavior in daily life, retention of the new behavior after biofeedback has not been demonstrated. Motor learning studies repeatedly have shown retention-related benefits when reducing feedback frequency or providing summary statistics. Therefore, novel AVB settings that are based on these concepts are developed and implemented. METHOD: The underlying theoretical framework and resultant implementation of innovative AVB settings on a smartphone-based voice monitor are described. A clinical case study demonstrates the functionality of the new relative frequency feedback capabilities. RESULTS: With new technical capabilities, 2 aspects of feedback are directly modifiable for AVB: relative frequency and summary feedback. Although reduced-frequency AVB was associated with improved carryover of a therapeutic vocal behavior (i.e., reduced vocal intensity) in a patient post-excision of vocal fold nodules, causation cannot be assumed. CONCLUSIONS: Timing and frequency of AVB schedules can be manipulated to empirically assess generalization of motor learning principles to vocal behavior modification and test the clinical effectiveness of AVB with various feedback schedules.

Real-time estimation of aerodynamic features for ambulatory voice biofeedback.

The development of ambulatory voice monitoring devices has the potential to improve the diagnosis and treatment of voice disorders. In this proof-of-concept study, real-time biofeedback is incorporated into a smartphone-based platform that records and processes neck surface acceleration. The focus is on utilizing aerodynamic measures of vocal function as a basis for biofeedback. This is done using regressed Z-scores to compare recorded values to normative estimates based on sound pressure level and fundamental frequency. Initial results from the analysis of different voice qualities suggest that accelerometer-based estimates of aerodynamic parameters can be used for real-time ambulatory biofeedback.

The Effect of Voice Ambulatory Biofeedback on the Daily Performance and Retention of a Modified Vocal Motor Behavior in Participants With Normal Voices.

PURPOSE: Ambulatory biofeedback has potential to improve carryover of newly established vocal motor behaviors into daily life outside of the clinic and warrants systematic research that is lacking in the literature. This proof-of-concept study was designed to establish an empirical basis for future work in this area by formally assessing whether ambulatory biofeedback reduces daily vocal intensity (performance) and the extent to which this change remains after biofeedback removal (retention). METHOD: Six participants with normal voices wore the KayPENTAX Ambulatory Phonation Monitor for 3 baseline days followed by 4 days with biofeedback provided on odd days. RESULTS: Compared to baseline days, participants exhibited a statistically significant decrease in mean vocal intensity (4.4 dB) and an increase in compliance (16.8 percentage points) when biofeedback was provided above a participant-specific intensity threshold. After biofeedback removal, mean vocal intensity and compliance reverted back to baseline levels. CONCLUSIONS: These findings suggest that although current ambulatory biofeedback approaches have potential to modify a vocal motor behavior, the modified behavior may not be retained after biofeedback removal. Future work calls for the testing of more innovative ambulatory biofeedback approaches on the basis of motor control and learning theories to improve retention of a desired vocal motor behavior.

Talker identification across source mechanisms: experiments with laryngeal and electrolarynx speech.

PURPOSE: The purpose of this study was to determine listeners' ability to learn talker identity from speech produced with an electrolarynx, explore source and filter differentiation in talker identification, and describe acoustic-phonetic changes associated with electrolarynx use. METHOD: Healthy adult control listeners learned to identify talkers from speech recordings produced using talkers' normal laryngeal vocal source or an electrolarynx. Listeners' abilities to identify talkers from the trained vocal source (Experiment 1) and generalize this knowledge to the untrained source (Experiment 2) were assessed. Acoustic-phonetic measurements of spectral differences between source mechanisms were performed. Additional listeners attempted to match recordings from different source mechanisms to a single talker (Experiment 3). RESULTS: Listeners successfully learned talker identity from electrolarynx speech but less accurately than from laryngeal speech. Listeners were unable to generalize talker identity to the untrained source mechanism. Electrolarynx use resulted in vowels with higher F1 frequencies compared with laryngeal speech. Listeners matched recordings from different sources to a single talker better than chance. CONCLUSIONS: Electrolarynx speech, although lacking individual differences in voice quality, nevertheless conveys sufficient indexical information related to the vocal filter and articulation for listeners to identify individual talkers. Psychologically, perception of talker identity arises from a "gestalt" of the vocal source and filter.

