The Impact of Patient Factors on Objective Cochlear Implant Verification Using Acoustic Cortical Auditory-Evoked Potentials.

INTRODUCTION: Hearing loss is a major global public health issue that negatively impacts quality of life, communication, cognition, social participation, and mental health. The cochlear implant (CI) is the most efficacious treatment for severe-to-profound sensorineural hearing loss. However, variability in outcomes remains high among CI users. Our previous research demonstrated that the existing subjective methodology of CI programming does not consistently produce optimal stimulation for speech perception, thereby limiting the potential for CI users to derive the maximum device benefit to achieve their peak potential. We demonstrated the benefit of utilising the objective method of measuring auditory-evoked cortical responses to speech stimuli as a reliable tool to guide and verify CI programming and, in turn, significantly improve speech perception performance. The present study was designed to investigate the impact of patient- and device-specific factors on the application of acoustically-evoked cortical auditory-evoked potential (aCAEP) measures as an objective clinical tool to verify CI mapping in adult CI users with bilateral deafness (BD). METHODS: aCAEP responses were elicited using binaural peripheral auditory stimulation for four speech tokens (/m/, /g/, /t/, and /s/) and recorded by HEARLab™ software in adult BD CI users. Participants were classified into groups according to subjective or objective CI mapping procedures to elicit present aCAEP responses to all four speech tokens. The impact of patient- and device-specific factors on the presence of aCAEP responses and speech perception was investigated between participant groups. RESULTS: Participants were categorised based on the presence or absence of the P1-N1-P2 aCAEP response to speech tokens. Out of the total cohort of adult CI users (n = 132), 63 participants demonstrated present responses pre-optimisation, 37 participants exhibited present responses post-optimisation, and the remaining 32 participants either showed an absent response for at least one speech token post-optimisation or did not accept the optimised CI map adjustments. Overall, no significant correlation was shown between patient and device-specific factors and the presence of aCAEP responses or speech perception scores. CONCLUSION: This study reinforces that aCAEP measures offer an objective, non-invasive approach to verify CI mapping, irrespective of patient or device factors. These findings further our understanding of the importance of personalised CI rehabilitation through CI mapping to minimise the degree of speech perception variation post-CI and allow all CI users to achieve maximum device benefit.

The use of patient-report measures and intervention strategies for children and adolescents with chronic tinnitus: a scoping review.

BACKGROUND: Chronic tinnitus during childhood/adolescence can be associated with impaired quality of life. Guidelines for managing paediatric tinnitus recommend assessment and interventions are often based upon the experiences and opinions of guideline committee members. OBJECTIVE: To examine patient response tools used for the assessment and management of childhood tinnitus and how interventions had been evaluated. DESIGN: A structured scoping review (i) identifying and critically appraising patient response measures (PRMs) assessing tinnitus in children/adolescents, and (ii) critically appraising evidence supporting reported interventions. Original papers written in English, involving paediatric participants ≤19 years, reporting (i) application of established PRMs to assess the experience of chronic tinnitus or (ii) application and evaluation of tinnitus interventions were included. STUDY SAMPLE: Papers written in English, identifying, or assessing the experience of chronic tinnitus (>3 months) as a primary complaint during childhood/adolescence in participants ≤19 years of age using a PRM and studies evaluating the application of non-pharmaceutical interventions for tinnitus in children/adolescents. RESULTS: Six studies involving the assessment of tinnitus during childhood/adolescence using a PRM were identified and evaluated. Three established (previously named, described, and published) PRMs were applied of which none were developed specifically for children/adolescents. Three behavioural tinnitus interventions and three combination intervention strategies (coupling of psychological intervention with sound enrichment) had been applied to and evaluated within paediatric populations. CONCLUSIONS: Although clinicians are seeing children/adolescents with tinnitus, they are evaluating and managing children's distress without appropriate PRMs, and little evidence exists to support clinical interventions.

Ear and hearing outcomes in Aboriginal infants living in an urban Australian area: the Djaalinj Waakinj birth cohort study.

