Hearing loss in old age is associated with cognitive decline and with depression. Our study aimed to investigate the relationship between hearing loss, cognitive decline, and secondary depressive symptoms in a sample of younger and older cochlear implant candidates with profound to severe hearing loss.This study is part of a larger cohort study designated to provide information on baseline data before CI. Sixty-one cochlear implant candidates with hearing loss from adulthood onwards (>18 years) were enrolled in this study. All had symmetrical sensorineural hearing loss in both ears . Individuals with primary affective disorders, psychosis, below-average intelligence, poor German language skills, visual impairment, and a medical diagnosis with potential impact on cognition  were excluded. Four-frequency hearing thresholds  were collected. Using the Abbreviated Profile of Hearing Aid Benefit, we assessed subjective hearing in noise. Clinical and subclinical depressive symptoms were assessed with the Beck Depression Inventory (BDI II). Cognitive status was assessed with a neurocognitive test battery.Our findings revealed a significant negative association between subjective hearing in noise  and BDII. However, we did not observe any link between hearing thresholds, depression, and cognition. Additionally, no differences emerged between younger (25–54 years) and older subjects (55–75 years). Unexpectedly, further unplanned analyses unveiled correlations between subjective hearing in quiet environments (APHAB) and cognitive performance , cognitive performance . Duration of hearing loss and speech recognition at quiet (Freiburg Monosyllables) were not related to depression and cognitive performance.Impact of hearing loss on mood and cognition appears to be independent, suggesting a relationship with distinct aspects of hearing loss. These results underscore the importance of considering not only conventional audiometric measures like hearing thresholds but also variables related to hearing abilities during verbal communication in everyday life, both in quiet and noisy settings. The impact of hearing loss is generally underestimated. The Global Burden of Disease study  reveals Aging –18 is alRecently published studies have shed light on the significance of both peripheral hearing and central auditory components for cognitive performance. Among older adults, individuals with speech recognition scores in noise below the median exhibited poorer cognitive performance and experienced accelerated cognitive decline over an average follow-up period of 3.5 years compared to those with scores above the median . FurtherSeveral articles discuss possible mechanism linking adult hearing loss in older adults and cognitive decline , 23–30. To date, there has been a lack of research investigating the potential mediating role of depression between hearing loss and cognitive performance.In addition to hearing loss, depression itself appears to independently contribute to cognitive decline. Multiple studies have consistently demonstrated a link between depressive problems and cognitive decline –41. MoreNumerous recent retrospective , 48–57 aIt is important to note that the assessment of depression in various studies may vary, leading to potential confusion. Most authors , 53–57 eIn addition, several studies inform about associations between hearing loss, depression, and brain changes in middle-aged and older adults. Tang et al. reported that middle-aged adults with acquired sensorineural hearing loss had higher levels of depression and anxiety and lower functional connectivity between the amygdala and auditory cortex, striatum, multimodal processing areas, and fronto-parietal control areas compared with normal-hearing peers . Aoki etThere is also evidence that hearing and depression are related to each other via the neurotransmitter serotonin. Impaired serotonergic function in the auditory cortex has been found in normal-hearing adults with major depression . StudiesOur clinical experience and research by GBD 19 Hearing Loss Collaborators  and depression and cognitive performance, and that depression mediates between hearing loss and cognitive performance. However, some limitations of these studies should also be considered. Brewster et al.  and TsimThe primary objective of our study was to unravel the interrelationships between hearing ability, depressive status , cognitive status, and age groups (younger and older adults) in individuals with bilateral sensory onset hearing loss starting in adulthood. Specifically, we investigated whether the severity of depressive symptoms acts as a mediator of cognitive performance. Additionally, we examined potential variations between the younger and older groups regarding secondary depression, cognitive status, and the mediating role of depressive symptoms.There is a correlation between hearing ability  andSeverity  of secondary depressive symptoms.Cognitive performance .There is a correlation between severity of depressive symptoms and cognitive performance.The severity of secondary depressive symptoms mediates between hearing ability and cognitive performance.The following applies to a–c above: At least one connection between an auditory variable, depression and a cognitive variable can be established.The main hypothesis applies to both the younger and the older group .There are less depressive symptoms in the younger group.The cognitive performance is higher in the younger group.This study is part of a larger cohort study designated to provide information on baseline data before cochlear implantation. It was conducted at Medical University of Hannover, Germany (German Hearing Center) and ENT department of University Hospital Salzburg, Austria, from August 2019 to January 2023. The project was approved by local ethics committees of Hannover (protocol number: 8419_BO_S_2019) and Salzburg (protocol number: 415-E/22489/2-2019).We recruited cochlear implantn = 61 participants  are listed in The flow chart in The primary outcomes of this study were possible associations between (a) hearing status and severity  of secondary depressive symptoms in younger and older CI candidates, (b) depressive status and cognitive performance, and (c) hearing status and cognitive performance. The secondary outcomes were possible differences in these associations between the younger and older groups.Hearing assessments were conducted by qualified audiologists in double-walled, soundproof booths, following International Electrotechnical Commission (IEC) regulations. Audiometric tests were performed using equipment that adheres to IEC 60645 standards and is calibrated based on ISO 389 1–9 guidelines. The audiometric tests included measurement of pure tone threshold, with higher thresholds [four-frequency PTA  indicating lower hearing status].Speech recognition was tested with the German Freiburg Numbers (recognition of 10 two-digit recorded numbers) and the Freiburg Monosyllables . AlWe refrained from a speech recognition test in noise because clinical experience shows that many CI candidates fail a speech test in noise, with and without hearing aids (0% of speech stimuli are correctly recognized), which is due to their severe and profound hearing loss.As a substitute, we used the “background noise” subscale (BN) of the German version of the APHAB [Abbreviated Profile of Hearing Aid Benefit –84]. ThiAlthough we only needed the results of the BN subscale, the participants were asked to answer all 24 questions of the APHAB.The Beck’s Depression Inventory II –91, GermWe tested visual episodic memory and the executive functions working memory, attentional control, inhibition, cognitive flexibility, and phonemic and semantic verbal fluency. We did not examine verbal episodic memory because we could not find a validated test that measures only verbal memory , that is suitable for younger and older people, that is also suitable for people with severe and profound hearing loss, and that also has a German version.Non Verbal Learning Test (NVLT), a German test of visual episodic memory based on Kimura’s Recurring Figures Test, which is also available in computer form , to the previous number (n = 2), or even to a previous number (n = 3). Number of omissions and the number of errors are documented.An r et al.  and testr et al.  and the r et al. . In thisGo/NoGo Test was used, developed by Maquire et al.  was used , there was a template for communication that all investigators had to follow. In Salzburg, the tests were administered by clinical psychologists. In Hannover, the tests were administered by clinical staff who were experienced in communicating with individuals with hearing loss. Since the TAP tests may only be administered by psychologists , they were trained by psychologists and then supervised.To identify potential confounders such as comorbidities or other circumstances and to check the inclusion and exclusion criteria, all participants were examined by medical professionals before the audiological, cognitive and psychological investigations, which also included the general ENT status. Potential exclusion criteria were verified systematically with the help of a self-developed questionnaire, addressing predefined exclusion criteria as mentioned earlier. This questionnaire was filled out by each potential participant before the medical interview and subsequently controlled by medical staff during the examination.Since cochlear implantation is not a life-saving procedure, patient volumes at the Hannover and Salzburg clinics declined by more than 50 percent during the COVID-19 pandemic compared to the years before the pandemic. Therefore, the study was extended by 1 year. In Salzburg and in Hannover, the assessments were performed in well-ventilated rooms and partition walls made of Plexiglas between the tester and the participant were used. In Salzburg, the NVLT  was performed on a PC (there was no extra laptop as in Hannover). Since no separation was possible in this test situation, FFP2 masks were worn by the investigators . All participants were required to wear FFP2 masks. As soon as corona testing was available, all patients were tested for corona on admission to the ward.mediate function in the mediation package of statistics software R. 4.2.3. In order to assess, whether the correlations addressed in (i)–(iii) differed significantly between the younger and older group, linear multiple regressions were used including age group as a moderator. For cognitive functions, age-adjusted T-values were used as performance estimates. p-values were FDR-corrected for multiple comparisons. All missing dada were documented.Statistical analysis was carried out in IBM SPSS Statistics Version 27. Pearson correlations were used in order to assess (i) associations between hearing ability and cognitive functions, (ii) hearing ability and depression, and (iii) depression and cognitive functions. For mediation analyses were planned to use the p = 0.02). Participants with objectively worse hearing, i.e., higher PTA, had significantly worse subjective hearing in noise, i.e., lower APHAB scores. Hearing thresholds were furthermore significantly related to subjective hearing in reverberant surroundings , but not to subjective hearing in quiet [“Ease of communication”  and also not with subjective hearing of aversive and loud sounds ].Four-frequency hearing thresholds (PTA) in the better ear were significantly negatively related to subjective hearing ability in noise as assessed with the APHAB . Subjective hearing in noise as assessed with the Background Noise subscale (APHAB) was significantly negatively related to depressive symptoms as assessed with the BDI II  and BDI II (Beck’s Depression Inventory) results .As for possible associations between