Publication date: Available online 27 June 2017
Author(s): Peter Heil, Artur Matysiak, Heinrich Neubauer
Thresholds for detecting sounds in quiet decrease with increasing sound duration in every species studied. The neural mechanisms underlying this trade-off, often referred to as temporal integration, are not fully understood. Here, we probe the human auditory system with a large set of tone stimuli differing in duration, shape of the temporal amplitude envelope, duration of silent gaps between bursts, and frequency. Duration was varied by varying the plateau duration of plateau-burst (PB) stimuli, the duration of the onsets and offsets of onset-offset (OO) stimuli, and the number of identical bursts of multiple-burst (MB) stimuli. Absolute thresholds for a large number of ears (>230) were measured using a 3-interval-3-alternative forced choice (3I-3AFC) procedure. Thresholds decreased with increasing sound duration in a manner that depended on the temporal envelope. Most commonly, thresholds for MB stimuli were highest followed by thresholds for OO and PB stimuli of corresponding durations. Differences in the thresholds for MB and OO stimuli and in the thresholds for MB and PB stimuli, however, varied widely across ears, were negative in some ears, and were tightly correlated. We show that the variation and correlation of MB-OO and MB-PB threshold differences are linked to threshold microstructure, which affects the relative detectability of the sidebands of the MB stimuli and affects estimates of the bandwidth of auditory filters. We also found that thresholds for MB stimuli increased with increasing duration of the silent gaps between bursts. We propose a new model and show that it accurately accounts for our results and does so considerably better than a leaky-integrator-of-intensity model and a probabilistic model proposed by others. Our model is based on the assumption that sensory events are generated by a Poisson point process with a low rate in the absence of stimulation and higher, time-varying rates in the presence of stimulation. A subject in a 3I-3AFC task is assumed to choose the interval in which the greatest number of events occurred or randomly chooses among intervals which are tied for the greatest number of events. The subject is further assumed to count events over the duration of an evaluation interval that has the same timing and duration as the expected stimulus. The increase in the rate of the events caused by stimulation is proportional to the time-varying amplitude envelope of the bandpass-filtered signal raised to an exponent. We find the exponent to be ∼3, consistent with our previous studies. This challenges models that are based on the assumption of the integration of a neural response that is directly proportional to the stimulus amplitude or proportional to its square (i.e., proportional to the stimulus intensity or power).
This study aimed to improve understanding of speech characteristics associated with dysarthria in children with cerebral palsy by analyzing segmental and global formant measures in single-word and sentence contexts.
Ten 5-year-old children with cerebral palsy and dysarthria and 10 age-matched, typically developing children participated in this study. Vowel space area and second formant interquartile range were measured from children’s elicited productions of single words and sentences.
Results showed that the children with dysarthria had significantly smaller vowel space areas than typically developing children in both word and sentence contexts; however, overall ranges of second formant movement did not differ between groups in word or sentence contexts. Additional analysis of single words revealed that, compared to typical children, children with dysarthria had smaller second formant interquartile ranges in single words with phonetic contexts requiring large changes in vocal tract configuration, but not in single words with monophthongs.
Results of this study suggest that children with dysarthria may not have globally reduced ranges of articulatory movement compared to typically developing peers; however, they do exhibit reduced precision in producing phonetic targets.
Early hematopoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up.