OBJECTIVE: Describe the ear and hearing outcomes in Aboriginal infants in an Australian urban area. DESIGN: Aboriginal infants enrolled in the Djaalinj Waakinj prospective cohort study had ear health screenings at ages 2-4, 6-8 and 12-18 months and audiological assessment at ∼12 months of age. Sociodemographic, environmental characteristics, otoscopy, otoacoustic emissions, tympanometry and visual reinforcement audiometry data were collected. STUDY SAMPLE: 125 infants were enrolled in the study; 67 completed audiological assessment, 62, 54, and 58 of whom attended ear screenings at 2-4, 6-8 and 12-18 months. RESULTS: Of the children that attended the audiological assessment, 36.5%, 50% and 64.3% of infants had otitis media (OM) at 2-4, 6-8 and 12-18 months. Using a 10 dB correction factor, 44.8% of infants had hearing loss (HL) (≥ 25 dB HL) at ∼ 12 months of age. More males (X2=5.4 (1df, p = 0.02)) and infants with OM at audiological assessment (X2=5.8 (1df, p = 0.02)) had HL. More infants that used a pacifier at 12-18 months of age had HL (X2=4.7 (1df, p = 0.03)). CONCLUSION: Aboriginal infants in an urban area have high rates of HL and OM, which requires early surveillance and timely treatment to reduce the medical and developmental impacts of OM and HL.

Hearing aid review appointment: clients' reasons for attendance and non-attendance.

Objective: To investigate hearing aid owners' decisions to attend or not to attend an annual hearing aid review (HAR) appointment. To investigate the possible factors associated with appointment attendance, including age, gender, transportation, travel time, and hearing aid outcomes.Design: A prospective cohort study. Potential participants were notified of their annual HAR appointment in the usual process employed by their clinic. Two months later, potential participants were identified as those who had attended and those who had not attended an appointment.Study sample: One hundred and twenty adult hearing aid users ranging in age from 26 to 100 (M = 74, SD = 11) years recruited from a single hearing clinic in Perth, Western Australia.Results: Factors found to be significantly associated with attendance at an annual HAR appointment included hearing aid funding source (government subsidised), participants valuing the importance and benefit of the appointment, and superior hearing aid outcomes.Conclusions: Within a controlled practice setting, appointment attendance is influenced by some factors modifiable by the clinician, including providing better education about the process and purpose of the HAR appointment. The value of the HAR appointment was emphasised by the positive association between better hearing aid outcomes HAR appointment attendance.

Low-intensity repetitive transcranial magnetic stimulation over prefrontal cortex in an animal model alters activity in the auditory thalamus but does not affect behavioural measures of tinnitus.

Tinnitus, a phantom auditory percept, is strongly associated with cochlear trauma. The latter leads to central changes in auditory pathways such as increased spontaneous activity and this may be involved in tinnitus generation. As not all people with cochlear trauma develop tinnitus, recent studies argue that non-auditory structures, such as prefrontal cortex (PFC), play an important role in tinnitus development. As part of sensory gating circuitry, PFC may modify activity in auditory thalamus and consequently in auditory cortex. Human studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive tool for neurostimulation, can alter tinnitus perception. This study used a guinea pig model of hearing loss and tinnitus to investigate effects of low-intensity rTMS (LI-rTMS) over PFC on tinnitus and spontaneous activity in auditory thalamus. In addition, immunohistochemistry for calbindin and parvalbumin in PFC was used to investigate the possible mechanism of action of LI-rTMS. Three treatment groups were compared: sham treatment, LI, low frequency (1 Hz) or LI, high frequency (10 Hz) rTMS (10 min/day, 2 weeks, weekdays only). None of the treatments affected the behavioural measures of tinnitus but spontaneous activity was significantly increased in auditory thalamus after 1 Hz and 10 Hz treatment. Immunostaining showed significant effects of rTMS on the density of calcium-binding protein expressing neurons in the dorsal regions of the PFC suggesting that rTMS treatment evoked plasticity in cortex. In addition, calbindin-positive neuron density in the superficial region of PFC was negatively correlated with spontaneous activity in auditory thalamus suggesting a possible mechanism for change in activity observed.

Acoustic trauma increases inhibitory effects of amygdala electrical stimulation on thalamic neurons in a rat model.

