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1.
Brain Lang ; 252: 105413, 2024 May.
Article in English | MEDLINE | ID: mdl-38608511

ABSTRACT

Sign languages (SLs) are expressed through different bodily actions, ranging from re-enactment of physical events (constructed action, CA) to sequences of lexical signs with internal structure (plain telling, PT). Despite the prevalence of CA in signed interactions and its significance for SL comprehension, its neural dynamics remain unexplored. We examined the processing of different types of CA (subtle, reduced, and overt) and PT in 35 adult deaf or hearing native signers. The electroencephalographic-based processing of signed sentences with incongruent targets was recorded. Attenuated N300 and early N400 were observed for CA in deaf but not in hearing signers. No differences were found between sentences with CA types in all signers, suggesting a continuum from PT to overt CA. Deaf signers focused more on body movements; hearing signers on faces. We conclude that CA is processed less effortlessly than PT, arguably because of its strong focus on bodily actions.


Subject(s)
Comprehension , Deafness , Electroencephalography , Sign Language , Humans , Comprehension/physiology , Adult , Male , Female , Deafness/physiopathology , Young Adult , Brain/physiology , Evoked Potentials/physiology
2.
Hear Res ; 446: 109007, 2024 May.
Article in English | MEDLINE | ID: mdl-38608331

ABSTRACT

Despite the proven effectiveness of cochlear implant (CI) in the hearing restoration of deaf or hard-of-hearing (DHH) children, to date, extreme variability in verbal working memory (VWM) abilities is observed in both unilateral and bilateral CI user children (CIs). Although clinical experience has long observed deficits in this fundamental executive function in CIs, the cause to date is still unknown. Here, we have set out to investigate differences in brain functioning regarding the impact of monaural and binaural listening in CIs compared with normal hearing (NH) peers during a three-level difficulty n-back task undertaken in two sensory modalities (auditory and visual). The objective of this pioneering study was to identify electroencephalographic (EEG) marker pattern differences in visual and auditory VWM performances in CIs compared to NH peers and possible differences between unilateral cochlear implant (UCI) and bilateral cochlear implant (BCI) users. The main results revealed differences in theta and gamma EEG bands. Compared with hearing controls and BCIs, UCIs showed hypoactivation of theta in the frontal area during the most complex condition of the auditory task and a correlation of the same activation with VWM performance. Hypoactivation in theta was also observed, again for UCIs, in the left hemisphere when compared to BCIs and in the gamma band in UCIs compared to both BCIs and NHs. For the latter two, a correlation was found between left hemispheric gamma oscillation and performance in the audio task. These findings, discussed in the light of recent research, suggest that unilateral CI is deficient in supporting auditory VWM in DHH. At the same time, bilateral CI would allow the DHH child to approach the VWM benchmark for NH children. The present study suggests the possible effectiveness of EEG in supporting, through a targeted approach, the diagnosis and rehabilitation of VWM in DHH children.


Subject(s)
Acoustic Stimulation , Auditory Perception , Cochlear Implantation , Cochlear Implants , Electroencephalography , Memory, Short-Term , Persons With Hearing Impairments , Visual Perception , Humans , Child , Female , Cochlear Implantation/instrumentation , Male , Persons With Hearing Impairments/rehabilitation , Persons With Hearing Impairments/psychology , Case-Control Studies , Theta Rhythm , Photic Stimulation , Gamma Rhythm , Adolescent , Speech Perception , Correction of Hearing Impairment/instrumentation , Cerebral Cortex/physiopathology , Cerebral Cortex/physiology , Deafness/physiopathology , Deafness/rehabilitation , Deafness/surgery , Hearing
3.
Acta Otolaryngol ; 144(2): 130-135, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38634540

ABSTRACT

BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.