Safety and dosing of bevacizumab (avastin) for the treatment of recurrent respiratory papillomatosis.

OBJECTIVES: Increasing evidence supports the use of laryngeal injections of the antiangiogenic agent bevacizumab (Avastin) for the adjuvant treatment of recurrent respiratory papillomatosis (RRP). A recent prospective open-label investigation, approved by the US Food and Drug Administration, employing 12.5 mg of sublesional bevacizumab demonstrated single-site efficacy without complications; however, the safety of multiple-site injections and higher dosing has not yet been reported. The primary objective of this study was to report on the safety of increased doses of bevacizumab for the treatment of RRP. METHODS: Two cohorts of adult patients were evaluated. In the first group, a prospective analysis was performed on patients with a diagnosis of laryngeal RRP after t heir participation in th e initial clinical trial with a single-site lowerdose (7.5 to 12.5 mg). They received higher doses of sublesional laryngeal bevacizumab (15 to 50 mg total) with detailed physiologic, hematologic, and serum chemistry measurements performed before and after each bevacizumab injection. A second cohort of patients received sublesional laryngeal injections of bevacizumab (15 to 88 mg total) without physiologic measurements and underwent a retrospective analysis of reported complications. RESULTS: One hundred consecutive laryngeal injection sessions (office, 87; operating room, 13) with bevacizumab were performed in 43 patients, with a mean dose of 30 mg total per treatment (range, 15 to 88 mg). Sixty-three of the 100 sessions were accompanied by KTP laser photoangiolysis of the papilloma prior to bevacizumab injections. Eighteen patients (cohort 1) underwent detailed physiologic assessment, and no dysfunction was observed. There were no local or systemic complications of bevacizumab administration. The second group of 25 patients (cohort 2) also reported no significant local or systemic complications. Neither patient group was observed to have a local wound problem in the larynx. CONCLUSIONS: This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements in pharmacologic concentration and drug delivery will determine the optimal treatment regimens in the future.

Local injection of bevacizumab (Avastin) and angiolytic KTP laser treatment of recurrent respiratory papillomatosis of the vocal folds: a prospective study.

OBJECTIVES: Photoangiolytic laser treatment of recurrent respiratory papillomatosis (RRP) is effective, but does not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the adjunctive effect on disease recurrence. Since bevacizumab is a new therapeutic modality for RRP, there were also primary safety objectives to determine whether there was a pegative impact on the voice and whether there were local or systemic complications. METHODS: A prospective open-label investigation was conducted in 20 adult patients with bilateral vocal fold RRP. The patients underwent planned 532-nm pulsed KTP laser photoangiolysis of bilateral glottal disease 4 times with an approximately 6-week interval between procedures. At each planned laser procedure, the vocal fold that on initial presentation had a greater volume of disease also underwent 4 serial sublesional bevacizumab injections (7.5 to 12.5 mg in 0.3 to 0.5 mL). A sham injection with saline solution was administered to the other vocal fold as a control. Disease resolution was compared between subjects' vocal folds, and objective measures of vocal function (acoustic, aerodynamic), as well as patients' self-assessments of vocal function (Voice-Related Quality of Life survey), were obtained. RESULTS: All 20 patients completed the study, and there were no local or systemic complications. After 4 injections, 3 of the 20 patients had no discernible disease in either vocal fold. Of the remaining 17 subjects, 16 had less disease in the bevacizumab-treated vocal fold despite starting with more disease. Only 1 of the 17 had more disease in the bevacizumab-treated vocal fold after 4 injections. Moreover, 7 of the 20 patients (35%) did not require a laser procedure in the vocal fold that had received 4 bevacizumab injections, as compared with 3 of the 20 vocal folds (15%) that were treated with laser alone. All of the vocal function measures displayed statistically significant posttreatment improvements, except for average fundamental frequency in the 3 female patients, in whom it fell below the normal range. CONCLUSIONS: This prospective investigation provided evidence that bevacizumab injections enhanced KTP laser treatment of glottal papillomatosis without systemic or local complications. Coupling the antiangiogenesis agent bevacizumab with KTP laser photoangiolysis is conceptually synergistic and scientifically promising since the mechanisms of action are complementary.

Microlaryngoscopic and office-based injection of bevacizumab (Avastin) to enhance 532-nm pulsed KTP laser treatment of glottal papillomatosis.