Mol Genet Metab Rep. 2017 Sep;12:62-68
Authors: Barth AL, de Magalhães TSPC, Reis ABR, de Oliveira ML, Scalco FB, Cavalcanti NC, Silva DSE, Torres DA, Costa AAP, Bonfim C, Giugliani R, Llerena JC, Horovitz DDG
Mucopolysaccharidosis type II (MPS II – Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2 sulfatase (I2S), leading to the accumulation of the glycosaminoglycans, affecting multiple organs and systems. Enzyme replacement therapy does not cross the blood brain barrier, limiting results in neurological forms of the disease. Another option of treatment for severe MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS type I, since it can preserve neurocognition when performed early in the course of the disease. To date, only few studies have examined the long-term outcomes of HSCT in patients with MPS II. We describe the seven-year follow-up of a prenatally diagnosed MPS II boy with positive family history of severe MPS form, submitted to HSCT with umbilical cord blood cells at 70 days of age. Engraftment after 30 days revealed mixed chimerism with 79% donor cells; after 7 years engraftment remains at 80%. I2S activity 30 days post-transplant was low in plasma and normal in leukocytes and the same pattern is observed to date. At age 7 years growth charts are normal and he is very healthy, although mild signs of dysostosis multiplex are present, as well as hearing loss. The neuropsychological evaluation (Wechsler Intelligence Scale for Children – Fourth Edition – WISC-IV), disclosed an IQ of 47. Despite this low measured IQ, the patient continues to show improvements in cognitive, language and motor skills, being quite functional. We believe that HSCT is a therapeutic option for MPS II patients with the severe phenotype, as it could preserve neurocognition or even halt neurodegeneration, provided strict selection criteria are followed.
PMID: 28649514 [PubMed – in process]
Cost-effectiveness of Universal and Targeted Newborn Screening for Congenital Cytomegalovirus Infection.
JAMA Pediatr. 2016 Dec 01;170(12):1173-1180
Authors: Gantt S, Dionne F, Kozak FK, Goshen O, Goldfarb DM, Park AH, Boppana SB, Fowler K
Importance: Congenital cytomegalovirus (cCMV) infection is a major cause of childhood deafness. Most cCMV infections are not diagnosed without newborn screening, resulting in missed opportunities for directed care.
Objective: To estimate the cost-effectiveness of universal and targeted newborn cCMV screening programs compared with no cCMV screening.
Design, Setting, and Participants: Models were constructed using rates and outcomes from prospective cohort studies of newborn cCMV screening in US postpartum care and early hearing programs. Costs of laboratory testing, treatment, and hearing loss were drawn from Medicaid data and published estimates. The benefits of cCMV screening were assumed to come from antiviral therapy for affected newborns to reduce hearing loss and from earlier identification of hearing loss with postnatal onset. Analyses were performed from July 2014 to March 2016.
Interventions: Models compared universal or targeted cCMV screening of newborns with a failed hearing screen, with standard care for cCMV infection.
Main Outcomes and Measures: The incremental costs of identifying 1 cCMV infection, identifying 1 case of cCMV-related hearing loss, and preventing 1 cochlear implant; the incremental reduction in cases of severe to profound hearing loss; and the differences in costs per infant screened by universal or targeted strategies under different assumptions about the effectiveness of antiviral treatment.
Results: Among all infants born in the United States, identification of 1 case of cCMV infection by universal screening was estimated to cost $2000 to $10 000; by targeted screening, $566 to $2832. The cost of identifying 1 case of hearing loss due to cCMV was as little as $27 460 by universal screening or $975 by targeted screening. Assuming a modest benefit of antiviral treatment, screening programs were estimated to reduce severe to profound hearing loss by 4.2% to 13% and result in direct costs of $10.86 per newborn screened. However, savings of up to $37.97 per newborn screened were estimated when costs related to functionality were included.
Conclusions and Relevance: Newborn screening for cCMV infection appears to be cost-effective under a wide range of assumptions. Universal screening offers larger net savings and the greatest opportunity to provide directed care. Targeted screening also appears to be cost-effective and requires testing for fewer newborns. These findings suggest that implementation of newborn cCMV screening programs is warranted.
PMID: 27723885 [PubMed – indexed for MEDLINE]
Smartphone hearing screening in mHealth assisted community-based primary care.
J Telemed Telecare. 2016 Oct;22(7):405-12
Authors: Yousuf Hussein S, Wet Swanepoel D, Biagio de Jager L, Myburgh HC, Eikelboom RH, Hugo J
INTRODUCTION: Access to ear and hearing health is a challenge in developing countries, where the burden of disabling hearing loss is greatest. This study investigated community-based identification of hearing loss using smartphone hearing screening (hearScreen™) operated by community health workers (CHWs) in terms of clinical efficacy and the reported experiences of CHWs.