Subject(s)
Cochlear Nerve , Deafness , Evoked Potentials, Auditory, Brain Stem , Humans , Evoked Potentials, Auditory, Brain Stem/physiology , Male , Female , Child, Preschool , Cochlear Nerve/physiopathology , Cochlear Nerve/abnormalities , Deafness/physiopathology , Deafness/congenital , Deafness/surgery , Child , Constriction, Pathologic , Cochlear Implantation/methods
4.
Eur J Neurosci ; 59(10): 2596-2615, 2024 May.
Article in English | MEDLINE | ID: mdl-38441248

ABSTRACT

Auditory deprivation following congenital/pre-lingual deafness (C/PD) can drastically affect brain development and its functional organisation. This systematic review intends to extend current knowledge of the impact of C/PD and deafness duration on brain resting-state networks (RSNs), review changes in RSNs and spoken language outcomes post-cochlear implant (CI) and draw conclusions for future research. The systematic literature search followed the PRISMA guideline. Two independent reviewers searched four electronic databases using combined keywords: 'auditory deprivation', 'congenital/prelingual deafness', 'resting-state functional connectivity' (RSFC), 'resting-state fMRI' and 'cochlear implant'. Seventeen studies (16 cross-sectional and one longitudinal) met the inclusion criteria. Using the Crowe Critical Appraisal Tool, the publications' quality was rated between 65.0% and 92.5% (mean: 84.10%), ≥80% in 13 out of 17 studies. A few studies were deficient in sampling and/or ethical considerations. According to the findings, early auditory deprivation results in enhanced RSFC between the auditory network and brain networks involved in non-verbal communication, and high levels of spontaneous neural activity in the auditory cortex before CI are evidence of occupied auditory cortical areas with other sensory modalities (cross-modal plasticity) and sub-optimal CI outcomes. Overall, current evidence supports the idea that moreover intramodal and cross-modal plasticity, the entire brain adaptation following auditory deprivation contributes to spoken language development and compensatory behaviours.


Subject(s)
Cochlear Implantation , Deafness , Humans , Deafness/physiopathology , Cochlear Implantation/methods , Brain/physiopathology , Brain/diagnostic imaging , Brain/physiology , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Magnetic Resonance Imaging , Auditory Cortex/physiopathology , Auditory Cortex/diagnostic imaging , Cochlear Implants , Treatment Outcome
5.
JAMA Otolaryngol Head Neck Surg ; 149(7): 571-578, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37166823

ABSTRACT

Importance: Hearing loss is the most important modifiable risk factor for cognitive impairment; however, the association of hearing loss with anatomical and functional connectivity is not fully understood. This association may be elucidated by evaluating the findings of newer imaging technologies. Objectives: To evaluate the association of hearing loss with anatomical and functional connectivity in patients with mild cognitive impairment (MCI) by using multimodal imaging technology. Design, Setting, and Participants: This was a prospective cross-sectional study of patients with MCI under the care of a neurology clinic at the Soonchunhyang University Bucheon Hospital (Republic of Korea) from April to September 2021. Data were analyzed from April 1 to June 30, 2022. Main Outcomes and Measures: Pure tone averages (PTA) and word recognition scores were used to measure hearing acuity. Magnetic resonance imaging (MRI) and positron emission tomography scans of the brain were used to assess functional and anatomical connectivity. Results of diffusion MRI, voxel- and surface-based morphometric imaging, and global brain amyloid standardized uptake ratio were analyzed. Neuroimaging parameters of patients with MCI plus hearing loss were compared with those of patients with MCI and no hearing loss. Correlation analyses among neuroimaging parameters, PTA, and word recognition scores were performed. Results: Of 48 patients with MCI, 30 (62.5%) had hearing loss (PTA >25 dB) and 18 (37.5%) did not (PTA ≤25 dB). Median (IQR) age was 73.5 (69.0-78.0) years in the group with hearing loss and 75.0 (65.0-78.0) years in the group with normal hearing; there were 20 (66.7%) and 14 (77.8%) women in each group, respectively. The group with MCI plus hearing loss demonstrated decreased functional connectivity between the bilateral insular and anterior divisions of the cingulate cortex, and decreased fractional anisotropy in the bilateral fornix, corpus callosum forceps major and tapetum, left parahippocampal cingulum, and left superior thalamic radiation. Fractional anisotropy in the corpus callosum forceps major and bilateral parahippocampal cingulum negatively correlated with the severity of hearing loss shown by PTA testing. The 2 groups were not significantly different in global ß-amyloid uptake, gray matter volume, and cortical thickness. Conclusion and Relevance: The findings of this prospective cross-sectional study suggest that alterations in the salience network may contribute to the neural basis of cognitive impairment associated with hearing loss in patients who are on the Alzheimer disease continuum.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Deafness , Hearing Loss , Humans , Female , Aged , Male , Cross-Sectional Studies , Prospective Studies , Neuropsychological Tests , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Alzheimer Disease/diagnosis , Hearing Loss/physiopathology , Deafness/physiopathology
6.
Neuropsychologia ; 183: 108516, 2023 05 03.
Article in English | MEDLINE | ID: mdl-36796720