hearing and cognitive performance, neither objective hearing ability, as assessed with audiometric testing , nor subjective hearing ability in background noise (BN) were significantly related to any cognitive variables , all │r│< 0.23, all p > 0.07; clinical cases only, i.e., those that are at or above the cut-off value of 13 (n = 21), all │r│ < 0.24, all p > 0.29).Furthermore, severity of depressive symptoms was not related to any cognitive variables , than in the older group , though the difference in the associations between groups were not significant .The associations between subjective hearing in noise (BN) and severity of depressive symptoms (BDI II) were more pronounced in the younger group , and cognitive variables. Additional hearing variables included the remaining three subscales of the APHAB Ease of Communication (EC), Reverberant (RV) and Aversiveness (AV) as well as speech recognition in quiet (Freiburg Monosyllables) and duration of hearing loss .p > 0.19), while subjective hearing of aversive and loud sounds (AV) was also significantly negatively related to depressive symptoms . The duration of hearing loss and speech recognition were not significantly related to depression  compare As for additional hearing variables and depression, APHAP subjective hearing in quiet (EC), or in reverberant surroundings (RV) were not associated with depressive symptoms  was significantly positively associated with several cognitive variables , nonverbal visual memory as assessed with the NVLT , as well as the TMTB , compare FDR = 0.09), the nback  and Go/NoGo-Task . APHAB Subjective hearing of aversive sounds (AV) was significantly associated with semantic fluency  and GoNoGo time , but non-significantly to phonemic fluency , nonverbal memory , n-back performance  and TMTB performance . APHAB subjective hearing in reverberant surroundings (RE) was not significantly related to any cognitive variables . Although some correlations appear numerically larger in the older group, associations did not differ significantly between the older and the younger group . None of the cognitive variables were related to speech test results in quiet .As for additional hearing variables and cognitive variables, The present study was designed to assess depressive symptoms as a potential mediator of cognitive impairing effects of hearing loss. In otherwise healthy adults with bilateral hearing loss, all of whom were candidates for cochlear implantation, we found no evidence of a mediating quality of secondary depressive symptoms between hearing loss and cognitive performance. We found a significant association between subjective hearing ability in noise (APHAB) and severity of depressive symptoms, but no significant associations with cognitive performance. Hearing threshold (PTA) was not associated with depression or cognitive performance . There wTo our knowledge, the present study was the first to examine the mediator quality of depression in both older people and younger people with hearing loss.As expected, subjective APHAB hearing in noise was significantly related to the severity of secondary depressive symptoms, result of BDI II.Speech understanding performance in noise depends on complex central processing and cognitive functions –110. StuUnexpectedly, peripheral hearing ability  was not associated with the severity of depressive symptoms. Our results are consistent with those of Gobinath et al.  but not Furthermore, contrary to our expectations, we did not observe any significant correlation between four frequency hearing thresholds and cognitive performance. Instead, beyond the planned analyses, significant correlations were found between subjective hearing at quiet (APHAB “Ease of communication”) and cognitive performance  . Beyond We found no significant association between subclinical and clinical severity of depressive symptoms and cognitive performance. The results also do not support the models of Rutherford et al., Uchida et al., and Sharma et al., which hypothesize a direct relationship between depression and cognition of individuals with a hearing loss, see introduction , 27, 30.There is a well-established consensus that both hearing loss and cognitive decline tend to increase with age. Notably, hearing loss accelerates cognitive decline in older adults, a phenomenon that also has been observed in individuals with normal hearing , 21. GivIn addition, there seems to be a widespread assumption that the longer the hearing loss, the more severe the depressive status. In our exploratory analyses, we found no significant association between the years of hearing loss and the severity of depressive symptoms. To our knowledge, there are no other studies on this topic yet. That depressive moods can also occur at any age in people with hearing loss, the use of depression questionnaires such as the BDI are recommended in clinical work.In summary, our hypothesized model that depression mediates between hearing loss and cognition see  was not n = 8,094) to allow even small effects to become significant.n = 120) to achieve an effect size of small to medium size and an even larger sample for small effect sizes.Our results also seem to contrast with a recent study, finding that “depressive symptoms partially mediated the association between hearing loss and cognitive function  . DespiteBecause there were so many unexpected results, exploratory analyses were performed to find possible new paths for further investigation. We found that subjective hearing at quiet  was significantly related to phonemic fluency (Regensburger Wortflüssigkstest), cognitive flexibility (Trail Making Test-B), and visual episodic memory . The better the hearing ability during communication in quiet situations, the higher the cognitive performance.Fluency tests are among the tests of executive functioning or cognitive control. Studies show that these tests require not only controlled processing but also automatic processing –132. PreFollowing this interpretation, we hypothesize that individuals with hearing loss in adulthood will have problems in automatically retrieving words from the lexicon.Cognitive flexibility is defined as the ability to change “… perspectives or approaches to a problem, flexibly adjusting to new demands, rules, or priorities (as in switching between tasks)” .Five of the six questions of the APHAB EC subscale refer to verbal interactions. Verbal turn taking requires a very fast switch between the speaker’s perspective and the listener’s perspective, even in a quiet situation. This is complicated by the additional task of planning a response while listening and at the same time anticipating the communication partner’s perspective . AdditioFor people with hearing loss in particular this means that cognitive resources are tied up that are lacking elsewhere –140. ForWe suspect that this correlation with NVLT is not related to hearing (we found no correlation between PTA and NVLT) but to speech reading. In our clinical experience, many patients with severe and profound hearing loss and cochlear implant candidates can read speech because they rely on visual perception (viseme) to follow a conversation. Studies show that a combination of visual and auditory speech information improves speech recognition [without hearing loss –144]. OuThis appears to be the first time that hearing variables other than traditional hearing thresholds and speech recognition scores have been used in a study addressing cognition in individuals with hearing loss—planned and exploratory. The exploratory part is, in our view, a strength of this study, indicating that it seems reasonable to leave the beaten path of ever-larger study samples and small effects with presumably little clinical relevance. Thus, we turned a supposed disadvantage -our hypotheses could not be confirmed in all respects into an advantage and generated a list of new possible hypotheses (see above).n = 120 for a effect seize of an │r│ = 0.25). Extending the study period did not quite produce the expected effect because by the end of the study period, patient volume had not reached pre-Covid levels. A sample size of n = 61 may be sufficient to detect moderate to large effects in the associations between hearing and cognition, hearing and depression, and additionally depression and cognition. However, the subgroup of younger adults remained only small. The results of the younger group should therefore only be interpreted with caution.There are also limitations. This study was conducted during COVID-19 times, which resulted in a decrease of more than 50% in patient volume at the Hannover and Salzburg clinics. As a further consequence, fewer study participants could be recruited than planned, so that the necessary sample size for a mediation analysis was clearly missed  because of Covid is estimated to be low. In the statistics, the p’s of all outcomes in the planned analyses were controlled, as well as the p’s of the cognitive outcomes in the exploratory analyses. Note that the exploratory analyses were conducted to find new hypotheses, not to test hypotheses. Additionally, it cannot be excluded that the increased prevalence of depression and anxiety during COVID has minimally influenced the study outcomes of depression. Altogether, the risk of bias in selection, implementation, and statistics can be considered as still low.Concerning potential pandemic –147. ConThe inclusion and exclusion criteria were quite strict in our study. Our results may not be valid for individuals with hearing loss and a suspected cognitive impairment or with multiple comorbidities. In addition, the results on hearing in noise may be valid only for those who are not remotely able (even with hearing aids) to recognize speech in background noise . AdditiIn summary, the results of the planned and exploratory analyses do not support our original model see . We founFor further studies, it may be useful to consider not only commonly studied auditory variables such as hearing thresholds, but also auditory variables that may play an important role in hearing in everyday life and verbal communication and that have been little studied in research on cognitive decline in individuals with hearing loss to date. This can be done with questionnaires such as the APHAB or other surveys and methods that are part of the ecological momentary assessment (EMA) . Anotherper se, but more to different aspects of subjective limitations in everyday life due to hearing loss, regardless of age. Examples include distractibility and difficulty concentrating in noisy situations and communication problems in quiet situations that can quickly lead to frustration. These characteristics do not necessarily occur simultaneously in the same person and may affect patients differently depending on their occupation or other life situation.Our study results indicate that depressive symptoms and cognitive impairment are less related to hearing loss Reporting of this observational study was done in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement . A checkThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving humans were approved by Hannover (protocol number: 8419_BO_S_2019) and Salzburg (protocol number: 415-E/22489/2-2019). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.MH: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. LR: Investigation, Project administration, Writing – original draft, Writing – review & editing. LW: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing. BP: Conceptualization, Formal Analysis, Methodology, Software, Validation, Writing – review & editing. SR: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing. AI: Funding acquisition, Supervision, Visualization, Writing – original draft, Writing – review & editing.


