Binaural Fusion and Listening Effort in Children Who Use Bilateral Cochlear Implants: A Psychoacoustic and Pupillometric Study

Bilateral cochlear implants aim to provide hearing to both ears for children who are deaf and promote binaural/spatial hearing. Benefits are limited by mismatched devices and unilaterally-driven development which could compromise the normal integration of left and right ear input. We thus asked whether children hear a fused image (ie. 1 vs 2 sounds) from their bilateral implants and if this “binaural fusion” reduces listening effort. Binaural fusion was assessed by asking 25 deaf children with cochlear implants and 24 peers with normal hearing whether they heard one or two sounds when listening to bilaterally presented acoustic click-trains/electric pulses (250 Hz trains of 36 ms presented at 1 Hz). Reaction times and pupillary changes were recorded simultaneously to measure listening effort. Bilaterally implanted children heard one image of bilateral input less frequently than normal hearing peers, particularly when intensity levels on each side were balanced. Binaural fusion declined as brainstem asymmetries increased and age at implantation decreased. Children implanted later had access to acoustic input prior to implantation due to progressive deterioration of hearing. Increases in both pupil diameter and reaction time occurred as perception of binaural fusion decreased. Results indicate that, without binaural level cues, children have difficulty fusing input from their bilateral implants to perceive one sound which costs them increased listening effort. Brainstem asymmetries exacerbate this issue. By contrast, later implantation, reflecting longer access to bilateral acoustic hearing, may have supported development of auditory pathways underlying binaural fusion. Improved integration of bilateral cochlear implant signals for children is required to improve their binaural hearing.     

Development of Sound Localization Strategies in Children with Bilateral Cochlear Implants

Localizing sounds in our environment is one of the fundamental perceptual abilities that enable humans to communicate, and to remain safe. Because the acoustic cues necessary for computing source locations consist of differences between the two ears in signal intensity and arrival time, sound localization is fairly poor when a single ear is available. In adults who become deaf and are fitted with cochlear implants (CIs) sound localization is known to improve when bilateral CIs (BiCIs) are used compared to when a single CI is used. The aim of the present study was to investigate the emergence of spatial hearing sensitivity in children who use BiCIs, with a particular focus on the development of behavioral localization patterns when stimuli are presented in free-field horizontal acoustic space. A new analysis was implemented to quantify patterns observed in children for mapping acoustic space to a spatially relevant perceptual representation. Children with normal hearing were found to distribute their responses in a manner that demonstrated high spatial sensitivity. In contrast, children with BiCIs tended to classify sound source locations to the left and right; with increased bilateral hearing experience, they developed a perceptual map of space that was better aligned with the acoustic space. The results indicate experience-dependent refinement of spatial hearing skills in children with CIs. Localization strategies appear to undergo transitions from sound source categorization strategies to more fine-grained location identification strategies. This may provide evidence for neural plasticity, with implications for training of spatial hearing ability in CI users.     

Neural Correlates of Speech Processing in Prelingually Deafened Children and Adolescents with Cochlear Implants

Prelingually deafened children with cochlear implants stand a good chance of developing satisfactory speech performance. Nevertheless, their eventual language performance is highly variable and not fully explainable by the duration of deafness and hearing experience. In this study, two groups of cochlear implant users (CI groups) with very good basic hearing abilities but non-overlapping speech performance (very good or very bad speech performance) were matched according to hearing age and age at implantation. We assessed whether these CI groups differed with regard to their phoneme discrimination ability and auditory sensory memory capacity, as suggested by earlier studies. These functions were measured behaviorally and with the Mismatch Negativity (MMN). Phoneme discrimination ability was comparable in the CI group of good performers and matched healthy controls, which were both better than the bad performers. Source analyses revealed larger MMN activity (155–225 ms) in good than in bad performers, which was generated in the frontal cortex and positively correlated with measures of working memory. For the bad performers, this was followed by an increased activation of left temporal regions from 225 to 250 ms with a focus on the auditory cortex. These results indicate that the two CI groups developed different auditory speech processing strategies and stress the role of phonological functions of auditory sensory memory and the prefrontal cortex in positively developing speech perception and production.     