ABSTRACT

Prior research has found that iconicity facilitates sign production in picture-naming paradigms and has effects on ERP components. These findings may be explained by two separate hypotheses: (1) a task-specific hypothesis that suggests these effects occur because visual features of the iconic sign form can map onto the visual features of the pictures, and (2) a semantic feature hypothesis that suggests that the retrieval of iconic signs results in greater semantic activation due to the robust representation of sensory-motor semantic features compared to non-iconic signs. To test these two hypotheses, iconic and non-iconic American Sign Language (ASL) signs were elicited from deaf native/early signers using a picture-naming task and an English-to-ASL translation task, while electrophysiological recordings were made. Behavioral facilitation (faster response times) and reduced negativities were observed for iconic signs (both prior to and within the N400 time window), but only in the picture-naming task. No ERP or behavioral differences were found between iconic and non-iconic signs in the translation task. This pattern of results supports the task-specific hypothesis and provides evidence that iconicity only facilitates sign production when the eliciting stimulus and the form of the sign can visually overlap (a picture-sign alignment effect).


Subject(s)
Electrophysiology , Evoked Potentials , Models, Neurological , Sign Language , Translations , United States , Reaction Time , Photic Stimulation , Semantics , Humans , Deafness/physiopathology , Male , Female , Adult , Analysis of Variance
7.
Somatosens Mot Res ; 40(2): 47-55, 2023 06.
Article in English | MEDLINE | ID: mdl-36645806

ABSTRACT

PURPOSE: Children with hearing impairment are unable to speak and may suffer from some physical problems such as weakness in postural performance ability and development. The aim of the current study was to explore the effects of proprioception versus core stability training for an 8-week period followed by a 6-month detraining protocol on the balance performance of deaf students. MATERIALS AND METHODS: This is a randomized controlled trial design of three groups in blinded evaluators. The study was conducted at the school gym. A total of 30 participants, of male deaf students, were randomized into three groups: (1) one group receiving proprioception training (PT, n = 10), (2), one group receiving core stability training (CST, n = 10) for 8 weeks, and (3), and control group (CON, n = 10). The Balance Error Scoring System (BESS) test and Y-balance test assess static and dynamic balance at pre- and post-training following a 6-month detraining. RESULTS: Post 8 weeks of training intervention, PT and CST values showed significant improvements in both static (p = 0.001) and dynamic (p = 0.001) balance. Following the 6-month detraining, only the PT group maintained their improvements in both the static and dynamic balance tests (p = 0.348) and the CST group showed decreases in the balance tests (p = 0.034). CONCLUSIONS: The results indicate that 8 weeks rehabilitation program (PT and CST) is an optimum training modality to enhance balance in deaf students and PT induces more training effects than CST for maintaining training benefits following the detraining. Clinical trial registry number: IRCT20170312033029N2; URL: https://en.irct.ir/trial/25584; Trial Id: 25584; Registration date: 2017-12-08; Study start date; 2017-12-22.


Subject(s)
Core Stability , Deafness , Exercise Therapy , Postural Balance , Proprioception , Child , Humans , Male , Core Stability/physiology , Deafness/physiopathology , Exercise Therapy/methods , Postural Balance/physiology , Proprioception/physiology , Students , Time Factors , Treatment Outcome
8.
Nature ; 613(7943): 317-323, 2023 01.
Article in English | MEDLINE | ID: mdl-36544024

ABSTRACT

Cochlear implants (CIs) are neuroprosthetic devices that can provide hearing to deaf people1. Despite the benefits offered by CIs, the time taken for hearing to be restored and perceptual accuracy after long-term CI use remain highly variable2,3. CI use is believed to require neuroplasticity in the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to the variability in outcomes4-7. Despite extensive studies on how CIs activate the auditory system4,8-12, the understanding of CI-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator noradrenaline from the brainstem locus coeruleus (LC). Here we examine behavioural responses and neural activity in LC and auditory cortex of deafened rats fitted with multi-channel CIs. The rats were trained on a reward-based auditory task, and showed considerable individual differences of learning rates and maximum performance. LC photometry predicted when CI subjects began responding to sounds and longer-term perceptual accuracy. Optogenetic LC stimulation produced faster learning and higher long-term accuracy. Auditory cortical responses to CI stimulation reflected behavioural performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically relevant target for optimizing neuroprosthetic device use.