Acoustic trauma (AT) induced hearing loss elicits plasticity throughout the central auditory pathway, including at the level of the medial geniculate nucleus (MGN). Hearing loss also results in altered neuronal responses in the amygdala, which is involved in sensory gating at the level of the MGN. However, whether these altered responses in the amygdala affect sensory gating at the level of the MGN requires further evaluation. The current study aimed to investigate the effects of AT-induced hearing loss on the functional connectivity between the amygdala and the MGN. Male Sprague-Dawley rats were exposed to either sham (n = 5; no sound) or AT (n = 6; 16 kHz, 1 h, 124 dB SPL) under full anaesthesia. Auditory brainstem response (ABR) recordings were made to determine hearing thresholds. Two weeks post-exposure, extracellular recordings were used to assess the effect of electrical stimulation of the amygdala on tone-evoked (sham n = 22; AT n = 30) and spontaneous (sham n = 21; AT n = 29) activity of single neurons in the MGN. AT caused a large temporary and small permanent ABR threshold shift. Electrical stimulation of the amygdala induced differential effects (excitatory, inhibitory, or no effect) on both tone-evoked and spontaneous activity. In tone-evoked activity, electrical stimulation at 300 µA, maximum current, caused a significantly larger reduction in firing rate in AT animals compared to sham, due to an increase in the magnitude of inhibitory effects. In spontaneous activity, there was also a significantly larger magnitude of inhibitory effects following AT. The findings confirm that activation of the amygdala results in changes in MGN neuronal activity, and suggest the functional connectivity between the amygdala and the MGN is significantly altered following AT and subsequent hearing loss.

A repeated measures cognitive affective bias test in rats: comparison with forced swim test.

RATIONALE: There is an urgent need to identify behaviours in animals that can provide insight into the aetiology and potential treatment of depression in humans. OBJECTIVES: This study aimed to validate a repeated measures cognitive affective bias (CAB) test in a rat model of chronic stress and compare CAB with forced swim test (FST) measures. METHODS: Male and female Sprague Dawley rats were trained to associate large and small rewards with scent, spatial, and tactile cues, and their response to an ambiguous tactile stimulus tested. Rats underwent weekly CAB testing for 4 weeks with no intervention, or for 2 weeks of chronic restraint stress (CRS), followed by 2 weeks of fluoxetine, vehicle, or no treatment. CRS rats also underwent the FST at selected timepoints. RESULTS: In control rats, CAB was positive and remained stable over the 4-week period. In CRS-fluoxetine and CRS-vehicle groups, CAB was initially positive, became negative during chronic restraint stress, and returned to positive by 2 weeks after treatment. However, in the CRS-no treatment group, CAB was variable at the outset and unstable over time. Behaviour in the FST was not affected by treatment, and there was no correlation between CAB and FST outcomes. CONCLUSIONS: Instability in the CRS-no treatment group precluded interpretation of the impact of fluoxetine on CAB post-CRS. Our results suggest that behaviour in the FST does not reflect or alter affective state and support the use of CAB tests as part of the behavioural testing repertoire for preclinical animal models of affective disorders.

Auditory Event-Related Potentials in Older Adults with Subjective Memory Complaints.

BACKGROUND: Auditory event-related potentials (AERPs) have been suggested as possible biomarkers for the early diagnosis of Alzheimer's disease (AD). However, no study has investigated AERP measures in individuals with subjective memory complaints (SMCs), who have been suggested to be at a pre-clinical stage of AD. OBJECTIVE: This study investigated whether AERPs in older adults with SMC can be used to objectively identify those at high risk of developing AD. METHODS: AERPs were measured in older adults. Presence of SMC was determined using the Memory Assessment Clinics Questionnaire (MAC-Q). Hearing thresholds using pure-tone audiometry, neuropsychological data, levels of amyloid-ß burden and Apolipoprotein E (APOE)ɛ genotype were also obtained A classic two-tone discrimination (oddball) paradigm was used to elicit AERPs (i.e., P50, N100, P200, N200, and P300). RESULTS: Sixty-two individuals (14 male, mean age 71.9±5.2 years) participated in this study, of which, 43 (11 male, mean age 72.4±5.5 years) were SMC and 19 (3 male, mean age 70.8±4.3 years) were non-SMC (controls). P50 latency was weakly but significantly correlated with MAC-Q scores. In addition, P50 latencies were significantly longer in Aß+ individuals compared to Aß- individuals. CONCLUSION: Results suggest that P50 latencies may be a useful tool to identify individuals at higher risk (i.e., participants with high Aß burden) of developing measurable cognitive decline. Further longitudinal and cross-sectional studies in a larger cohort on SMC individuals are warranted to determine if AERP measures could be of significance for the detection of pre-clinical AD.