Background: Congenital cytomegalovirus (cCMV) infection is the leading cause of non-hereditary sensorineural hearing loss in children. While about 10% of children reportedly display symptoms at birth, 85–90% of cCMV infection cases are asymptomatic. However, 10–15% of these asymptomatic infants may later develop hearing, visual, or neurodevelopmental impairments. This study aimed to evaluate the impact of cCMV infection on newborns’ hearing function with a particular emphasis on progressive and late-onset cases. Methods: This study is a retrospective chart analysis with longitudinal character and was conducted in two Italian centers: Center 1 (from 1 November 2007 to 31 December 2021) and Center 2 (from 1 January 2012 to 31 December 2021). Data collected included newborn hearing screening results, characterization of hearing loss , and audiological follow-up. Results: The cohort consisted of 103 children . In total, 28 children presented with hearing impairment; 71.4% (20 out of 28) of the cases of hearing loss were severe/profound, with 35.7% of the cases due to unilateral hearing loss. Out of twenty-eight, six experienced progression of hearing loss and four had late-onset hearing loss. Conclusions: In the absence of universal cCMV screening, hearing screening at birth for cCMV remains a critical factor for early diagnosis. A significant percentage of children affected by cCMV with normal audiological evaluations at birth is easily lost to follow-up. Close collaboration between neonatologists, pediatricians, and audiological services is fundamental to ensure timely diagnosis and treatment of cCMV-related hearing loss. Congenital cytomegalovirus (cCMV), regarded as the most prevalent congenital infection in humans, occurs in 0.2% to 6.1% of all live births . OtologiClinically, cCMV-related SNHL can be of varying severity, unilateral or bilateral, and can fluctuate, with periods of deterioration or improvement. It often manifests in early childhood , making Despite advancements in the field, it remains unclear which newborns are at risk of SNHL, especially in regard to late development. It was found that in newborns, the presence of petechiae at birth, periventricular cysts, or a seroconversion in the first trimester correlated with a higher risk of congenital hearing loss, though the significance of viral load as a risk factor remains unclear . The resAnother critical question is the necessity of extending hearing follow-up beyond six years of age, particularly in asymptomatic cases which contribute significantly to the overall disease burden associated with cCMV . DelayedThis study aims to evaluate the impact of cCMV infection on newborns’ hearing function, with specific attention to progression and late onset, across two centers in different Italian regions.This study is a retrospective chart analysis with longitudinal character. Within the framework of quality improvement, we collected data concerning the audiological follow-up of children affected by cCMV infection. In order to maintain patient confidentiality, all spreadsheets submitted to the principal investigator were fully anonymized and did not include any identifiable data relating to patients or caregivers. The study periods ranged from 1 November 2007 to 31 December 2021 (center 1) and from 1 January 2012 to 31 December 2021 (center 2). These start dates correspond to the implementation of the regional newborn hearing screening (NHS) programs, which are annually monitored by the respective regional health services. Children affected by cCMV infection who were referred from other birth hospitals to the audiological centers for evaluation were also enrolled in the study. The data from their clinical evaluation at birth were analyzed separately to minimize selection bias.Since 2012, following the guidelines of the Italian Society of Neonatology, CMV DNA research has consistently been performed in the following cases: preterm newborns , small-for-gestational-age babies , neonates born to CMV-infected mothers, babies showing abnormal prenatal cerebral aspects at ultrasound, babies with microcephaly (head circumference < 3° percentile), and those with persistent jaundice, thrombocytopenia, and/or neutropenia ,16. BegiBoth hospital centers, as standard practice, have a professional reference for monitoring cases of cCMV infection, aiming to facilitate the organization of multidisciplinary follow-up for affected children.Diagnosis of CMV infection was confirmed by testing urine samples using the shell vial assay (SVA). Cases of cCMV infection were defined as any newborn ≤ 14 days of age with a positive CMV urine test or with a positive polymerase chain reaction (PCR)-CMV test confirmed on Guthrie cards.Universal newborn hearing screening allows for the early detection of hearing impairment in neonatal infants. In both regions, the NHS program is based on a two-stage protocol and is differentiated according to the Joint Committee on Infant Hearing (JCIH) guidelines, for well babies and children with risk factors for hearing ,17.® Medical Incorporated, Taastrup, Denmark), which can register both otoacoustic emissions (OAEs) and Automated Auditory Brainstem Response (AABR).NHS testing was performed in the Neonatal Department by audiometry technicians or nurses using a Madsen AccuScreen device , TORCH infections, meningitis, encephalitis, family history of hearing loss, administration of aminoglycoside or other ototoxic drugs for more than 5 days, hyperbilirubinemia treated with exchange transfusion, neonatal intensive care unit (NICU) admission for more than 5 days, birth weight < 1500 g, and gestational age < 28 weeks  undergo For OAE detection, the tool utilizes a sampling frequency of 16 kHz. The stimulus is a ‘‘click’’ with an intensity ranging from 70 to 84 dB SPL (45–60 dB HL) and the intensity is automatically calibrated, depending on the volume of the ear canal. The stimulus frequency is approximately 60 Hz, and the frequency range lies between 1.5 and 4.5 kHz. For the execution of AABR, a click sequence with an intensity of 35 dB nHL is commonly employed, coupled with a pacing rate of 80 Hz and a sampling frequency of 16 kHz.Demographic data were obtained from the Regional Health services.According to protocol, all infants with cCMV undergo evaluation at 1, 3, and 6 months, then once every 6 months until 3 years of age, and then once a year until age 6. This follow-up schedule is modified in case of a hearing-impairment diagnosis. The surveillance path provides neonatal, pediatric, ophthalmologist, and neurological controls as indicated by Italian guidelines .® Synergy software. The parameters evaluated include the identification of I, III, and V wave peaks at various stimulus intensities, identification of the V wave threshold expressed in dB nHL, and measurements of the peak latencies of I, III, and V waves as well as the interaural difference of V wave latency (IT-5), expressed in ms. Thresholds of V wave identification ≤ 30 dB nHL, without a pathological delay in latency, are deemed indicative of normal results.Children undergo otoscopy, ABR, OAE, and tympanometry until they reach six months of age. The clinical ABR is recorded during spontaneous sleep, using MedelecAn acoustic immittance test is conducted in order to rule out potential over-estimations of the auditory threshold caused by middle or external ear dysfunctions, which are quite common in this age group.When children are between 8 and 12 months of age, a visual reinforcement audiometry (VRA) may be performed, depending on their compliance. This procedure is carried out through a two-channel diagnostic audiometer in Center 1  or using Astera by Madsen at Center 2.All families with normal results are advised, as per standard practice for children at risk of hearing loss, to bring their children to the hospital for a repeat audiological evaluation at the age of one year. Long-term follow-ups are conducted in cooperation with the family pediatricians.To better define the progression and late-onset cases, we decided to categorize  SNHL as The severity of hearing loss  was defined according to the WHO classification: mild (≥26 to <40 dB), moderate (≥41 to <55 dB), moderate-severe (≥56 to <70 dB), severe (≥71 to <90 dB), and profound (>90 dB) .During the study periods, Center 1 Hospital recorded 31,620 children, of which 31,545 underwent NHS, identifying 23 cases of cCMV infection. Similarly, Center 2 Hospital recorded 29,636 children with 29,616 undergoing NHS and 30 identified with cCMV infection. The NHS coverage was over 99% in both centers ,18.The trends of cCMV infection in newborns over time, calculated at both hospitals, are depicted in In Center 1, 62 children  were enrolled  were enrolled . Males represent 42% of the total population.We classified cases as “asymptomatic” only when they did not exhibit specific alterations, including hearing loss. Also considering late-onset cases, there were 28 children with varying degrees of hearing impairment out of 103 .All children who were highly suspected of hearing loss during the initial audiological examinations completed their follow-up, occasionally through other audiological services. Among the children who had normal auditory function at first examination after the NHS test (n = 79), follow-up visits were suspended within age 1 in 21 cases or age 3 years in 23 cases. In total, 43 children in this group did not complete the first three years’ follow-up. One child that presented late-onset hearing loss was lost at the first 3 years’ follow-up. Three children relocated within the first two months of life and continued their follow-up outside of the region.This study provides an analysis of the local clinical-epidemiological features of cCMV-related hearing loss across two different regional cohorts over a decade. Given that the literature on the demographic characteristics of children with cCMV-related hearing loss appears to be not extensive , it is iThe prevalence of cases of symptomatic cCMV infection was comparable across the two centers, falling within