Subject(s)
Cochlear Implants , Deafness , Locus Coeruleus , Animals , Rats , Cochlear Implantation , Deafness/physiopathology , Deafness/therapy , Hearing/physiology , Learning/physiology , Locus Coeruleus/cytology , Locus Coeruleus/physiology , Neuronal Plasticity , Norepinephrine/metabolism , Auditory Cortex/cytology , Auditory Cortex/physiology , Auditory Cortex/physiopathology , Neurons/physiology , Reward , Optogenetics , Photometry
9.
PLoS One ; 17(2): e0262098, 2022.
Article in English | MEDLINE | ID: mdl-35213558

ABSTRACT

Longstanding cross-linguistic work on event representations in spoken languages have argued for a robust mapping between an event's underlying representation and its syntactic encoding, such that-for example-the agent of an event is most frequently mapped to subject position. In the same vein, sign languages have long been claimed to construct signs that visually represent their meaning, i.e., signs that are iconic. Experimental research on linguistic parameters such as plurality and aspect has recently shown some of them to be visually universal in sign, i.e. recognized by non-signers as well as signers, and have identified specific visual cues that achieve this mapping. However, little is known about what makes action representations in sign language iconic, or whether and how the mapping of underlying event representations to syntactic encoding is visually apparent in the form of a verb sign. To this end, we asked what visual cues non-signers may use in evaluating transitivity (i.e., the number of entities involved in an action). To do this, we correlated non-signer judgments about transitivity of verb signs from American Sign Language (ASL) with phonological characteristics of these signs. We found that non-signers did not accurately guess the transitivity of the signs, but that non-signer transitivity judgments can nevertheless be predicted from the signs' visual characteristics. Further, non-signers cue in on just those features that code event representations across sign languages, despite interpreting them differently. This suggests the existence of visual biases that underlie detection of linguistic categories, such as transitivity, which may uncouple from underlying conceptual representations over time in mature sign languages due to lexicalization processes.


Subject(s)
Deafness/prevention & control , Linguistics/trends , Sign Language , Vision, Ocular/physiology , Deafness/physiopathology , Female , Fingers/physiology , Hand/physiology , Humans , Judgment , Male , Thumb/physiology
10.
PLoS One ; 17(2): e0263516, 2022.
Article in English | MEDLINE | ID: mdl-35134072

ABSTRACT

The ability to determine a sound's location is critical in everyday life. However, sound source localization is severely compromised for patients with hearing loss who receive bilateral cochlear implants (BiCIs). Several patient factors relate to poorer performance in listeners with BiCIs, associated with auditory deprivation, experience, and age. Critically, characteristic errors are made by patients with BiCIs (e.g., medial responses at lateral target locations), and the relationship between patient factors and the type of errors made by patients has seldom been investigated across individuals. In the present study, several different types of analysis were used to understand localization errors and their relationship with patient-dependent factors (selected based on their robustness of prediction). Binaural hearing experience is required for developing accurate localization skills, auditory deprivation is associated with degradation of the auditory periphery, and aging leads to poorer temporal resolution. Therefore, it was hypothesized that earlier onsets of deafness would be associated with poorer localization acuity and longer periods without BiCI stimulation or older age would lead to greater amounts of variability in localization responses. A novel machine learning approach was introduced to characterize the types of errors made by listeners with BiCIs, making them simple to interpret and generalizable to everyday experience. Sound localization performance was measured in 48 listeners with BiCIs using pink noise trains presented in free-field. Our results suggest that older age at testing and earlier onset of deafness are associated with greater average error, particularly for sound sources near the center of the head, consistent with previous research. The machine learning analysis revealed that variability of localization responses tended to be greater for individuals with earlier compared to later onsets of deafness. These results suggest that early bilateral hearing is essential for best sound source localization outcomes in listeners with BiCIs.


