Amal Isaiah

Multisensory Training Improves Auditory Spatial Processing following Bilateral Cochlear Implantation

Cochlear implants (CIs) partially restore hearing to the deaf by directly stimulating the inner ear. In individuals fitted with CIs, lack of auditory experience due to loss of hearing before language acquisition can adversely impact outcomes. For example, adults with early-onset hearing loss generally do not integrate inputs from both ears effectively when fitted with bilateral CIs (BiCIs). Here, we used an animal model to investigate the effects of long-term deafness on auditory localization with BiCIs and approaches for promoting the use of binaural spatial cues. Ferrets were deafened either at the age of hearing onset or as adults. All animals were implanted in adulthood, either unilaterally or bilaterally, and were subsequently assessed for their ability to localize sound in the horizontal plane. The unilaterally implanted animals were unable to perform this task, regardless of the duration of deafness. Among animals with BiCIs, early-onset hearing loss was associated with poor auditory localization performance, compared with late-onset hearing loss. However, performance in the early-deafened group with BiCIs improved significantly after multisensory training with interleaved auditory and visual stimuli. We demonstrate a possible neural substrate for this by showing a training-induced improvement in the responsiveness of auditory cortical neurons and in their sensitivity to interaural level differences, the principal localization cue available to BiCI users. Importantly, our behavioral and physiological evidence demonstrates a facilitative role for vision in restoring auditory spatial processing following potential cross-modal reorganization. These findings support investigation of a similar training paradigm in human CI users.

Bilateral cochlear implantation in the ferret: A novel animal model for behavioral studies

Bilateral cochlear implantation has recently been introduced with the aim of improving both speech perception in background noise and sound localization. Although evidence suggests that binaural perception is possible with two cochlear implants, results in humans are variable. To explore potential contributing factors to these variable outcomes, we have developed a behavioral animal model of bilateral cochlear implantation in a novel species, the ferret. Although ferrets are ideally suited to psychophysical and physiological assessments of binaural hearing, cochlear implantation has not been previously described in this species. This paper describes the techniques of deafening with aminoglycoside administration, surgical implantation of an intracochlear array and chronic intracochlear electrical stimulation with monitoring for electrode integrity and efficacy of stimulation. Experiments have been presented elsewhere to show that the model can be used to study behavioral and electrophysiological measures of binaural hearing in chronically implanted animals. This paper demonstrates that cochlear implantation and chronic intracochlear electrical stimulation are both safe and effective in ferrets, opening up the possibility of using this model to study potential protective effects of bilateral cochlear implantation on the developing central auditory pathway. Since ferrets can be used to assess psychophysical and physiological aspects of hearing along with the structure of the auditory pathway in the same animals, we anticipate that this model will help develop novel neuroprosthetic therapies for use in humans.

Subplate neurons are the first cortical neurons to respond to sensory stimuli

Significance Sensory experience, even at prenatal periods, can shape brain connectivity. Thus, the emergence of sensory responses is a key step in cortical development. Sensory cortical responses are thought to emerge in cortical layer 4, which is the adult target of thalamic projections. However, in developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons in the white matter. We show that subplate neurons respond to sounds before layer 4 is activated by thalamic axons. Moreover, early local field potential (LFP) responses demonstrate nascent topographic organization. Together we find that sound-evoked cortical activity and topographic organization emerge in a different layer than thought. Since subplate circuits are disrupted in autism spectrum disorder (ASD) models, disrupted emergence of sensory activity could be utilized for diagnosis and intervention. In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to layer 4 as well as the ear and eye opening. In developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons deep in the developing white matter. We investigated if subplate neurons respond to sensory stimuli. Using electrophysiological recordings in young ferrets, we show that auditory cortex neurons respond to sound at very young ages, even before the opening of the ears. Single unit recordings showed that auditory responses emerged first in cortical subplate neurons. Subsequently, responses appeared in the future thalamocortical input layer 4, and sound-evoked spike latencies were longer in layer 4 than in subplate, consistent with the known relay of thalamic information to layer 4 by subplate neurons. Electrode array recordings show that early auditory responses demonstrate a nascent topographic organization, suggesting that topographic maps emerge before the onset of spiking responses in layer 4. Together our results show that sound-evoked activity and topographic organization of the cortex emerge earlier and in a different layer than previously thought. Thus, early sound experience can activate and potentially sculpt subplate circuits before permanent thalamocortical circuits to layer 4 are present, and disruption of this early sensory activity could be utilized for early diagnosis of developmental disorders.