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model.

Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (µCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using µCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by µCT, before and after contrast staining with osmium tetroxide (OsO4), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that µCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO4 significantly enhanced the visible tissue reaction detected using µCT. Overall, µCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.

Hyperactivity in the ventral cochlear nucleus after cochlear trauma.

The emergence of hyperactivity in the form of elevated spontaneous firing rates after cochlear trauma has been well documented in a number of central auditory structures, including the auditory cortex, inferior colliculus, and dorsal subdivision of the cochlear nucleus. This hyperactivity is of interest as a possible neural substrate of tinnitus. Whether the ventral subdivision of the cochlear nucleus shows hyperactivity has never been investigated despite the fact that, like the dorsal division, it also receives direct input from the damaged cochlea and supplies major ascending inputs to brainstem and midbrain auditory centers. We investigated spontaneous neuronal firing rates in the ventral cochlear nucleus in a guinea pig model of cochlear trauma in which we have shown that hyperactivity consistently develops in the inferior colliculus (Mulders and Robertson, 2009). The mean spontaneous firing rates of ventral cochlear nucleus neurons was significantly elevated compared to sham controls. This hyperactivity was more evident in primary-like and onset categories of neurons. Hyperactivity in the ventral subdivision of cochlear nucleus therefore needs to be considered in relation to neural models of the genesis of tinnitus.

Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus.

Sensory gating is the process whereby irrelevant sensory stimuli are inhibited on their way to higher cortical areas, allowing for focus on salient information. Sensory gating circuitry includes the thalamus as well as several cortical regions including the prefrontal cortex (PFC). Defective sensory gating has been implicated in a range of neurological disorders, including tinnitus, a phantom auditory perception strongly associated with cochlear trauma. Recently, we have shown in rats that functional connectivity between PFC and auditory thalamus, i.e., the medial geniculate nucleus (MGN), changes following cochlear trauma, showing an increased inhibitory effect from PFC activation on the spontaneous firing rate of MGN neurons. In this study, we further investigated this phenomenon using a guinea pig model, in order to demonstrate the validity of our finding beyond a single species and extend data to include data on sound evoked responses. Effects of PFC electrical stimulation on spontaneous and sound-evoked activity of single neurons in MGN were recorded in anaesthetised guinea pigs with normal hearing or hearing loss 2 weeks after acoustic trauma. No effect, inhibition and excitation were observed following PFC stimulation. The proportions of these effects were not different in animals with normal hearing and hearing loss but the magnitude of effect was. Indeed, hearing loss significantly increased the magnitude of inhibition for sound evoked responses, but not for spontaneous activity. The findings support previous observations that PFC can modulate MGN activity and that functional changes occur within this pathway after cochlear trauma. These data suggest hearing loss can alter sensory gating which may be a contributing factor toward tinnitus development.

Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Tinnitus in a Guinea Pig Model.

The auditory phantom sensation of tinnitus is associated with neural hyperactivity. Modulating this hyperactivity using repetitive transcranial magnetic stimulation (rTMS) has shown beneficial effects in human studies. Previously, we investigated rTMS in a tinnitus animal model and showed that rTMS over prefrontal cortex (PFC) attenuated tinnitus soon after treatment, likely via indirect effects on auditory pathways. Here, we explored the duration of these beneficial effects. Acoustic trauma was used to induce hearing loss and tinnitus in guinea pigs. Once tinnitus developed, high-frequency (20 Hz), high-intensity rTMS was applied over PFC for two weeks (weekdays only; 10 min/day). Behavioral signs of tinnitus were monitored for 6 weeks after treatment ended. Tinnitus developed in 77% of animals between 13 and 60 days post-trauma. rTMS treatment significantly reduced the signs of tinnitus at 1 week on a group level, but individual responses varied greatly at week 2 until week 6. Three (33%) of the animals showed the attenuation of tinnitus for the full 6 weeks, 45% for 1-4 weeks and 22% were non-responders. This study provides further support for the efficacy of high-frequency repetitive stimulation over the PFC as a therapeutic tool for tinnitus, but also highlights individual variation observed in human studies.