Subject(s)
Hearing Loss, Bilateral/physiopathology , Sound Localization/physiology , Acoustic Stimulation/methods , Adult , Age Factors , Age of Onset , Aged , Aged, 80 and over , Auditory Perception/physiology , Cochlear Implantation/methods , Cochlear Implants/adverse effects , Cues , Deafness/physiopathology , Female , Hearing/physiology , Hearing Loss/physiopathology , Hearing Tests , Humans , Male , Middle Aged , Sound
11.
J Child Lang ; 49(2): 366-381, 2022 03.
Article in English | MEDLINE | ID: mdl-33880987

ABSTRACT

Grammatical morphology often links small acoustic forms to abstract semantic domains. Deaf and hard-of-hearing (DHH) children have reduced access to the acoustic signal and frequently have delayed acquisition of grammatical morphology (e.g., Tomblin, Harrison, Ambrose, Walker, Oleson & Moeller, 2015). This study investigated the naturalistic use of aspectual morphology in DHH children to determine if they organize this semantic domain as normal hearing (NH) children have been found to do. Thirty DHH children (M = 6;8) and 29 NH children (M = 5;11) acquiring English participated in a free-play session and their tokens of perfective (simple past) and imperfective (-ing) morphology were coded for the lexical aspect of the predicate they marked. Both groups showed established prototype effects, favoring perfective + telic and imperfective + atelic pairings over perfective + atelic and perfective + atelic ones. Thus, despite reduced access to the acoustic signal, this DHH group was unimpaired for aspectual organization.


Subject(s)
Deafness , Language Development , Persons With Hearing Impairments , Child , Deafness/physiopathology , Humans , Semantics
12.
Brain Res ; 1776: 147744, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34848173

ABSTRACT

When a brief flash is quickly presented aligned with a moving target, the flash typically appears to lag behind the moving stimulus. This effect is widely known in the literature as a flash-lag illusion (FLI). The flash-lag is an example of a motion-induced position shift. Since auditory deprivation leads to both enhanced visual skills and impaired temporal abilities, both crucial for the perception of the flash-lag effect, here we hypothesized that lack of audition could influence the FLI. 13 early deaf and 18 hearing individuals were tested in a visual FLI paradigm to investigate this hypothesis. As expected, results demonstrated a reduction of the flash-lag effect following early deafness, both in the central and peripheral visual fields. Moreover, only for deaf individuals, there is a positive correlation between the flash-lag effect in the peripheral and central visual field, suggesting that the mechanisms underlying the effect in the center of the visual field expand to the periphery following deafness. Overall, these findings reveal that lack of audition early in life profoundly impacts early visual processing underlying the flash-lag effect.


Subject(s)
Deafness/physiopathology , Illusions/physiology , Visual Perception/physiology , Adult , Female , Humans , Male , Middle Aged , Reaction Time/physiology , Visual Fields/physiology , Young Adult
13.
Genes (Basel) ; 12(10)2021 10 15.
Article in English | MEDLINE | ID: mdl-34681017

ABSTRACT

Variants in MYH14 are reported to cause autosomal dominant nonsyndromic hereditary hearing loss (ADNSHL), with 34 variants reported to cause hearing loss in various ethnic groups. However, the available information on prevalence, as well as with regard to clinical features, remains fragmentary. In this study, genetic screening for MYH14 variants was carried out using a large series of Japanese hearing-loss patients to reveal more detailed information. Massively parallel DNA sequencing of 68 target candidate genes was applied in 8074 unrelated Japanese hearing-loss patients (including 1336 with ADNSHL) to identify genomic variations responsible for hearing loss. We identified 11 families with 10 variants. The prevalence was found to be 0.14% (11/8074) among all hearing-loss patients and 0.82% (11/1336) among ADNSHL patients. Nine of the eleven variants identified were novel. The patients typically showed late-onset hearing loss arising later than 20 years of age (64.3%, 9/14) along with progressive (92.3%, 12/13), moderate (62.5%, 10/16), and flat-type hearing loss (68.8%, 11/16). We also confirmed progressive hearing loss in serial audiograms. The clinical information revealed by the present study will contribute to further diagnosis and management of MYH14-associated hearing loss.