the range reported in high-income countries, while in other experiences, studies of cCMV prevalence have identified disparities among communities . This hoThe recent neonatal guidelines recommending cCMV infection screening at birth contributed to observing shifts in the prevalence of cCMV; both centers have reached a stabilization in the annual number of cases. It is necessary to underline that in the absence of targeted or universal cCMV screening, most children are identified due to symptoms suggestive of cCMV infection ; in thisAs indicated by the number of children affected by cCMV identified through NHS in our study, the synergy between the universal newborn hearing screening program and cCMV testing for asymptomatic infants who failed the OAE test allowed early diagnosis and the beginning of follow-up strategies .Most children of the cohort had a clear hearing screening response, with different percentages between the groups born in and out of the two hospitals. This is partly due to an increase in the number of children receiving CMV testing at birth, according to neonatal guidelines, most of whom were selected as preterm. A higher percentage of unclear responses in neonates coming from other facilities could be attributed to a selection bias, as many families receiving NHS pass results likely chose to avoid unnecessary travel to other towns, especially during the pandemic. Moreover, mild hearing loss cases are not easily identified through OAE and ABR, in the presence of prematurity or low birth weight, is not always reliable at the first response. A further complication in understanding cCMV-associated hearing loss is that cCMV can only be detected with high sensitivity when neonates are tested within the first three weeks of life. It can happen that infants are identified with SNHL when they are too old for direct testing to be specific for cCMV infection. In such cases, the only means to detect cCMV infection in children with SNHL is usually through newborn dried blood spot testing.In relation to hearing loss outcomes, our findings confirm that most early-onset cases are bilateral, as already reported . A signiA significant aspect to consider is the finding that the incidence of hearing loss increases with premature birth . AcquireSNHL can occur in 15% to 25% of all children with cCMV over the course of childhood . The perCurrently, as there is no virological marker to predict who will develop sequelae , a betteIn our experience, a small but not negligible percentage of children have developed unilateral or moderate bilateral hearing loss lately. In contrast, a recent study reported 2% of case-patients developed SNHL severe enough for them to be candidates for cochlear implantation . In thisIn both centers, there was a large number of subjects with normal hearing tests at birth that were lost at follow-up in the first three years of life. One child who presented late-onset hearing loss was among them, which could be due to the lack of perception of danger, especially in those cases in which children did not present other symptoms. Long-term follow-up of children with cCMV is essential to identify those with late-onset hearing loss . MoreoveThe pandemic did not allow the implementation of surveillance programs for well- known reasons, primarily fear and limitations in accessing the health services. However, more effort should be made to improve awareness of cCMV infection risks among the population , as longThis study has several limitations: the high rate of losses to audiological follow-up, the influence of the pandemic, the referral bias from outside the centers, and the relatively small number of cases. Moreover, due to the lack of universal screening in Italy, most asymptomatic cCMV infections with pass results at NHS remain undiagnosed.The strengths of this study include participation across multiple centers and the synergy between the NHS program and cCMV testing for asymptomatic infants who failed the OAE test. Another strength is the high coverage of NHS programs.Testing all newborns who do not pass hearing screening at birth for CMV, in the absence of universal screening for CMV, currently remains a key factor for early diagnosis of those cases that do not present other CMV-related symptoms. Hearing loss should be considered a symptom of cCMV infection even when isolated. In our experience, late-onset hearing loss cases were more likely to be unilateral and hearing loss appeared moderate when bilateral.A high percentage of children affected by cCMV with normal audiological evaluations at birth are easily lost at follow-up. Close collaboration between neonatologists, pediatricians, and audiological services is crucial to ensure timely diagnosis and treatment of cCMV-related hearing loss.


We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure‐tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable‐adjusted linear regressions. 75% of participants had hearing loss and 15% of participants had retinopathy. The association between retinopathy, microaneurysms, and blot hemorrhages with better speech‐frequency pure tone average was −2.81 , −4.75 (95% CI: −8.73 to −0.78), and −5.34 (95% CI: −8.68 to −2.00), respectively. The presence of retinopathy, microaneurysms, and blot hemorrhages was inversely associated with hearing loss. Further studies are needed to better understand the potential relationship between microvascular pathologies of the eye and ear. Age‐related hearing loss is prevalent and associated with several adverse health outcomes,Adults aged ≥70 years from the 2005 to 2006 cycle of NHANES were studied. Pure‐tone hearing thresholds in decibels (dB) hearing level were averaged to create speech‐frequency (0.5‐4 kHz), low‐frequency (0.5‐2 kHz), and high‐frequency (4‐8 kHz) pure‐tone averages (PTAs) in the worse‐hearing ear, with greater values indicating worse hearing. Hearing loss was defined as PTA>25 dB in the worse hearing ear. The presence of retinal pathologies, including retinopathy, arteriovenous nicking, focal arteriolar narrowing, microaneurysms, and blot hemorrhages for the worse‐seeing eye, were identified from graded fundus photographs. Sociodemographic characteristics, including age, sex, race, education, smoking history, and occupational exposure to loud noise, were collected in addition to health characteristics, including hypertension, diabetes, stroke, and body mass index.P < .05 was considered statistically significant. Statistical analyses were conducted using Stata version 17.0 (StataCorp LLC). The study protocol was approved by the National Center for Health Statistics Institutional Review Board; all participants provided written informed consent.Means and standard deviations or frequencies and percentages of demographics and health characteristics were examined. Multivariable‐adjusted linear regression was used to model the associations and was stratified by diabetes status. A 2‐sided 402536 (75.0%), and the mean speech‐frequency PTA was 37.4 dB HL (standard deviation: 15.3) in the worse‐hearing ear. The presence of retinal pathology ranged from 4.1%  to 17.9% (arteriovenous nicking). Participant characteristics by retinopathy in the worse eye are described in Supplemental Table 81536 participants (15.1%) had retinopathy, the distributions of speech‐frequency, low‐frequency, and high‐frequency PTAs were similar between those with and without retinopathy.The final sample comprised 536 participants , Table 1Differences in worse‐ear speech‐, low‐, and high‐frequency PTAs by worse‐eye retinal signs after adjusting for age, sex, race, education, smoking, and occupational exposure to noise, stratified by diabetes status, are shown in This study found an association of retinopathy, microaneurysms, and blot hemorrhages with better hearing; in other words, more retinal pathologies were associated with less hearing loss. This association was significant for low‐frequency PTA across all 3 retinal pathologies and borderline for the association between retinopathy and speech‐frequency PTA. This seemed to occur regardless of the presence of diabetes. Interestingly, there were no significant associations between retinal pathology and better high‐frequency PTA. In those without diabetes, however, focal arteriolar narrowing was associated with worse high‐frequency PTA.This study adds to the small body of literature investigating the relationship between retinal microvascular abnormalities and hearing loss. In the Blue Mountains hearing study, Liew et al performed retinal photography and PTA on individuals aged 54 and older. They found an association between retinopathy and low‐frequency hearing loss in women only.Alternatively, the inverse association between retinal pathologies and low‐ and speech‐frequency hearing loss identified here suggests a potential protective relationship between the visual and auditory systems, where the impairment of one system is associated with better performance in the other system.Recent studies have found an association between metformin, a medication commonly used to treat diabetes, and reduced risk of sensorineural hearing loss.We found an inverse association between retinopathy, microaneurysms, and blot hemorrhages with hearing loss, adding to the literature examining the association between retinal abnormalities and hearing loss in older adults. Further epidemiologic studies are needed to understand better the potential relationship between microvascular pathologies of the eye and ear.Zahra N. Sayyid, analyzed data and wrote the initial manuscript draft; Armaan F. Akbar, analyzed data and wrote the initial manuscript draft; Kening Jiang, designed the study and analyzed data; Jacob M. Pogson, designed the study; Nicholas S. Andresen, designed the study; Jennifer A. Deal, designed the study; Bryan K. Ward, designed the study. All authors contributed to the final draft of the manuscript.The authors declare that there is no conflict of interest.This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors.Supporting information.Click here for additional data file.