OBJECTIVES: Photoangiolytic lasers effectively treat glottal papillomatosis, but do not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the effect on disease recurrence and phonatory function. METHODS: A retrospective investigation was done in a pilot group of 10 adult patients with bilateral glottal papillomatosis who had prior angiolytic laser treatment with established patterns of recurrence. The patients underwent 5 bevacizumab injections (5 to 10 mg) into the diseased vocal folds along with 532-nm pulsed KTP laser photoangiolysis treatments 4 to 6 weeks apart. Their disease resolution was compared to findings from prior laser treatment alone, and objective measures of vocal function (acoustic, aerodynamic, Voice-Related Quality of Life survey) were obtained. RESULTS: All 10 patients had a greater than 90% reduction in recurrence. Four of the 10 had resolution. Four of the 10 have limited recurrent or persistent disease, receive injections of bevacizumab at 8- to 12-week intervals, and have not required laser treatment. Two of the 10 have ongoing periodic office-based KTP laser treatment along with bevacizumab injections. No patient has required microlaryngeal surgery with general anesthesia, and all 10 have had substantial improvement in vocal function. CONCLUSIONS: This pilot investigation provides preliminary evidence that bevacizumab injections enhance photoangiolytic laser treatment of glottal papillomatosis while enhancing phonatory function. Coupling an antiangiogenesis agent with pulsed KTP laser photoangiolysis is conceptually promising, since the mechanisms of action are complementary.

Electromyographic control of a hands-free electrolarynx using neck strap muscles.

UNLABELLED: Three individuals with total laryngectomy were studied for their ability to control a hands-free electrolarynx (EL) using neck surface electromyography (EMG) for on/off and pitch modulation. The laryngectomy surgery of participants was modified to preserve neck strap musculature for EMG-based EL control (EMG-EL), with muscles on one side maintaining natural innervation and those on the other side receiving a transferred recurrent laryngeal nerve (RLN). EMG from each side of the neck controlled the EMG-EL across a day of unstructured practice followed by a day of formal training, including EMG biofeedback. Using either control source, participants spoke intelligibly and fluently with the EMG-EL before formal training. This good initial performance did not consistently improve across testing for either control source in terms of voice timing, speech intelligibility, fluency, and intonation of interrogative versus declarative sentences. Neck strap muscles have activation patterns capable of simple alaryngeal voice control without requiring RLN transfer. LEARNING OUTCOMES: The reader will better understand (1) functionality of the hands-free electrolarynx (2) modification of laryngectomy surgery to preserve neck strap musculature and (3) performance of hands-free electrolarynx with different control sources.

Office-based treatment of glottal dysplasia and papillomatosis with the 585-nm pulsed dye laser and local anesthesia.

Treatment of glottal papillomatosis and dysplasia was mirror-guided and performed in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. Presently, the primary treatment goals, which are disease regression and voice restoration or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. In fact, general anesthesia has been appropriately considered to be an acceptable source of morbidity for the promise of a precise procedure, which usually ensures airway safety and an optimal vocal outcome. However, patients with recurrent glottal papillomatosis and keratosis with dysplasia are typically monitored with various degrees of watchful waiting until there is a subjective judgment (on the part of the patient and surgeon) that the disease is more of a liability than is the procedure to treat it. Innovations in the 585-nm pulsed dye laser delivery system have allowed for its use in the clinic with local anesthesia through the working channel of a flexible fiberoptic laryngoscope. A prospective assessment was done on 51 patients in 82 cases of recurrent glottal papillomatosis (30) and dysplasia (52). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. Five procedures could not be completed because of impaired exposure (2) or discomfort (3). Of those patients who could be treated, there was at least a 50% disease involution in 68 of 77 cases (88%) and 25% to 50% disease regression in the remaining 9 (12%). Patient self-assessment of the voice revealed that 34 of 77 were improved, 39 were unchanged, 4 were slightly worse, and none were substantially worse. These data confirm that diseased mucosa can be normalized without resection or substantial loss of vocal function. The putative mechanisms, which vary according to the fluence (energy) delivered by the laser, are photoangiolysis of sublesional microcirculation. denaturing of epithelial basement membrane linking proteins, and cellular destruction. Furthermore, this relatively safe, effective technique allowed for treatment of many patients (in a clinic setting) in whom classic surgery-related morbidity would have often delayed intervention.