Subject(s)
Deafness/genetics , Genetic Predisposition to Disease , Myosin Heavy Chains/genetics , Myosin Type II/genetics , Adolescent , Adult , Amino Acid Sequence/genetics , Asian People , Deafness/physiopathology , Female , Humans , Male , Middle Aged , Mutation/genetics , Pedigree , Sequence Analysis, DNA
14.
Genes (Basel) ; 12(10)2021 10 19.
Article in English | MEDLINE | ID: mdl-34681037

ABSTRACT

Mitochondrial stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). They should be suspected in anyone with an acute/subacute onset of focal neurological symptoms at any age and are usually driven by seizures. Suggestive features of an underlying mitochondrial pathology include evolving MRI lesions, often originating within the posterior brain regions, the presence of multisystemic involvement, including diabetes, deafness, or cardiomyopathy, and a positive family history. The diagnosis of MELAS has important implications for those affected and their relatives, given it enables early initiation of appropriate treatment and genetic counselling. However, the diagnosis is frequently challenging, particularly during the acute phase of an event. We describe four cases of mitochondrial strokes to highlight the considerable overlap that exists with other neurological disorders, including viral and autoimmune encephalitis, ischemic stroke, and central nervous system (CNS) vasculitis, and discuss the clinical, laboratory, and imaging features that can help distinguish MELAS from these differential diagnoses.


Subject(s)
Diagnosis, Differential , MELAS Syndrome/diagnosis , Mitochondrial Encephalomyopathies/diagnosis , Vasculitis, Central Nervous System/diagnosis , Adult , Brain/diagnostic imaging , Brain/physiopathology , Cardiomyopathies/diagnosis , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Central Nervous System/diagnostic imaging , Central Nervous System/pathology , Deafness/diagnosis , Deafness/physiopathology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/physiopathology , Female , Humans , MELAS Syndrome/diagnostic imaging , MELAS Syndrome/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Mitochondrial Encephalomyopathies/diagnostic imaging , Mitochondrial Encephalomyopathies/physiopathology , Vasculitis, Central Nervous System/diagnostic imaging , Vasculitis, Central Nervous System/physiopathology
15.
Biosci Rep ; 41(10)2021 10 29.
Article in English | MEDLINE | ID: mdl-34714320

ABSTRACT

Hearing loss (HL) is a significant public health problem and causes the most frequent congenital disability in developed societies. The genetic analysis of non-syndromic hearing loss (NSHL) may be considered as a complement to the existent plethora of diagnostic modalities available. The present study focuses on exploring more target genes with respective non-synonymous single nucleotide polymorphisms (nsSNPs) involved in the development of NSHL. The functional network analysis and variant study have successfully been carried out from the gene pool retrieved from reported research articles of the last decade. The analyses have been done through STRING. According to predicted biological processes, various variant analysis tools have successfully classified the NSHL causative genes and identified the deleterious nsSNPs, respectively. Among the predicted pathogenic nsSNPs with rsIDs rs80356586 (I515T), rs80356596 (L1011P), rs80356606 (P1987R) in OTOF have been reported in NSHL earlier. The rs121909642 (P722S), rs267606805 (P722H) in FGFR1, rs121918506 (E565A) and rs121918509 (A628T, A629T) in FGFR2 have not been reported in NSHL yet, which should be clinically experimented in NSHL. This also indicates this variant's novelty as its association in NSHL. The findings and the analyzed data have delivered some vibrant genetic pathogenesis of NSHL. These data might be used in the diagnostic and prognostic purposes in non-syndromic congenitally deaf children.


Subject(s)
Deafness/genetics , Hearing/genetics , Polymorphism, Single Nucleotide , Databases, Genetic , Deafness/diagnosis , Deafness/physiopathology , Gene Regulatory Networks , Genetic Markers , Genetic Predisposition to Disease , Humans , Network Meta-Analysis , Phenotype , Predictive Value of Tests , Protein Interaction Maps , Risk Assessment , Risk Factors , Signal Transduction
16.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Article in English | MEDLINE | ID: mdl-34583993