Bimodal cochlear implant (CI) listeners have difficulty utilizing spatial cues to segregate competing speech, possibly due to tonotopic mismatch between the acoustic input frequency and electrode place of stimulation. The present study investigated the effects of tonotopic mismatch in the context of residual acoustic hearing in the non-CI ear or residual hearing in both ears. Speech recognition thresholds (SRTs) were measured with two co-located or spatially separated speech maskers in normal-hearing adults listening to acoustic simulations of CIs; low frequency acoustic information was available in the non-CI ear  or in both ears. Bimodal SRTs were significantly better with tonotopically matched than mismatched electric hearing for both co-located and spatially separated speech maskers. When there was no tonotopic mismatch, residual acoustic hearing in both ears provided a significant benefit when maskers were spatially separated, but not when co-located. The simulation data suggest that hearing preservation in the implanted ear for bimodal CI listeners may significantly benefit utilization of spatial cues to segregate competing speech, especially when the residual acoustic hearing is comparable across two ears. Also, the benefits of bilateral residual acoustic hearing may be best ascertained for spatially separated maskers. Bimodal: electric stimulation in one ear and acoustic stimulation in the other ear; (2) EAS: electric stimulation and acoustic stimulation in the same ear; and (3) BiEAS: electric stimulation in one ear and acoustic stimulation in both ears.For many cochlear implant (CI) users, relaxed candidacy criteria, modified electrode designs, and improved surgical techniques have preserved residual acoustic hearing in non-implanted and/or implanted ears. Residual acoustic hearing provides detailed low-frequency information that can greatly benefit CI users under challenging listening conditions. For listeners with one CI, combined acoustic and electric hearing can be categorized into three listening conditions: (1) 13. However, some CI users do not experience significant benefits with Bimodal listening16 and others even experience interference18. Performance with EAS has been shown to be better than that with the CI alone, with even greater benefits observed for BiEAS19. The data from these previous studies indicate that the benefits of combined acoustic and electric hearing can be highly variable, possibly due to differences among individual CI users’ ability to combine acoustic and electric stimulation patterns within or across ears20.Bimodal listening has been shown to significantly improve speech and music perception relative to performance with the CI alone21 and segregation of spatially separated target and masker speech22. Dorman et al.21 found that sound localization scores were near chance level for bimodal CI users. Similarly, recent studies found little, no, or even negative spatial release from masking  for Bimodal CI listeners when head shadow effects were minimized by using symmetrically placed maskers23.In addition to providing useful low-frequency temporal fine-structure information, residual acoustic hearing in the non-implanted ear may provide some amount of binaural hearing in combination with the implanted ear. This low-frequency binaural hearing may be useful for sound localization and segregation of sound sources in space. However, for bimodal CI users, residual hearing in the non-implanted ear seems to have limited benefit for sound localization25 to better detect or recognize a target in the presence of competing sounds. For segregation of spatially separated speech, there are several benefits when listening with two ears over a single ear: head shadow , binaural summation , and binaural squelch 26. In general, bimodal hearing may not preserve important ITDs and/or ILDs due to timing differences  between the acoustic hearing ear and the CI ear30. For many Bimodal CI patients, residual hearing in the contralateral ear provides only limited information due to the severity of underlying hearing loss. Without high-frequency audibility in the non-implanted ear, Bimodal listeners cannot benefit from ILD cues in the higher frequency region; for CI users, ILDs are the dominant cue for spatial perception. Firszt et al.31 reported limited bimodal benefit for spatial perception in Bimodal listeners with sloping or severe-to-profound hearing loss in the high-frequency region , compared to Bimodal listeners who have broadband audibility in the non-implanted ear.Normal-hearing (NH) listeners can use various spatial cues, such as inter-aural time differences (ITDs), inter-aural level differences (ILDs), and/or some other binaural process 21, possibly due to the availability of high-frequency ILDs. While bilateral CI users may be able to use ILD cues for sound localization, the bilateral benefit for segregation of spatially separated target and masker speech are limited. This is especially true when head shadow effects are minimized by using symmetrically placed maskers23. The lack of SRM in these studies may be partly driven by possible inter-aural frequency mismatch due to different insertion depth and uneven nerve survival across ears. Indeed, recent bilateral CI simulation studies have shown that inter-aural tonotopic mismatch may negatively affect utilization of spatial cues34. Thomas et al.34 found that minimizing the inter-aural mismatch may significantly increase SRM, possibly because that inter-aural frequency matching may improve inter-aural coherence.Different from Bimodal CI patients, bilateral CI patients seem able to benefit from some spatial cues for sound localization35, resulting in some degree of tonotopic mismatch in the CI ear. Simulation studies have shown that tonotopic mismatch negatively affects the integration of acoustic and electric stimulation, regardless of whether residual acoustic and electric hearing were combined within an ear or across ears37. However, little is known about the effects of tonotopic mismatch on SRM for Bimodal listening.Similarly, Bimodal CI users’ difficulties in utilizing spatial cues may be partly due to the tonotopic mismatch between the acoustic input frequency and the electrode place of stimulation in the cochlea. In clinical fitting of Bimodal CI users, the lowest acoustic input frequency is typically much lower than the characteristic frequency associated with the most apical electrode position38 evaluated the effects of adjusting the low cutoff frequency (LCF) of the CI for CI-only and Bimodal CI listeners. They found that for the CI-only group, increasing the LCF reduced speech performance in both quiet and in noise. Similar results were observed for Bimodal listeners with limited acoustic hearing in the non-implanted ear (thresholds > 60 dB HL at 250 and 500 Hz). For Bimodal listeners with better hearing in the non-implanted ear (thresholds < 60 dB HL at 250 and 500 Hz), word recognition in quiet improved as the LCF was increased. Increasing the LCF likely reduced the tonotopic mismatch in the CI ear due to the relatively shallow electrode insertion depth.One approach to reduce tonotopic mismatch in the CI is to adjust the input acoustic range to match the characteristic frequencies associated with the electrode positions. For most bimodal CI users, this would involve increasing the lowest acoustic input frequency, truncating all information below the adjusted input frequency. The loss of low-frequency speech information in one CI ear with a tonotopically matched frequency allocation may be less deleterious for Bimodal CI users since low-frequency speech information would be available with the contralateral acoustic hearing. Fowler et al.21 reported significant improvements in localization for BiEAS users. The availability of residual hearing in both ears may allow the listeners to use ITD cues, thus resulting in improved sound localization. Gifford et al.40 showed significant speech recognition and subjective perceptual benefits for BiEAS compared to the Bimodal listening condition. They also found that limiting the CI bandwidth  yielded significant improvement for speech recognition in noise and subjective estimates of listening difficulty. These data suggest that tonotopic mismatch may significantly limit the benefit of BiEAS listening, consistent with previous simulation studies showing that EAS is highly sensitive to tonotopic mismatch36. Tonotopic matching within the CI appears to be important for utilization of acoustic hearing in the ipsilateral ear.While contralateral acoustic hearing may provide only limited benefit for perception of spatial cues in Bimodal CI users, Dorman et al.34 found limited benefit for tonotopic matching in simulations of bilateral CIs when maskers were co-located with the target speech, but a large benefit when maskers were spatially separated from the target. While tonotopic matching may be beneficial for Bimodal CI simulations when maskers are co-located with the target37, the benefit is less clear when the target and maskers are spatially separated. Similarly, the benefits of bilateral residual hearing for utilization of spatial cues to segregate competing speech have not been fully explored. Some studies have found BiEAS advantages over bimodal listening for spatialized noise44, but little is known regarding BiEAS advantages for competing speech, especially when target and maskers are spatially separated. Also, it is unclear how much residual hearing is needed in the implanted ear to be beneficial in conjunction with the contralateral residual hearing.Taken together, these previous studies suggest that tonotopic matching is important for Bimodal and BiEAS listening. However, most previous studies evaluated Bimodal and/or BiEAS speech performance in quiet, noise, or