METHOD: The study comprised two phases. During phase one, 24 CHWs performed community-based hearing screening as part of their regular home visits over 12 weeks in an underserved community, using automated test protocols employed by the hearScreen™ smartphone application, operating on low-cost smartphones with calibrated headphones. During phase two, CHWs completed a questionnaire regarding their perceptions and experiences of the community-based screening programme.
RESULTS: Data analysis was conducted on the results of 108 children (2-15 years) and 598 adults (16-85 years). Referral rates for children and adults were 12% and 6.5% respectively. Noise exceeding permissible levels had a significant effect on screen results at 25 dB at 1 kHz (p<0.05). Age significantly affected adult referral rates (p < 0.05), demonstrating a lower rate (4.3%) in younger as opposed to older adults (13.2%). CHWs were positive regarding the hearScreen™ solution in terms of usability, need for services, value to community members and time efficiency.
CONCLUSION: Smartphone-based hearing screening allows CHWs to bring hearing health care to underserved communities at a primary care level. Active noise monitoring and data management features allow for quality control and remote monitoring for surveillance and follow-up.
PMID: 26468215 [PubMed – indexed for MEDLINE]
Publication date: September 2017
Source:Gait & Posture, Volume 57
Author(s): Andrea L. Rosso, Massimo Cenciarini, Patrick J. Sparto, Patrick J. Loughlin, Joseph M. Furman, Theodore J. Huppert
Cognitive tasks impact postural control when performed concurrently as dual-tasks. This is presumed to result from capacity limitations in relevant brain regions. We used functional near-infrared spectroscopy (fNIRS) to measure brain activation of the left motor, temporal, and dorsal-lateral prefrontal brain regions of younger (n=6) and older (n=10) adults. Brain activation was measured during an auditory choice reaction task (CRT) and standing on a dynamic posturography platform, both as single-tasks and concurrently as dual-task. Body sway was assessed by median absolute deviation (MAD) of anterior-posterior translation of the center of mass (COM). Brain activation was measured as changes in oxy-hemoglobin by fNIRS. During both single- and dual-task conditions, we found that older adults had greater brain activation relative to younger adults. During dual task performance, the total activation was less than expected from the sum of individual conditions for both age groups, indicating a dual-task interference (reduction in younger adults=53% [p=0.02]; in older adults=53%; [p=0.008]). This reduction was greater for the activation attributable to the postural task (reduction younger adults=75% [p=0.03]; older adults=59% [p=0.005]) compared to the CRT task (reduction younger adults=10%, [p=0.6]; older adults=7.3%, [p=0.5]) in both age groups. Activation reduction was not accompanied by any significant changes in body sway in either group (older adults: single-task MAD=0.94cm, dual-task MAD=1.10cm, p=0.20; younger adults: single-task RMS=0.95cm, dual-task MAD=1.08cm, p=0.14). Our results indicate that neural resources devoted to postural control are reduced under dual-task conditions that engage attention.
Objectives: This systematic review aimed to investigate the prevalence and characteristics of vestibular adverse effects of aminoglycoside (AG) therapy in humans and to analyze objective vestibular tests for the detection of AG-induced vestibulotoxicity.
Design: PubMed, Cochrane Database, Web of Science, and reference lists of all included studies were screened by two independent researchers. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Studies were included according to preset inclusion criteria and reported outcomes of studies evaluating vestibular function using one or more objective vestibular function tests in adults and children after systemic AG administration. The methodological quality of each study was assessed using the quality assessment tool for quantitative studies. Interrater reliability was established using Cohen’s Kappa.
Results: Twenty-seven studies were included, with the vast majority showing AG-induced vestibulotoxic side effects, ranging from 0 to 60%. Most studies reported AG-induced abnormalities by caloric and rotatory testing, whereas only a few studies reported using video Head Impulse test and vestibular evoked myogenic potential testing.