Can training extend current guidelines for cochlear implant candidacy

Since their introduction in the 1960s, cochlear implants (CIs) have undergone several transformations, ultimately positioning themselves as the best-performing neural prosthesis available today. They have also been recognized as a unique tool for studying the potential protective effects of patterned electrical stimulation on the developing auditory system, with results from animal models often changing the manner in which CIs are used clinically to deliver auditory information to the brain (Moore and Shannon, 2009). From the development of the first successful commercial single-channel device, they have evolved into multi-channel devices that are part of the national health programmes of several countries. From the limited speech information provided by the early, rudimentary cochlear implants, these devices are now in a position to deliver intelligible speech information to the auditory system, largely due to advances in signal processing. Concerted efforts from several disciplines, including engineering, acoustics, neurobiology and otolaryngology have ensured that the continued development of CI technology has resulted in significant benefits to individuals with profound sensorineural hearing loss.

Outcomes after adenotonsillectomy using a fixed anesthesia protocol in children with obstructive sleep apnea.

OBJECTIVE To document the effects of a fixed anesthesia protocol on peri-operative events in children undergoing adenotonsillectomy for obstructive sleep apnea (OSA). METHODS A non-randomized prospective study was conducted during the years 2011-2013 within a setting of a tertiary-level university hospital. Sixty five children with polysomnographically proven OSA undergoing adenotonsillectomy were enrolled in the study and stratified into three groups based on severity. The relationship between severity of OSA as determined by apnea-hypopnea index (AHI) and oxygen saturation (SpO2) nadir were compared with time taken to (i) extubation following emergence and (ii) discharge from the post-anesthesia care unit. Adjustments were made in the dosages of premedication (midazolam) and opioid analgesic administered following induction (hydromorphone) depending on the severity of OSA. A non-validated but fixed anesthesia protocol tailored to the severity of OSA was used in all patients. In addition, all adverse events were also monitored. RESULTS A paradoxical, yet significant reduction in emergence time was observed among patients with severe OSA following surgery (ANOVA, Tukey-Kramer post hoc tests, P<0.001). There were also fewer adverse events in this group. CONCLUSIONS Emergence from anesthesia after adenotonsillectomy may be positively influenced by an anesthetic technique titrated according to the severity of OSA. Adverse respiratory events due to the severity of sleep apnea and attendant hypoxemia may be minimized and outcomes improved with similarly tailored protocols.

Tracheostomy for Severe Pediatric Obstructive Sleep Apnea: Indications and Outcomes

Objectives (1) To describe characteristics of pediatric patients undergoing tracheostomy for obstructive sleep apnea (OSA). (2) To highlight perioperative events and outcomes of the procedure. Study Design Case series with chart review. Setting Four tertiary care academic children’s hospitals. Subjects and Methods Twenty-nine children aged <18 years from January 1, 2010, to December 31, 2015, who underwent tracheostomy for severe OSA, defined as an apnea-hypopnea index (AHI) >10, were included in the study. Data on patient characteristics, polysomnographic findings, comorbidities, and perioperative events and outcomes were collected and analyzed. Results Twenty-nine patients were included. Mean age at tracheostomy was 2.0 years (95% CI, −2.2 to 6.2). Mean body mass index z score was −1.2 (95% CI, −4.9 to −2.5). Mean preoperative AHI was 60.2 (95% CI, −15.7 to 136.1). Mean postoperative intensive care unit stay was 23.2 days (95% CI, 1.44-45.0). One procedure was complicated by bronchospasm. Thirteen patients had craniofacial abnormalities; 10 had a neurologic disorder resulting in hypotonia; and 5 had a diagnosis of laryngomalacia. Mean follow-up was 30.6 months (95% CI, −10.4 to 71.6). Six patients were decannulated, with a mean time to decannulation of 40.8 months (95% CI, 7.9-73.7). Five patients underwent capped sleep study prior to decannulation with a mean AHI of 6.6 (95% CI, −9.9 to 23.1) and a mean oxygen nadir of 90.0% (95% CI, 80%-100%). Conclusion OSA is an uncommon indication for tracheostomy in children. Patients who require the procedure usually have an associated syndromic diagnosis resulting in upper airway obstruction. The majority of children who undergo tracheostomy for OSA will remain dependent at 24 months.