speech babble. The benefits of tonotopic matching on Bimodal and BiEAS listening for segregation of competing speech is not well studied. Also, the benefits of tonotopic matching may also depend on the target-masker spatial configuration. For example, Thomas et al.36. The second aim of the study was to evaluate the effects of tonotopic matching in electric hearing on segregation of competing speech for Bimodal listening. We expected limited benefit of tonotopic matching for co-located target and masker speech, but a larger benefit when target and masker speech were spatially separated, consistent with previous bilateral CI simulation data29. The third aim of the study was to evaluate the effects of bilateral residual acoustic hearing  on segregation of competing speech. We expected limited advantage for BiEAS over Bimodal listening for co-located target and masker speech, but a larger BiEAS advantage for spatially separated target and masker speech, as the bilateral residual hearing may provide useful low-frequency binaural cues44.In the present study, segregation of co-located or spatially separated target and masker speech was measured in NH adults listening to acoustic simulations of Bimodal and BiEAS CI signal processing in which the frequency allocation for the simulated CI was tonotopically matched or mismatched. The first aim of the study was to evaluate bimodal perception of target speech with co-located or spatially separated maskers. We expected that speech reception thresholds (SRTs) would be higher (poorer) with spatially separated than with co-located maskers due to poorer integration of acoustic and electric hearing across earsFigure SRM was calculated as the difference in SRTs between the co-located and spatially separated maskers. Figure 45 and real Bimodal CI users23. Tonotopic matching improved SRTs with co-located maskers, but less so with spatially separated maskers, resulting in reduced SRM. This finding is not consistent with previous data reported with simulated bilateral CIs34. SRM greatly improved for BiEAS listening when the amount of residual acoustic hearing was similar across ears, suggesting a great benefit for SRM with even a small amount of bilateral residual hearing . Gifford and Stecker44 found that the benefit of bilateral residual acoustic hearing was significantly correlated with BiEAS sensitivity to ILDs and ITDs, suggesting that SRM with BiEAS listening may be driven by perception of low-frequency spatial cues (more ITDs). The present data with the spatially separated maskers are consistent with previous studies that found significant SRM with spatialized noise for BiEAS CI simulations43. Note that mean SRM with spatialized noise was larger than with the present two-talker speech maskers (5.5 dB), possibly due to the increased susceptibility to informational masking with CI signal processing47. Combined with the spatial perception data from Dorman et al.21 and Gifford and Stecker44, the present data shows the advantage of preserving residual acoustic hearing in both ears to support segregation of spatially separated target and masker speech.Little SRM was observed for the simulated Bimodal listening conditions, consistent with data reported in Bimodal CI simulations48. The present Bimodal adapted condition likely overestimated the degree of adaptation for real bimodal CI users.For both the Bimodal adapted and Bimodal clinical conditions, the acoustic-to-electric frequency allocation maximized the speech information delivered to the simulated CI. As with clinical fitting of Bimodal CI users, the Bimodal clinical condition introduced both an intra-aural and an inter-aural tonotopic mismatch. The Bimodal adapted condition represented long-term perceptual adaptation to this mismatch . As such, it also represented the upper limit of Bimodal performance, assuming complete adaptation. Previous studies have shown that Bimodal CI users can partially adapt to tonotopic mismatch, but adaption is generally incomplete49, the frequency allocation can be adjusted to match the electrode locations in the cochlea . In this case, the combined acoustic and electric hearing across ears would be tonotopically matched, with little spectral overlap between the stimulation modes. Interestingly, there was no significant difference in SRTs between the Bimodal match and Bimodal adapted conditions, despite the very different CI acoustic input frequency ranges. The data suggest that the loss of speech information in the CI with a tonotopically matched frequency allocation may have only limited impact on speech performance for co-located maskers, because the lost speech information in electric hearing would be represented by the residual acoustic hearing. The similarity between the Bimodal match and adapted conditions also suggests that spectral overlap may not be an issue when there is no tonotopic mismatch in electric hearing, consistent with previous studies44. Compared to the Bimodal clinical condition, in which there was a tonotopic mismatch, SRTs were significantly lower (better) with the Bimodal match and adapted conditions.If complete adaptation to the clinical frequency allocation is not possible34, who reported that SRM was similar for tonotopically-matched or -mismatched bilateral CI simulations. The differences in speech bandwidth between residual acoustic hearing and the CI may partly explain these different outcomes.With co-located or spatially separated maskers, mean SRTs were significantly lower for the Bimodal match than for the Bimodal clinical condition. However, the mean improvement in SRTs with the spatially separated maskers in the Bimodal match condition was only 1.8 dB, half of that observed with the co-located maskers (3.9 dB). Accordingly, the mean SRM was significantly poorer for the Bimodal match (− 2.6 dB) than for the Bimodal clinical conditions (− 0.6 dB). This result is different from Thomas et al.45 and real Bimodal CI users23.With the co-located maskers, mean SRTs improved from 9.3 dB with the Bimodal clinical to 5.5 dB with the Bimodal adapted condition, an improvement of 3.8 dB. Similarly, with the spatially separated maskers, mean SRTs improved from 9.8 dB with the Bimodal clinical to 5.8 dB with the Bimodal adapted condition, resulting in a similar improvement of 4.0 dB. Again, the acoustic input for the Bimodal clinical and adapted conditions maximized the speech information, with tonotopic mismatch for the clinical condition but no tonotopic mismatch for the adapted condition. While little SRM was observed for either condition, bimodal SRM was not affected by tonotopic mismatch. This suggests that Bimodal CI users may not benefit much from spatial cues even if they are able to completely adapt to tonotopic mismatch. The present Bimodal simulation data are generally consistent with previous data from Bimodal CI simulations36, who found significantly better integration efficiency for vowel recognition in quiet when tonotopically matched electric hearing was combined with residual hearing in the ipsilateral rather than the contralateral ear. Differences in the speech tests and listening conditions may partly explain this discrepancy in results. A very different pattern was observed for spatially separated speech maskers. Mean SRTs improved from 8.0 dB with no ipsilateral residual hearing  to 5.3 dB with ipsilateral residual hearing up to 300 Hz (BiEAS low) and to − 0.5 dB with ipsilateral residual hearing up to 600 Hz (BiEAS high). This finding is consistent with Fu et al.36, despite differences in speech tests and listening conditions. The improvement was likely driven by the better spatial perception with BiEAS listening44. In the present study, bilateral acoustic hearing up to 300 Hz was not tested, so it is difficult to know how the bandwidth and/or asymmetry in residual acoustic hearing may affect segregation of spatially separated target and masker speech with BiEAS listening.When there was no tonotopic mismatch, adding ipsilateral residual acoustic hearing provided no significant advantage for Bimodal SRTs when target and masker speech were co-located. This finding is not consistent with Fu et al.50 was based on threshold detection in NH listeners. Hearing loss and subsequent amplification by hearing aids may result in substantial distortion to Greenwood’s50 tonotopic map. In the present study, there was no simulation of hearing loss for the residual acoustic hearing; instead, the residual acoustic hearing was simulated by simply band-pass filtering the acoustic input between 100 and 300 Hz or 100 Hz and 600 Hz. This would not capture the degree of distortion in the residual acoustic hearing that is likely experienced by real Bimodal CI users. As such, the present simulation of residual acoustic hearing is probably a “best-case scenario” that may overestimate the contribution of residual hearing.There are limitations to the current study which should be noted. A critical consideration is that the tonotopic map outlined by Greenwood39 found that greater overlap between the acoustic component and the CI allocation provided greater EAS benefit for speech performance than with the clinically recommended settings, where overlap was minimized. In the present study, the Bimodal match condition (where there was no frequency overlap between acoustic and electric hearing) produced much poorer SRM than that did the Bimodal clinical or adapted conditions. While these listening conditions were different from the EAS condition in Gifford et al.39, both suggest that some degree of frequency overlap between acoustic and electric hearing may benefit combined acoustic and electric hearing. Further studies are needed to better understand potential tradeoffs between tonotopic mismatch and frequency overlap between acoustic and electric hearing, within