Conclusions: Because type I hair cells (particularly of the semicircular canals) are more susceptible to ototoxicity, video Head Impulse test and vestibular evoked myogenic potential testing seem more promising for the early detection of vestibulotoxicity than caloric and rotatory testing. Prospective studies using an extensive vestibular test battery are needed to further characterize the impact of AGs on the different vestibular end organs and to identify the most sensitive vestibular technique for the early detection of vestibulotoxicity.
Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
<p>Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child’s most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.</p>
<p>We have developed a technique based on low-coherence interferometry—a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum—to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.</p><br /><br />
Identification of a novel splicing mutation within SLC17A8 in a Korean family with hearing loss by whole-exome sequencing.
Gene. 2017 Jun 21;:
Authors: Ryu N, Lee S, Park HJ, Lee B, Kwon TJ, Bok J, Park CI, Lee KY, Baek JI, Kim UK
Hereditary hearing loss (HHL) is a common genetically heterogeneous disorder, which follows Mendelian inheritance in humans. Because of this heterogeneity, the identification of the causative gene of HHL by linkage analysis or Sanger sequencing have shown economic and temporal limitations. With recent advances in next-generation sequencing (NGS) techniques, rapid identification of a causative gene via massively parallel sequencing is now possible. We recruited a Korean family with three generations exhibiting autosomal dominant inheritance of HL, and the clinical information about this family revealed that there are no other symptoms accompanied with HL. To identify a causative mutation of HL in this family, we performed whole-exome sequencing of 4 family members, 3 affected and an unaffected. As the result, A novel splicing mutation, c.763+1G>T, in the solute carrier family 17, member 8 (SLC17A8) gene was identified in the patients, and the genotypes of the mutation were co-segregated with the phenotype of HL. Additionally, this mutation was not detected in 100 Koreans with normal hearing. Via NGS, we detected a novel splicing mutation that might influence the hearing ability within the patients with autosomal dominant non-syndromic HL. Our data suggests that this technique is a powerful tool to discover causative genetic factors of HL and facilitate diagnoses of the primary cause of HHL.
PMID: 28647561 [PubMed – as supplied by publisher]
Fever-Induced Paroxysmal Weakness and Encephalopathy, a New Phenotype of ATP1A3 Mutation.
Pediatr Neurol. 2017 Apr 29;:
Authors: Yano ST, Silver K, Young R, DeBrosse SD, Ebel RS, Swoboda KJ, Acsadi G
BACKGROUND: We identified a group of patients with ATP1A3 mutations at residue 756 who display a new phenotype, distinct from alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndromes.
METHODS: Four patients with c.2267G>A (R756H) mutations from two families and two patients with c.2267G>T (R756L) mutations from one family are described and compared with the previously reported patients with mutations resulting in R756H and R756C protein variants.
RESULTS: Patients with ATP1A3 R756H have onset in childhood of infrequent, fever-triggered paroxysms of encephalopathy and weakness with slowly improving but persistent deficits. Motor findings of weakness are mostly generalized, and patients may also have bulbar or oculomotor problems. Longer-term outcomes range from mild motor apraxia with near-normal function to persistent dysphagia, dysarthria, cognitive deficit, motor apraxia, and inability to walk because of ataxia. Patients with ATP1A3 R756L have a similar phenotype that includes paroxysmal, stepwise progression of ataxia associated with infections.
CONCLUSIONS: ATP1A3 mutations affecting residue 756 result in a clinical syndrome, separate from those associated with previously described ATP1A3 mutations, which consists chiefly of fever-induced paroxysmal weakness and encephalopathy (FIPWE). Patients with R756L and R756C protein variants display more prominent ataxia, overlapping with the relapsing encephalopathy with cerebellar ataxia syndrome previously described in a patient with the c.2266C>T (R756C) mutation. All patients reported with mutations at residue 756 to date have had a similar episodic course and clinical features. Patients with mutations of ATP1A3 residue 756 appear to have a distinct clinical phenotype compared with patients with other ATP1A3 mutations, with fever-induced encephalopathy as key differentiating feature.
PMID: 28647130 [PubMed – as supplied by publisher]