ABSTRACT

Dysregulation of ion and potential homeostasis in the scala media is the most prevalent cause of hearing loss in mammals. However, it is not well understood how the development and function of the stria vascularis regulates this fluid homeostasis in the scala media. From a mouse genetic screen, we characterize a mouse line, named 299, that displays profound hearing impairment. Histology suggests that 299 mutant mice carry a severe, congenital structural defect of the stria vascularis. The in vivo recording of 299 mice using double-barreled electrodes shows that endocochlear potential is abolished and potassium concentration is reduced to ∼20 mM in the scala media, a stark contrast to the +80 mV endocochlear potential and the 150 mM potassium concentration present in healthy control mice. Genomic analysis revealed a roughly 7-kb-long, interspersed nuclear element (LINE-1 or L1) retrotransposon insertion on chromosome 11. Strikingly, the deletion of this L1 retrotransposon insertion from chromosome 11 restored the hearing of 299 mutant mice. In summary, we characterize a mouse model that enables the study of stria vascularis development and fluid homeostasis in the scala media.


Subject(s)
Deafness/genetics , Retroelements/genetics , Stria Vascularis/physiology , Animals , Chromosomes, Mammalian/genetics , Deafness/metabolism , Deafness/physiopathology , Disease Models, Animal , Female , Hair Cells, Auditory/physiology , Hearing/genetics , Hearing Loss/genetics , Hearing Loss/physiopathology , Homeostasis/genetics , Homeostasis/physiology , Membrane Potentials/genetics , Membrane Potentials/physiology , Mice , Mice, Knockout , Potassium/metabolism , Pregnancy
17.
J Biol Chem ; 297(3): 101089, 2021 09.
Article in English | MEDLINE | ID: mdl-34416235

ABSTRACT

Familial British dementia and familial Danish dementia are neurodegenerative disorders caused by mutations in the gene integral membrane protein 2B (ITM2b) encoding BRI2, which tunes excitatory synaptic transmission at both presynaptic and postsynaptic termini. In addition, BRI2 interacts with and modulates proteolytic processing of amyloid-ß precursor protein (APP), whose mutations cause familial forms of Alzheimer's disease (AD) (familial AD). To study the pathogenic mechanisms triggered by the Danish mutation, we generated rats carrying the Danish mutation in the rat Itm2b gene (Itm2bD rats). Given the BRI2/APP interaction and the widely accepted relevance of human amyloid ß (Aß), a proteolytic product of APP, to AD, Itm2bD rats were engineered to express two humanized App alleles and produce human Aß. Here, we studied young Itm2bD rats to investigate early pathogenic changes in these diseases. We found that periadolescent Itm2bD rats not only present subtle changes in human Aß levels along with decreased spontaneous glutamate release and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated responses but also had increased short-term synaptic facilitation in the hippocampal Schaeffer-collateral pathway. These alterations in excitatory interneuronal communication can impair learning and memory processes and were akin to those observed in adult mice producing rodent Aß and carrying either the Danish or British mutations in the mouse Itm2b gene. Collectively, the data show that the pathogenic Danish mutation alters the physiological function of BRI2 at glutamatergic synapses across species and early in life. Future studies will determine whether this phenomenon represents an early pathogenic event in human dementia.


Subject(s)
Cataract/physiopathology , Cerebellar Ataxia/physiopathology , Deafness/physiopathology , Dementia/physiopathology , Membrane Proteins/genetics , Synaptic Transmission/physiology , Adaptor Proteins, Signal Transducing/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Cataract/metabolism , Cerebellar Ataxia/metabolism , Deafness/metabolism , Dementia/genetics , Dementia/metabolism , Disease Models, Animal , Excitatory Amino Acid Agents/metabolism , Female , Male , Membrane Proteins/metabolism , Memory , Presynaptic Terminals/metabolism , Rats , Receptors, Glutamate/metabolism , Synapses/metabolism
18.
Neurology ; 97(7 Suppl 1): S64-S72, 2021 08 17.
Article in English | MEDLINE | ID: mdl-34230203