Speech Perception and Localisation with SCORE Bimodal: A Loudness Normalisation Strategy for Combined Cochlear Implant and Hearing Aid Stimulation

A significant fraction of newly implanted cochlear implant recipients use a hearing aid in their non-implanted ear. SCORE bimodal is a sound processing strategy developed for this configuration, aimed at normalising loudness perception and improving binaural loudness balance. Speech perception performance in quiet and noise and sound localisation ability of six bimodal listeners were measured with and without application of SCORE. Speech perception in quiet was measured either with only acoustic, only electric, or bimodal stimulation, at soft and normal conversational levels. For speech in quiet there was a significant improvement with application of SCORE. Speech perception in noise was measured for either steady-state noise, fluctuating noise, or a competing talker, at conversational levels with bimodal stimulation. For speech in noise there was no significant effect of application of SCORE. Modelling of interaural loudness differences in a long-term-average-speech-spectrum-weighted click train indicated that left-right discrimination of sound sources can improve with application of SCORE. As SCORE was found to leave speech perception unaffected or to improve it, it seems suitable for implementation in clinical devices.     

HOMER2, a Stereociliary Scaffolding Protein,Is Essential for Normal Hearing in Humans and Mice

Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS) the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL). After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in HOMER2, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 HOMER2 mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action.     

Intermuscular Coherence in Normal Adults: Variability and Changes with Age

We investigated beta-band intermuscular coherence (IMC) in 92 healthy adults stratified by decade of age, and analysed variability between and within subjects. In the dominant upper limb, IMC was estimated between extensor digitorum communis and first dorsal interosseous as well as between flexor digitorum superficialis and first dorsal interosseous. In the ipsilateral lower limb, IMC was measured between medial gastrocnemius and extensor digitorum brevis as well as between tibialis anterior and extensor digitorum brevis. Age-related changes in IMC were analysed with age as a continuous variable or binned by decade. Intrasession variance of IMC was examined by dividing sessions into pairs of epochs and comparing coherence estimates between these pairs. Eight volunteers returned for a further session after one year, allowing us to compare intrasession and intersession variance. We found no age-related changes in IMC amplitude across almost six decades of age, allowing us to collate data from all ages into an aggregate normative dataset. Interindividual variability ranged over two orders of magnitude. Intrasession variance was significantly greater than expected from statistical variability alone, and intersession variance was even larger. Potential contributors include fluctuations in task performance, differences in electrode montage and short-term random variation in central coupling. These factors require further exploration and, where possible, minimisation. This study provides evidence that coherence is remarkably robust to senescent changes in the nervous system and provides a large normative dataset for future applications of IMC as a biomarker in disease states.     

Carrier Status for the Common R501X and 2282del4 Filaggrin Mutations Is Not Associated with Hearing Phenotypes in 5377 Children from the ALSPAC Cohort

Background

Filaggrin is a major protein in the epidermis. Several mutations in the filaggrin gene (FLG) have been associated with a number of conditions. Filaggrin is expressed in the tympanic membrane and could alter its mechanical properties, but the relationship between genetic variation in FLG and hearing has not yet been tested.

Methodology/Principal Findings

We examined whether loss-of function mutations R501X and 2282del4 in the FLG gene affected hearing in children. Twenty eight hearing variables representing five different aspects of hearing at age nine years in 5,377 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort were tested for association with these mutations. No evidence of association was found between R501X or 2282del4 (or overall FLG mutation carrier status) and any of the hearing phenotypes analysed.

Conclusions/Significance

In conclusion, carrier status for common filaggrin mutations does not affect hearing in children.     

Evidence in Obese Children: Contribution of Hyperlipidemia,Obesity-Inflammation,and Insulin Sensitivity

Background

Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children.

Methods

We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits.

Results

Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%).

Conclusions

Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.     

Role of VEGF Receptors in Normal and Psoriatic Human Keratinocytes: Evidence from Irradiation with Different UV Sources

Vascular endothelial growth factor (VEGF) promotes angiogenesis and plays important roles both in physiological and pathological conditions. VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and are originally considered specific to endothelial cells. We previously reported that VEGFRs were also constitutively expressed in normal human keratinocytes and overexpressed in psoriatic epidermis. In addition, UVB can activate VEGFRs in normal keratinocytes, and the activated VEGFR-2 signaling is involved in the pro-survival mechanism. Here, we show that VEGFRs were also upregulated and activated by UVA in normal human keratinocytes via PKC, and interestingly, both the activated VEGFR-1 and VEGFR-2 protected against UVA-induced cell death. As VEGFRs were over-expressed in psoriatic epidermis, we further investigated whether narrowband UVB (NB-UVB) phototherapy or topical halomethasone monohydrate 0.05% cream could affect their expression. Surprisingly, the over-expressed VEGFRs in psoriatic epidermis were significantly attenuated by both treatments. During NB-UVB therapy, VEGFRs declined first in the basal, and then gradually in the upper psoriatic epidermis. VEGFRs were activated in psoriatic epidermis, their activation was enhanced by NB-UVB, but turned undetectable after whole therapy. This process was quite different from that by halomethasone, in which VEGFRs and phospho-VEGFRs decreased in a gradual, homogeneous manner. Our findings further suggest that UV-induced activation of VEGFRs serves as a pro-survival signal for keratinocytes. In addition, VEGFRs may be involved in the pathological process of psoriasis, and UV phototherapy is effective for psoriasis by directly modulating the expression of VEGFRs.     