Envelope enhancement increases cortical sensitivity to interaural envelope delays with acoustic and electric hearing.

Evidence from human psychophysical and animal electrophysiological studies suggests that sensitivity to interaural time delay (ITD) in the modulating envelope of a high-frequency carrier can be enhanced using half-wave rectified stimuli. Recent evidence has shown potential benefits of equivalent electrical stimuli to deaf individuals with bilateral cochlear implants (CIs). In the current study we assessed the effects of envelope shape on ITD sensitivity in the primary auditory cortex of normal-hearing ferrets, and profoundly-deaf animals with bilateral CIs. In normal-hearing animals, cortical sensitivity to ITDs (±1 ms in 0.1-ms steps) was assessed in response to dichotically-presented i) sinusoidal amplitude-modulated (SAM) and ii) half-wave rectified (HWR) tones (100-ms duration; 70 dB SPL) presented at the best-frequency of the unit over a range of modulation frequencies. In separate experiments, adult ferrets were deafened with neomycin administration and bilaterally-implanted with intra-cochlear electrode arrays. Electrically-evoked auditory brainstem responses (EABRs) were recorded in response to bipolar electrical stimulation of the apical pair of electrodes with singe biphasic current pulses (40 µs per phase) over a range of current levels to measure hearing thresholds. Subsequently, we recorded cortical sensitivity to ITDs (±800 µs in 80-µs steps) within the envelope of SAM and HWR biphasic-pulse trains (40 µs per phase; 6000 pulses per second, 100-ms duration) over a range of modulation frequencies. In normal-hearing animals, nearly a third of cortical neurons were sensitive to envelope-ITDs in response to SAM tones. In deaf animals with bilateral CI, the proportion of ITD-sensitive cortical neurons was approximately a fifth in response to SAM pulse trains. In normal-hearing and deaf animals with bilateral CI the proportion of ITD sensitive units and neural sensitivity to ITDs increased in response to HWR, compared with SAM stimuli. Consequently, novel stimulation strategies based on envelope enhancement may prove beneficial to individuals with bilateral cochlear implants.

Current Trends in Neonatal Tracheostomy.

IMPORTANCE The indications for neonatal tracheostomy may have changed with current noninvasive respiratory therapies compared with previous decades. OBJECTIVES To study the current trends in neonatal tracheostomy and identify the primary indication for the procedure and risk factors for failed extubation. DESIGN, SETTING, AND PARTICIPANTS This retrospective medical record review included 47 neonates who underwent tracheostomy from January 1, 2009, to December 31, 2013, at the University of Maryland Childrens Hospital. Group 1 included infants undergoing tracheostomy for the primary indication of upper airway obstruction; group 2, infants with primary pulmonary disease. Data on weight, gestational age, comorbid conditions, congenital abnormalities, complications, outcomes, and indications for tracheostomy were compared statistically between groups. MAIN OUTCOMES AND MEASURES Differences in gestational age, birth weight, and age at tracheostomy. RESULTS Among the 47 infants included in the study (30 boys; 17 girls, mean [SD] age, 113 [73] days), 31 (66%) demonstrated anatomical causes of airway obstruction, and 16 (34%) had significant pulmonary disease. Among infants with anatomical causes, subglottic stenosis represented the largest group (11 of 31 [35%]). The mean age at the time of tracheostomy was significantly lower in the group with airway obstruction (98.9 vs 146.9 days; difference, 48 [95% CI, 4.8-91.2] days; P = .04). No procedure-related morbidity or mortality was encountered. CONCLUSIONS AND RELEVANCE Anatomical upper airway obstruction may be returning as the most common indication for a neonatal tracheostomy, thereby supporting the belief that current respiratory therapies have lowered the burden of chronic lung disease and the need for prolonged ventilatory care.