and across ears.Another limitation is the sharp filter cutoffs in the simulated CI and residual acoustic hearing, which minimized interactions between acoustic and electric hearing within the CI ear. However, acoustic and electric stimulation may have significant overlap due to channel interaction. Gifford et al.The present simulation data suggest that hearing preservation in the implanted ear may significantly benefit Bimodal CI listeners’ utilization of spatial cues when segregating competing speech, especially when the amount of residual acoustic hearing is comparable across ears. The benefits of residual acoustic hearing in the implanted ear may be best ascertained in Bimodal CI listeners when target and masker speech are spatially separated. The present simulation data with co-located or spatially separated competing speech maskers adds to previous studies with real Bimodal and BiEAS CI users typically tested in quiet, noise, or speech babble. Bilateral low-frequency residual acoustic hearing may increase release from informational masking in CI users.In compliance with ethical standards for human subjects, written informed consent was obtained from all participants or their legal guardians before proceeding with any of the study procedures. The study and its consent procedure were approved by the Institutional Review Board of the University of California, Los Angeles (UCLA IRB#19-000722 and IRB#18-001604) and this research was conducted in accordance with the principles of the Declaration of Helsinki and its later amendments.Twelve NH adults  participated in the study. All participants had pure tone thresholds < 25 dB HL at all audiometric frequencies between 250 and 8000 Hz. All were native speakers of American English. In compliance with the ethical standards for human participants, written informed consent was obtained from all participants before proceeding with any of the study procedures.12 and consisted of a total of 50 words from five categories , each of which contained 10 monosyllable words. Target sentences were generated by always selecting the Name “John” (the target sentence cue word), and then randomly selecting from the 10 words in each of the remaining categories. All 50 words for the target sentence were produced by a male talker and the mean fundamental frequency (F0) across all 50 words was 106 Hz. Similarly, two different masker sentences were generated by randomly selecting words from each of the categories. For each masker sentence, words were randomly selected to be different from the target sentence as well as from the other masker sentence. Thus, during each test trial, target and masker sentences were comprised of different words. All 50 words for the two masker sentences were produced by two different male talkers (mean F0s: 97 Hz and 128 Hz). A more detailed description regarding the test materials can be found in previous related studies37. The duration of the words used to generate the target and masker sentences varied slightly across categories and talkers. As such, after generating the target and masker sentences, the masker sentence duration was normalized in real-time to have the same duration as the target without affecting pitch using SoundTouch software (https://gitlab.com/soundtouch/soundtouch).The matrix-style test materials were drawn from Sung Speech Corpus51. The target sentence always originated directly in front of the listener (0° azimuth), and the two masker sentences were either co-located with the target (0°) or spatially separated from the target (± 90°).All target and masker stimuli were generated in real-time and delivered to circumaural headphones (Sennheiser HDA 200) via audio interface (Edirol UA-25EX) connected to a mixer (Mackie 402). Non-individualized head-related transfer functions (HRTFs) were used to create a virtual auditory space for headphone presentation of the stimuli50. The temporal envelope from each analysis band was extracted using half-wave rectification and low-pass filtering (cutoff frequency = 160 Hz). Next, the extracted envelopes were used to modulate the amplitude of sinewave carriers. The distribution of the carrier sinewaves assumed a 20-mm electrode array with 16 electrodes linearly spaced in terms of cochlear place. The simulated insertion depth was fixed at 24 mm, relative to the base. The frequency allocation used in the vocoder for the CI ear was manipulated to simulate three distinct speech processors:50. However, there was an intra-aural tonotopic mismatch within the CI ear, as well as an inter-aural low-frequency mismatch between the contralateral acoustic hearing ear and the CI ear.Bimodal clinical: The input frequency range was 200–8000 Hz while the output frequency range was upshifted to 610–11,837 Hz based on the expected spiral ganglion characteristic frequency associated with the simulated insertion depth (24 mm from the base) and electrode length (20 mm) according to the Greenwood’s functionBimodal adapted: Both the input acoustic frequency range and output frequency range were 200–8000 Hz. This bimodal condition was used to simulate long-term adaptation to tonotopic mismatch. All speech information was presented to the CI ear. Here, there was no intra-aural tonotopic mismatch within the CI ear and no inter-aural mismatch between the acoustic ear and the CI ear. Performance in this condition represented the upper limit for traditional Bimodal listening.50. Low-frequency speech information below 610 Hz was truncated in the CI ear, but was preserved in the contralateral acoustic ear. Here, there was no intra-aural tonotopic mismatch within the CI ear and no inter-aural mismatch between the acoustic ear and the CI ear. There was also no frequency overlap between acoustic and electric hearing.Bimodal match: Both the input acoustic frequency range and output frequency range were 610–11,837 Hz. The input frequency range was tonotopically matched to the expected spiral ganglion characteristic frequency associated with the simulated insertion depth (24 mm from the base) and electrode length (20 mm), according to Greenwood’s functionIn each test trial, the target and masker sentences were first generated according to the specified target-to-masker ratio (TMR). The TMR was calculated according to long-term root-mean-squared (RMS) power between the target sentence and each masker sentence. Note that the masker sentences were equalized in terms of long-term RMS level before the TMR calculation. The target and masker sentences were first processed by the HRTF and then mixed independently into the left and right channel. The mixed target and masker sentences in the left channel were bandpass filtered with a cutoff of 100–600 Hz and a slope of − 240 dB/octave to simulate residual acoustic hearing in the non-implanted ear. The mixed target and masker sentences in the right channel were processed by a 16-channel sine-wave vocoder to simulate electric hearing with the CI. For the sine-wave vocoder, the signal was first processed through a high-pass pre-emphasis filter with a cutoff of 1200 Hz and a slope of − 6 dB/octave. The input frequency range was then divided into 16 frequency analysis bands according to the experimental acoustic-to-electric frequency allocation using 4th-order Butterworth filters that were distributed according to Greenwood’s frequency-place formulaBiEAS low: The simulated residual hearing in the non-implanted ear was 100–600 Hz. The simulated residual hearing in the CI ear was 100–300 Hz.BiEAS high: The simulated residual hearing in the non-implanted and implanted ears was 100–600 Hz.The mixed target and masker sentences in the right channel were also bandpass filtered to simulate the residual acoustic hearing in the implanted ear. The amount of residual hearing in the implanted ear was manipulated to simulate two additional speech processors. For both speech processors, the parametric variations in electric hearing were same as bimodal match condition.Figure 52. Participants were instructed to listen to the target sentence (cued by the name “John”) and then click on one of the 10 response choices for each of the Number and Color categories; no other selections could be made from the remaining categories, which were greyed out. The target level was fixed at 65 dBA. The TMR was globally adjusted from trial to trial by varying the levels of each of the male maskers by the same amount according to the correctness of the response. If the participant correctly identified both the target Number and Color keywords, the TMR was reduced; if not the TMR was increased. The initial step size was 4 dB for the first two reversals in TMR, and the final step size was 2 dB. The SRT was calculated by averaging the last six reversals in TMR. The 10 listening conditions  were randomized within a test block and 2–3 blocks were tested for each participant; SRTs for each condition were averaged across blocks. Participants were given no practice or previews prior to the testing sessions, and no feedback was provided during testing. All testing was completed in a single session with short breaks between test blocks.Testing was performed in a sound-attenuating booth. SRTs were measured using an adaptive procedure (1-up/1-down) that produced a 50% correct identification of both keywords. The procedure was similar to a coordinate response matrix testSRT data were analyzed using an RM ANOVA, with listening condition and masker spatial configuration as within-subject factors. SRM data were analyzed using an RM ANOVA, with listening condition as the within-subject factor. Significance was defined as p < 0.05. Bonferroni correction was applied to post-hoc pairwise comparisons. RM ANOVAs were performed using SPSS . All figures were generated using Sigmaplot software (Version 14).Supplementary Information.