Hospital Admissions in Children with Down Syndrome: Experience of a Population-Based Cohort Followed from Birth

Objective

Children with Down syndrome, the most common genetic cause of intellectual disability, are prone to multiple and varied health-related problems. This study describes patterns of hospitalisations for children and young people with Down syndrome in Western Australia.

Methods

Birth records were linked to the Western Australian population-based Intellectual Disability database to identify all children born with Down syndrome in Western Australia between 1 January, 1983 and 31 December, 1999. These records were linked to the Hospital Morbidity Data System to provide information on all hospitalisations up to 31 December, 2004. Hospitalisation data, coded using ICD-9CM or ICD-10 (v0.5) were grouped into clinically relevant categories using the primary diagnosis. Rates of hospital admission for all and specific diagnoses were expressed in 1000-person-years at-risk and median age at first admission and length of stay were calculated.

Results

Of the 405 children, 395 had one or more hospital admissions, totalling 3786 admissions for all children and an estimated 39.5 person-years in hospital. On average, children were admitted 9.7 times, with an estimated rate of 757.2 admissions per 1000pyr (95% CI: 680, 843). A quarter of all admissions occurred in the first year of life. The average hospital length of stay was 3.8 days (95% CI: 3.7, 4.1). Upper respiratory tract conditions affected the most children (58.5%) and accounted for 12.1% of all admissions. Other disorders which affected a high percentage of children were ear/hearing conditions (50.6%), disorders of the oral cavity (38.0%) and lower respiratory tract conditions (37.5%). Overall, children with Down syndrome were hospitalised at a rate five times (95% CI = 4.3–6.2) that of the general population.

Conclusion

Children with Down syndrome are at increased risk of morbidity for varied causes underlining the importance of comprehensive and targeted primary care for this group.     

Changes of Blood Pressure,Renin, and Angiotensin after Bilateral Nephrectomy in Patients with Chronic Renal Failure

Circulating levels of renin, angiotensin I, and angiotensin II were increased in six patients with chronic renal failure and hypertension uncontrolled by dialysis and hypotensive drugs. Lower and often normal levels were found in 10 patients whose blood pressure was controlled by dialysis treatment. For a variety of reasons all patients were subjected to bilateral nephrectomy. The logarithm of the decrease in plasma concentrations of renin and angiotensin II was significantly related to the fall of blood pressure after operation. Plasma renin concentration correlated significantly with blood angiotensin I concentration and with plasma angiotensin II in samples taken before and after nephrectomy. Renin, angiotensin I, and angiotensin II were measurable in samples of blood taken 48 hours or more after the operation.     

Normal Weight Obesity Is Associated with Metabolic Syndrome and Insulin Resistance in Young Adults from a Middle-Income Country

Objective

This population-based birth cohort study examined whether normal weight obesity is associated with metabolic disorders in young adults in a middle-income country undergoing rapid nutrition transition.

Design and Methods

The sample involved 1,222 males and females from the 1978/79 Ribeirão Preto birth cohort, Brazil, aged 23–25 years. NWO was defined as body mass index (BMI) within the normal range (18.5–24.9 kg/m²) and the sum of subscapular and triceps skinfolds above the sex-specific 90th percentiles of the study sample. It was also defined as normal BMI and % BF (body fat) >23% in men and >30% in women. Insulin resistance (IR), insulin sensitivity and secretion were based on the Homeostasis Model Assessment (HOMA) model.