Assessment of a Novel Computer Algorithm for Printing a 3-Dimensional Nasal Prosthetic

Importance The introduction and evaluation of a novel technique to create nasal prostheses with 3-dimensional (3-D) imaging software may circumvent the need for an anaplastologist. Objectives To describe a novel computer algorithm for the creation of a 3-D model of a nose and to evaluate the similarity of appearance of the nasal prosthesis with that of the individual’s nose. Design, Setting, and Participants A prospective pilot study with a cross-sectional survey was conducted from August 1 to October 31, 2016, at a tertiary care academic center. Five volunteers were used for creation of the nasal prostheses, and 36 survey respondents with a medical background were involved in evaluating the nasal prostheses. Exposures A computer algorithm using a 3-D animation software (Blender; Blender Foundation) and Adobe Photoshop CS6 (Adobe Systems) were used to create a 3-D model of a nose. Photographs of 5 volunteers were processed with the computer algorithm. The model was then printed using a desktop 3-D printer. Attending physicians, residents, and medical students completed a survey and were asked to rate the similarity between the individuals’ photographs and their 3-D printed nose on a Likert-type scale. Main Outcomes and Measures The similarity between 3-D printed nasal models and photographs of the volunteers’ noses based on survey data. Results Thirty-six survey respondents evaluated 4 views for each of the 5 modeled noses (from 4 women and 1 man; mean [SD] age, 26.6 [5.7] years). The mean (SD) score for the overall similarity between the photographs and the 3-D models was 8.42 (1.34). The mean scores for each nasal comparison ranged from 7.97 to 8.62. According to the survey, respondents were able to match the correct 3-D nose to the corresponding volunteers’ photographs in 171 of 175 photographs (97.7%). All surveyed clinicians indicated that they would consider using this tool to create a temporary prosthesis instead of referring to a prosthodontist. Conclusions and Relevance This algorithm can be used to model and print a 3-D prosthesis of a human nose. The printed models closely depicted the photographs of each volunteer’s nose and can potentially be used to create a temporary prosthesis to fill external nasal defects. The appropriate clinical application of this technique is yet to be determined.

Very Severe Obstructive Sleep Apnea in Children: Outcomes of Adenotonsillectomy and Risk Factors for Persistence

Objectives (1) To describe the clinical, demographic and polysomnographic (PSG) characteristics of children with very severe obstructive sleep apnea (OSA) without significant comorbidities; (2) to assess the outcomes following tonsillectomy and adenoidectomy (T&A); and (3) to determine predictors of persistence of OSA after T&A. Study Design Case series with chart review. Setting Tertiary-level freestanding children’s hospital. Subjects and Methods Seventy-four children aged 2 to 12 years who underwent T&A for very severe OSA (obstructive apnea-hypopnea index [AHI] >30) were included. Children with significant comorbidities were excluded. PSG variables were compared pre- and post-T&A using statistical tests. Factors affecting OSA resolution and persistence were studied. Results The mean (95% confidence interval) age was 4.3 (3.8-4.7) years with the majority black or Hispanic (64/74, 86%). The mean decrease in AHI after T&A was 49 (43-58) (P < .001). Complete resolution of OSA, defined by an AHI <1, or an AHI <5 was seen in 32% (24/74) and 80% (59/74), respectively. Total sleep time (TST) greater than 5 minutes with end-tidal CO2 >50 mm Hg was strongly associated with persistent OSA. The decrease in AHI post-T&A was best predicted by higher preoperative oxygen saturation (SpO2) nadir and lower TST with SpO2 <90% (R 2 = 0.24, P < .001). Conclusions T&A is associated with a significant improvement but not resolution of very severe OSA. The severity of baseline hypercapnia and hypoxemia may best predict persistent OSA after T&A. The study supports obtaining routine post-T&A PSG in children with very severe OSA.