Comparison of Auditory Steady-State Responses With Conventional Audiometry in Older Adults.

Behavioral measures, such as pure-tone audiometry (PTA), are commonly used to determine hearing thresholds, however, PTA does not always provide reliable hearing information in difficult to test individuals. Therefore, objective measures of hearing sensitivity that require little-to-no active participation from an individual are needed to facilitate the detection and treatment of hearing loss in difficult to test people. Investigation of the reliability of the auditory steady-state response (ASSR) for measuring hearing thresholds in older adults is limited. This study aimed to investigate if ASSR can be a reliable, objective measure of frequency specific hearing thresholds in older adults. Hearing thresholds were tested at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz in 50 participants aged between 60 and 85 years old, using automated PTA and ASSR. Hearing thresholds obtained from PTA and ASSR were found to be significantly correlated (p < .001) in a cohort consisting of participants with normal hearing or mild hearing loss. ASSR thresholds were significantly higher as compared to PTA thresholds, but for the majority of cases the difference remained within the clinically acceptable range (15 dB). This study provides some evidence to suggest that ASSR can be a valuable tool for estimating objective frequency-specific hearing thresholds in older adults and indicate that ASSR could be useful in creating hearing treatment plans for older adults who are unable to complete behavioral PTA. Further research on older adults is required to improve the methodological features of ASSR to increase consistency and reliability, as well as minimize some of the limitations associated with this technique.

Understanding the Relationship Between Age-Related Hearing Loss and Alzheimer's Disease: A Narrative Review.

Evidence suggests that hearing loss (HL), even at mild levels, increases the long-term risk of cognitive decline and incident dementia. Hearing loss is one of the modifiable risk factors for dementia, with approximately 4 million of the 50 million cases of dementia worldwide possibly attributed to untreated HL. This paper describes four possible mechanisms that have been suggested for the relationship between age-related hearing loss (ARHL) and Alzheimer's disease (AD), which is the most common form of dementia. The first mechanism suggests mitochondrial dysfunction and altered signal pathways due to aging as a possible link between ARHL and AD. The second mechanism proposes that sensory degradation in hearing impaired people could explain the relationship between ARHL and AD. The occupation of cognitive resource (third) mechanism indicates that the association between ARHL and AD is a result of increased cognitive processing that is required to compensate for the degraded sensory input. The fourth mechanism is an expansion of the third mechanism, i.e., the function and structure interaction involves both cognitive resource occupation (neural activity) and AD pathology as the link between ARHL and AD. Exploring the specific mechanisms that provide the link between ARHL and AD has the potential to lead to innovative ideas for the diagnosis, prevention, and/or treatment of AD. This paper also provides insight into the current evidence for the use of hearing treatments as a possible treatment/prevention for AD, and if auditory assessments could provide an avenue for early detection of cognitive impairment associated with AD.

The actions of dopamine receptors in the guinea pig cochlea.

Dopamine, a major lateral olivocochlear efferent neurotransmitter, exerts both excitatory and inhibitory effects on the central nervous system depending on the receptor involved. We investigated the effects of different dopamine receptors on the cochlea by perilymphatic perfusion with D(1/5), D(2) and D(3) receptor agonists and antagonists and recording neural and hair cell responses (compound action potential - CAP; summating potential - SP) before, during and after perfusions. The D(1/5) agonist resulted in marked suppression of CAP amplitudes whilst leaving SP amplitudes unchanged, suggesting an inhibitory action of these receptors on afferent dendrites. The D(1/5) antagonist had little or no effect, suggesting that there is no influence of tonic dopamine release on these receptors. In contrast, perfusing a D(2) receptor antagonist resulted in marked suppression of CAP suggesting an excitatory action of the receptors and a strong influence of tonic dopamine release on the D(2) receptors. The D(2) agonist had little effect, implying that tonic dopamine release is maximally activating this class of dopamine receptors. D(2) antagonists resulted in reduction of SP, cochlear microphonic and distortion product otoacoustic emission amplitudes, suggesting that D(2) receptor action is not confined to afferent dendrites. Perfusion with D(3) agonists and antagonists had no effect.