Results

In logistic models, after adjusting for age, sex and skin colour, NWO was significantly associated with Metabolic Syndrome (MS) according to the Joint Interim Statement (JIS) definition (Odds Ratio OR = 6.83; 95% Confidence Interval CI 2.84–16.47). NWO was also associated with HOMA2-IR (OR = 3.81; 95%CI 1.57–9.28), low insulin sensitivity (OR = 3.89; 95%CI 2.39–6.33), and high insulin secretion (OR = 2.17; 95%CI 1.24–3.80). Significant associations between NWO and some components of the MS were also detected: high waist circumference (OR = 8.46; 95%CI 5.09–14.04), low High Density Lipoprotein cholesterol (OR = 1.65; 95%CI 1.11–2.47) and high triglyceride levels (OR = 1.93; 95%CI 1.02–3.64). Most estimates changed little after further adjustment for early and adult life variables.

Conclusions

NWO was associated with MS and IR, suggesting that clinical assessment of excess body fat in normal-BMI individuals should begin early in life even in middle-income countries.     

Transmission of Facial Expressions of Emotion Co-Evolved with Their Efficient Decoding in the Brain: Behavioral and Brain Evidence

Competent social organisms will read the social signals of their peers. In primates, the face has evolved to transmit the organism''s internal emotional state. Adaptive action suggests that the brain of the receiver has co-evolved to efficiently decode expression signals. Here, we review and integrate the evidence for this hypothesis. With a computational approach, we co-examined facial expressions as signals for data transmission and the brain as receiver and decoder of these signals. First, we show in a model observer that facial expressions form a lowly correlated signal set. Second, using time-resolved EEG data, we show how the brain uses spatial frequency information impinging on the retina to decorrelate expression categories. Between 140 to 200 ms following stimulus onset, independently in the left and right hemispheres, an information processing mechanism starts locally with encoding the eye, irrespective of expression, followed by a zooming out to processing the entire face, followed by a zooming back in to diagnostic features (e.g. the opened eyes in “fear”, the mouth in “happy”). A model categorizer demonstrates that at 200 ms, the left and right brain have represented enough information to predict behavioral categorization performance.     

Lectin activity from embryonic chick brain,heart, and liver: Changes with development

Extracts of embryonic chick brain, heart, and liver agglutinate glutaraldehyde-fixed trypsinized or pronase-treated rabbit erythrocytes. Agglutination activity of extracts from each organ was inhibited by a number of saccharides. Lactose was the most potent saccharide inhibitor of those tested. The specific agglutination activity of the extracts from each of the organs studied changed with development of the embryo. In general, specific agglutination activity declined later in embryogenesis, and after hatching. However, the pattern of developmental change differed for each of the organs tested. Liver was unusual in that, after hatching, agglutination activity rose again; and the agglutinin found at this time was apparently different from that found in the embryo.     

Higher Urinary Bisphenol A Concentration Is Associated with Unexplained Recurrent Miscarriage Risk: Evidence from a Case-Control Study in Eastern China

BackgroundEvidence about the association between Bisphenol A (BPA) and the risk of recurrent miscarriage (RM) in human being is still limited.ObjectiveWe evaluated the association of urinary BPA concentrations with RM in human being.MethodsA hospital-based 1:2 matched case-control study on RM was carried out in Suzhou and Kunshan in Jiangsu Province in China between August 2008 and November 2011. Total urinary BPA concentrations in 264 eligible urine samples (102 RM patients and 162 controls) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon test and conditional logistic regression were used to estimate the differences between the groups and odds ratios (OR) with 95% confidence intervals (CI), respectively.ResultsThe median ± IQR (interquartile range) (P₇₅-P₂₅) values of non-creatinine-adjusted total urinary BPA levels in the RM patients and the controls were 1.66±3.69ng/ml and 0.58±1.07ng/ml, respectively (0.98±2.67μg/g Cr (creatinine) and 0.40±0.77μg/g Cr. The adjusted BPA level was significantly higher in the RM patients than in the controls (Wilcoxon test, Z = 4.476, P<0.001). Higher level of urinary BPA was significantly associated with an increased risk of RM (P-trend <0.001). Compared to the groups with urinary BPA levels less than 0.16μg/g Cr, the women with levels of 0.40–0.93μg/g Cr and 0.93μg/g Cr or above had a significantly higher risk of RM (OR = 3.91, 95%CI: 1.23–12.45 and OR = 9.34, 95%CI: 3.06–28.44) that persisted after adjusting for confounding factors. The time from recently RM date to recruitment does not significantly influence the urinary BPA level (P = 0.090).ConclusionExposure to BPA may be associated with RM risk.     