ABSTRACT

OBJECTIVE: To systematically evaluate published patient-reported outcome measures for the assessment of hearing function and hearing-related quality of life (QoL) and recommend measures selected by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration (REiNS) as endpoints for clinical trials in neurofibromatosis type 2 (NF2). METHODS: The REiNS Patient-Reported Outcomes Working Group systematically evaluated published patient-reported outcome measures of (1) hearing function and (2) hearing-related QoL for individuals with hearing loss of various etiologies using previously published REiNS rating procedures. Ten measures of hearing functioning and 11 measures of hearing-related QoL were reviewed. Measures were numerically scored and compared primarily on their participant characteristics (including participant age range and availability of normative data), item content, psychometric properties, and feasibility for use in clinical trials. RESULTS: The Self-Assessment of Communication and the Self-Assessment of Communication-Adolescent were identified as most useful for adult and pediatric populations with NF2, respectively, for the measurement of both hearing function and hearing-related QoL. Measures were selected for their strengths in participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials. CONCLUSIONS: REiNS recommends the Self-Assessment of Communication adult and adolescent forms for the assessment of patient-reported hearing function and hearing-related QoL for NF2 clinical trials. Further work is needed to demonstrate the utility of these measures in evaluating pharmacologic or behavioral interventions.


Subject(s)
Deafness/physiopathology , Hearing Loss/physiopathology , Hearing/physiology , Neurofibromatosis 2/physiopathology , Adolescent , Adult , Child , Deafness/diagnosis , Humans , Male , Neurilemmoma/physiopathology , Neurofibromatoses/physiopathology , Patient Reported Outcome Measures , Skin Neoplasms/physiopathology
19.
Sci Rep ; 11(1): 5202, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33664324

ABSTRACT

Reading typically involves phonological mediation, especially for transparent orthographies with a regular letter to sound correspondence. In this study we ask whether phonological coding is a necessary part of the reading process by examining prelingually deaf individuals who are skilled readers of Spanish. We conducted two EEG experiments exploiting the pseudohomophone effect, in which nonwords that sound like words elicit phonological encoding during reading. The first, a semantic categorization task with masked priming, resulted in modulation of the N250 by pseudohomophone primes in hearing but not in deaf readers. The second, a lexical decision task, confirmed the pattern: hearing readers had increased errors and an attenuated N400 response for pseudohomophones compared to control pseudowords, whereas deaf readers did not treat pseudohomophones any differently from pseudowords, either behaviourally or in the ERP response. These results offer converging evidence that skilled deaf readers do not rely on phonological coding during visual word recognition. Furthermore, the finding demonstrates that reading can take place in the absence of phonological activation, and we speculate about the alternative mechanisms that allow these deaf individuals to read competently.


Subject(s)
Brain/physiology , Deafness/prevention & control , Phonetics , Reading , Adult , Brain/diagnostic imaging , Deafness/physiopathology , Electroencephalography/methods , Evoked Potentials , Female , Hearing/physiology , Humans , Male , Persons With Hearing Impairments , Semantics , Spain/epidemiology , Young Adult
20.
Sci Rep ; 11(1): 5994, 2021 03 16.
Article in English | MEDLINE | ID: mdl-33727628

ABSTRACT

Age-related hearing loss typically affects the hearing of high frequencies in older adults. Such hearing loss influences the processing of spoken language, including higher-level processing such as that of complex sentences. Hearing aids may alleviate some of the speech processing disadvantages associated with hearing loss. However, little is known about the relation between hearing loss, hearing aid use, and their effects on higher-level language processes. This neuroimaging (fMRI) study examined these factors by measuring the comprehension and neural processing of simple and complex spoken sentences in hard-of-hearing older adults (n = 39). Neither hearing loss severity nor hearing aid experience influenced sentence comprehension at the behavioral level. In contrast, hearing loss severity was associated with increased activity in left superior frontal areas and the left anterior insula, but only when processing specific complex sentences (i.e. object-before-subject) compared to simple sentences. Longer hearing aid experience in a sub-set of participants (n = 19) was associated with recruitment of several areas outside of the core speech processing network in the right hemisphere, including the cerebellum, the precentral gyrus, and the cingulate cortex, but only when processing complex sentences. Overall, these results indicate that brain activation for language processing is affected by hearing loss as well as subsequent hearing aid use. Crucially, they show that these effects become apparent through investigation of complex but not simple sentences.


Subject(s)
Aging , Deafness/etiology , Deafness/therapy , Hearing Aids , Aged , Brain Mapping , Data Analysis , Deafness/diagnosis , Deafness/physiopathology , Disease Management , Disease Susceptibility , Female , Hearing , Hearing Tests , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Treatment Outcome
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