Changes in Prefrontal Cortex-Thalamic Circuitry after Acoustic Trauma.

In the adult auditory system, loss of input resulting from peripheral deafferentation is well known to lead to plasticity in the central nervous system, manifested as reorganization of cortical maps and altered activity throughout the central auditory pathways. The auditory system also has strong afferent and efferent connections with cortico-limbic circuitry including the prefrontal cortex and the question arises whether this circuitry is also affected by loss of peripheral input. Recent studies in our laboratory showed that PFC activation can modulate activity of the auditory thalamus or medial geniculate nucleus (MGN) in normal hearing rats. In addition, we have shown in rats that cochlear trauma resulted in altered spontaneous burst firing in MGN. However, whether the PFC influence on MGN is changed after cochlear trauma is unknown. We investigated the effects of electrical stimulation of PFC on single neuron activity in the MGN in anaesthetized Wistar rats 2 weeks after acoustic trauma or sham surgery. Electrical stimulation of PFC showed a variety of effects in MGN neurons both in sham and acoustic trauma groups but inhibitory responses were significantly larger in the acoustic trauma animals. These results suggest an alteration in functional connectivity between PFC and MGN after cochlear trauma. This change may be a compensatory mechanism increasing sensory gating after the development of altered spontaneous activity in MGN, to prevent altered activity reaching the cortex and conscious perception.

Reflections on How Tinnitus Impacts the Lives of Children and Adolescents.

Objectives The aim of this study was to generate a conceptual framework describing which aspects of children and adolescents' lives are affected by chronic tinnitus. Design Views and experiences of 32 participants from two participant groups informed this study: (a) a tinnitus group, consisting of adults who had experienced tinnitus during childhood and/or adolescence and primary carers of children/adolescents with tinnitus, and (b) a clinicians' group, consisting of clinicians who provided care for children/adolescents with tinnitus. Participants produced statements describing aspects of children/adolescents' lives that may be affected by chronic tinnitus. Key concepts were identified through the processes of sorting the statements and rating them for degree of associated impact. Result Participants identified 118 unique aspects of the lives of children/adolescents who may be affected by chronic tinnitus. These were clustered into four concepts: (a) emotional well-being, (b) academic performances, (c) social/relationa, and (d) auditory/cognitive processing. At a group level, participants rated the impact of tinnitus as above a slight degree but below a moderate degree of impact. However, individual participant's ratings indicated a range of perceived impact for each statement. Conclusions The experience of chronic tinnitus during childhood and adolescence extends beyond the mere perception of sound. The perception of tinnitus may impact a child's emotional well-being, academic performances, social/relational, and auditory/cognitive processing. The impact of tinnitus in one aspect of a child's life may influence other aspects of their life. While at a group level, participants regarded the impact of tinnitus as "somewhat more than mild" to "less than moderate"; individual participant's ratings indicate that the impact from chronic tinnitus may be highly individual and highlighted the importance of individual assessment and management. Clinically, tinnitus management during childhood and adolescence may be improved if clinicians consider the impact and manifestation of tinnitus within each child's daily life and tailor tinnitus education and management strategies accordingly.

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus.