Endogenous cis,trans-Abscisic Acid and Pea Seed Development: Evidence for a Role in Seed Growth from Changes Induced by Temperature

Measurements were made using GC/MS SIM¹ of the effects of temperatureon cis,trans-ABA levels in developing ovules and embryos oftwo pea genotypes contrasted in seed size. These effects werethen related to differences in the growth of the pods, seeds,embryos, and testae. In both genotypes high temperatures hastenedthe onset and rate of logarithmic and then linear growth, greatlyshortening the duration of pod and seed development but withoutgreatly altering seed size. Cis,trans-ABA was most concentratedxin the ovules immediately after fertilization. It also accumulatedin the embryo, more rapidly in the larger-seeded line, duringseed maturation. The stage when accumulation in the embryo beganwas the same irrespective of temperature. Accumulation ceasedwhen the pods started to desiccate. The effects of differentconstant temperatures on the maximum levels of embryo cis,trans-ABAwere relatively small and confounded in one genotype by variationin ovule abortion and in the other by differences in the stagewhen cis,trans-ABA accumulation ceased. However, when plantswere transferred from 13 °C to 29 °C at two differentstages during seed maturation, further seed growth was greatlyinhibited coincident with a substantial increase in embryo cis-trans-ABA.The results suggested a role for cis,trans-ABA in the controlof cotyledon enlargement during the linear phase of seed growth.     

Cephalometric Pattern and Nasal Patency in Children with Primary Snoring: The Evidence of a Direct Correlation

Introduction

Sleep disordered breathing (SDB) might affect craniofacial growth and children with obstructive sleep apnea syndrome present an increase in total and lower anterior heights of the face and a more anterior and inferior position of the hyoid bone when compared to nasal breathers.

Objective

To investigate the correlation between rhinomanometric and cephalometric parameters in children with primary snoring (PS), without apnea or gas exchange abnormalities.

Materials and Methods

Thirty children with habitual snoring (16 females and 14 males) aged 4–8 years (mean age 6.85±1.51 years) were selected by a SDB validate questionnaire. All subjects underwent lateral cephalometric, panoramic radiographies.

Results

In our sample 10 children (33%) had snoring 3 nights/week, 11 (37%) 4–6 nights/week and 9 (30%) every night/week. Overall 7 patients (23.3%) were affected by adenoid hypertrophy (AH), 4 (13.3%) by tonsillar hypertrophy (TH) and 13 (43.3%) by AH and TH. We found a more vertical position of the hyoid bone to the mandibular plane (H⊥VT) in patients with a higher frequency (7.3±2.7 vs 7.6±3.7 vs 10.9±2.5 in children snoring 3 nights/week, 4–6 nights/week and every night/week respectively; p = 0.032). Concerning nasal patency significant correlations were found with ANB (maxillary and jaw position with respect to the cranial base), NS∧Ar (growth predictor), sumangle, FMA (total divergence), SnaSnp∧GoMe (inferior divergence), BaN∧PtGn (facial growth pattern), Phw1_PsP (posterosuperior airway space), AHC3H (the horizontal distance between the most anterosuperior point of the hyoid bone and the third cervical vertebra).

Conclusion

The present study supports the relationship between nasal obstruction and specific craniofacial characteristics in children with primary snoring and lead us to hypothesize that nasal obstruction might explain the indirect link between snoring and cephalometric alterations.     

When Feelings Arise with Meanings: How Emotion and Meaning of a Native Language Affect Second Language Processing in Adult Learners

To determine when and how L2 learners start to process L2 words affectively and semantically, we conducted a longitudinal study on their interaction in adult L2 learners. In four test sessions, spanning half a year of L2 learning, we monitored behavioral and ERP learning-related changes for one and the same set of words by means of a primed lexical-decision paradigm with L1 primes and L2 targets. Sensitivity rates, accuracy rates, RTs, and N400 amplitude to L2 words and pseudowords improved significantly across sessions. A semantic priming effect (e.g, prime “driver”facilitating response to target “street”) was found in accuracy rates and RTs when collapsing Sessions 1 to 4, while this effect modulated ERP amplitudes within the first 300 ms of L2 target processing. An overall affective priming effect (e.g., “sweet” facilitating”taste”) was also found in RTs and ERPs (posterior P1). Importantly, the ERPs showed an L2 valence effect across sessions (e.g., positive words were easier to process than neutral words), indicating that L2 learners were sensitive to L2 affective meaning. Semantic and affective priming interacted in the N400 time-window only in Session 4, implying that they affected meaning integration during L2 immersion together. The results suggest that L1 and L2 are initially processed semantically and affectively via relatively separate channels that are more and more linked contingent on L2 exposure.