Tinnitus, a phantom auditory perception that can seriously affect quality of life, is generally triggered by cochlear trauma and associated with aberrant activity throughout the auditory pathways, often referred to as hyperactivity. Studies suggest that non-auditory structures, such as prefrontal cortex (PFC), may be involved in tinnitus generation, by affecting sensory gating in auditory thalamus, allowing hyperactivity to reach the cortex and lead to perception. Indeed, human studies have shown that repetitive transcranial magnetic stimulation (rTMS) of PFC can alleviate tinnitus. The current study investigated whether this therapeutic effect is achieved through inhibition of thalamic hyperactivity, comparing effects of two common clinical rTMS protocols with sham treatment, in a guinea pig tinnitus model. Animals underwent acoustic trauma and once tinnitus developed were treated with either intermittent theta burst stimulation (iTBS), 20 Hz rTMS, or sham rTMS (10 days, 10 min/day; weekdays only). Tinnitus was reassessed and extracellular recordings of spontaneous tonic and burst firing rates in auditory thalamus made. To verify effects in PFC, densities of neurons positive for calcium-binding proteins, calbindin and parvalbumin, were investigated using immunohistochemistry. Both rTMS protocols significantly reduced tinnitus compared to sham. However, spontaneous tonic firing decreased following 20 Hz stimulation and increased following iTBS in auditory thalamus. Burst rate was significantly different between 20 Hz and iTBS stimulation, and burst duration was increased only after 20 Hz treatment. Density of calbindin, but not parvalbumin positive neurons, was significantly increased in the most dorsal region of PFC indicating that rTMS directly affected PFC. Our results support the involvement of PFC in tinnitus modulation, and the therapeutic benefit of rTMS on PFC in treating tinnitus, but indicate this is not achieved solely by suppression of thalamic hyperactivity.

Reducing the Impact of Tinnitus on Children and Adolescents' Lives: A Mixed-Methods Concept Mapping Study.

OBJECTIVES: To generate a conceptual framework describing what is done to reduce the impact of chronic tinnitus on the lives of children and adolescents. DESIGN: Views and experiences of 32 adults from two participant groups informed this concept mapping study: (i) a tinnitus group (adults who experienced tinnitus during childhood/adolescence, and primary carers of children/adolescents with tinnitus) and (ii) a clinicians' group (clinicians who provided care for children/adolescents with tinnitus). Participants produced statements describing what is done to reduce the impact of chronic tinnitus on the lives of children and adolescents who experience it. Through grouping and rating processes, they identified key concepts and inferred their associated benefit. RESULTS: The participants generated 102 unique statements across four concepts: (1) Education, Support, and Counselling; (2) Support from Parents and Teachers; (3) Clinical Assessments and Management; and (4) Self-Management Techniques. Many statements highlighted the need for child-friendly and patient-centred care. Adults with personal experience of childhood tinnitus tended to perceive many of the statements as more beneficial than did the clinician group. CONCLUSIONS: Although many children will develop management strategies to assist them with their tinnitus, both the adults who experienced tinnitus as children and their parents valued strategies involving clinical care, knowledge, and expertise. Participants from the tinnitus group perceived a greater degree of benefit associated with strategies from all four clusters than the clinicians' group. However, both groups perceived the greatest degree of benefit as being associated with activities and strategies within the Education, Support, and Counselling and the Clinical Assessments and Management clusters. Both groups identified that recognising the occurrence of tinnitus for children and adolescents, acknowledging the potential for associated distress, and initiating clinical care provide the nexus of effective management. Addressing the concerns and needs of parents was also perceived as valuable; hence, approaching the management of tinnitus during childhood and adolescence from a family-centred care framework is recommended.

Investigating Auditory Electrophysiological Measures of Participants with Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Event-Related Potential Studies.

BACKGROUND: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer's disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD. OBJECTIVE: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i.e., mild cognitive impairment (MCI) and subjective cognitive decline. METHODS: The search was performed on six major electronic databases (Ovid MEDLINE, OVID EMBASE, PsycINFO, PubMed, Scopus, and CINAHL Plus). Articles identified prior to 7 May 2019 were considered for this review. A random effects meta-analysis and analysis of between study heterogeneity was conducted using the Comprehensive Meta-Analysis software. RESULTS: The search identified 1,076 articles; 74 articles met the full inclusion criteria and were included in the systematic review, and 47 articles were included into the analyses. Pooled analysis suggests that AD participants can be differentiated from controls due to significant delays in ABR, N100, P200, N200, and P300 latencies. P300 amplitude was significantly smaller in AD participants compared to controls. P300 latencies differed significantly between MCI participants and controls based on the pooled analysis. CONCLUSION: The findings of this review indicate that some AERPs may be valuable biomarkers of AD. In conjunction with currently available clinical and neuropsychological assessments, AERPs can aid in screening and diagnosis of prodromal AD.