To determine if there is a difference in hearing outcomes or stimulation levels between Advanced Bionics straight and precurved arrays.Retrospective chart review across three implant centers.Tertiary centers for cochlear and auditory brainstem implantation.One hundred fifteen pediatric and 205 adult cochlear implants (CIs) were reviewed. All patients were implanted under the National Institute for Health and Care Excellence 2009 guidelines with a HiRes Ultra SlimJ or Mid-Scala electrode array.Hearing preservation after implantation, as well as CI-only listening scores for Bamford-Kowal-Bench sentences were compared 1 year after implantation. Stimulation levels for threshold and comfort levels were also compared 1 year after implantation.Hearing preservation was significantly better with the SlimJ compared with the Mid-Scala electrode array. Bamford-Kowal-Bench outcomes were not significantly different between the two arrays in any listening condition. Stimulation levels were not different between arrays but did vary across electrode contacts. At least one electrode was deactivated in 33% of implants but was more common for the SlimJ device.Modern straight and precurved arrays from Advanced Bionics did not differ in hearing performance or current requirements. Although hearing preservation was possible with both devices, the SlimJ array would still be the preferred electrode in cases where hearing preservation was a priority. Unfortunately, the SlimJ device was also prone to poor sound perception on basal electrodes. Further investigation is needed to determine if deactivated electrodes are associated with electrode position/migration, and if programming changes are needed to optimize the use of these high-frequency channels. A cochlear implant (CI) is an implantable hearing device that provides sound through electrical stimulation. The design of a CI electrode array influences where the device is located within the cochlea and can impact the amount of stimulation (current) required to reach audibility –3, the rPrecurved arrays are designed to curl toward the modiolus in an effort to keep electrical stimulation close to the remaining auditory-neural tissues –9. This In contrast, lateral wall (LW) arrays are “straight” electrodes designed to sit away from the modiolus. They are farther from the neural tissue and may require more current for auditory stimulation ,19,20. HConventional evidence favors PM arrays for “traditional” more severely deafened CI candidates and LW arrays for those with more hearing . HoweverWith this retrospective analysis of our implanted population, we compared the Advanced Bionics  SlimJ and Mid-Scala electrodes to determine if conventional evidence holds true for these devices. Both arrays have demonstrated structural preservation in temporal bones, which is important for HP . HoweverFor modern straight and precurved Advanced Bionics arrays, we aimed to investigate 1) if there was a difference in HP, 2) if hearing outcomes supported conventional choices for PM versus LW arrays, and 3) if the Mid-Scala device required lower current levels than the SlimJ device because of its position closer to the modiolus. We hypothesized that HP would be superior with the LW electrode, and that electrical hearing would be better with the precurved electrode.A multicenter retrospective chart review across three UK CI centers was conducted for 63 pediatric patients (115 implants) and 204 adult patients (205 implants) implanted between January 2016 and November 2018 . There was no significant difference between devices for preoperative hearing at 250  or 500 Hz , indicating that preoperative hearing did not bias electrode selection.The distribution of preoperative hearing at 250 and 500 Hz was normal for SlimJ and Mid-Scala recipients (Degree of HP (% HP) and HP classification at low frequencies was calculated using a modified HEARRING group formula ,36,37, bBamford-Kowal-Bench (BKB) sentence (% words correct) scores were collected for CI-only listening conditions 1 year after implantation (12 ± 4 mo) for adult recipients. Scores were collected for BKB sentences when listening to a male speaker in quiet, female speaker in quiet, male speaker in noise, and female speaker in noise conditions. All speech in noise testing used pink noise at +10 dB signal-to-noise ratio.a) hearing likely to benefit from EAS (≤70 dB HL) and (b) hearing unlikely to benefit from EAS (>70 dB HL). Because of the limited use of combined stimulation, comparisons for active EAS components could not be made.To check if more severely deafened CI candidates should receive the precurved array and those with better hearing the LW array, BKB scores were compared based on preoperative hearing for 250 and 500 Hz separately. Patients were grouped into the following ranges for each frequency: (http://links.lww.com/MAO/B772), indicating acceptable threshold levels in most cases. Thresholds were measured at centers 1 and 2, but left at default (10% of comfort levels) for most adults at center 3. Threshold levels were also set to default for most pediatric patients at centers 1 and 2.Threshold level, comfort level, pulse width, and number of deactivated electrodes were collected 1 year after implantation. Threshold and comfort levels were presented in charge units (cu), as listed in the SoundWave software . This allowed for direct comparison of clinical MAPs, as cu already incorporates pulse width [cu = (microAmps × pulse width)/79]. Levels were also converted to charge [nC/phase = (cu × 79)/1000] to enable comparison with other manufacturers. Sound-field aided thresholds 1 year after implantation confirmed that sound detection was within the clinically recommended range  for Patients who did not use spoken language as their primary mode of communication  were excluded from all comparison. Patients were also removed if they did not attend their 1-year appointment , or showed signs of V1 failure ,41 (6 Slt test), HP , overall BKB outcomes (Mann-Whitney U test), and variance in BKB outcomes (Levene test). In addition, interactions were checked for BKB outcome using univariate analysis of variance (ANOVA), with factors electrode  and hearing threshold (≤70 versus >70 dB HL) for 250 and 500 Hz separately. Distribution of threshold and comfort levels were tested separately using repeated-measures ANOVA, with factors channel  and implant center . Threshold and comfort levels were significant when tested against the Mauchley test of sphericity, therefore, the Greenhouse-Geisser correction was used. Finally, the number of deactivated channels was analyzed with the χ2 test.All tests were completed using SPSS 26 statistics package  . Normalip < 0.001). Overall, degree of HP was better for the SlimJ device .Postoperative hearing was measured for 131 ears . Degree of HP was not normally distributed . The electrode effect showed better HP with the SlimJ device for EAS candidates , but no significant difference for non-EAS candidates . Despite at least some HP in most cases, EAS was active for only seven adult and eight pediatric implants 1 year after implantation.The degree of HP was better for EAS candidates (average HP: 57%) compared with non-EAS candidates (average HP: 43%), with a significant effect of electrode (Mann-Whitney p ≤ 0.007) and were limited by ceiling effects . However, there was a greater spread in performance with a male speaker in noise for the SlimJ device . However, there was greater variability in outcomes for the male speaker with the SlimJ electrode , preoperative hearing was compared separately for 250 and 500 Hz. For each frequency, BKB results were compared between EAS candidates (≤70 dB HL) and non-EAS candidates .Regardless of electrode, patients with preoperative hearing ≤70 dB HL had better BKB scores when listening to a male speaker in quiet and in noise. This held true for 250 and 500 Hz , where performance was worse for SlimJ recipients, but only when preoperative hearing was >70 dB HL at 500 Hz . A similar trend was observed for 250 Hz but was not significant . However, this interaction is likely attributed to six SlimJ recipients who experienced significant difficulty when listening in noise . Unfortunately, because of limited sample size, the female speaker in noise condition could not be analyzed. Regardless of electrode, patients with better preoperative hearing at 250 or 500 Hz tended to have higher BKB scores only when listening to the male speaker.When listening to a female speaker in quiet, BKB scores were similar regardless of preoperative hearing and electrode . This trend was common across all centers, as well as for adult and pediatric recipients . Basal electrodes were most frequently deactivated for both arrays. The most common reason was inadequate sound perception, including poor sound detection or loudness growth .One-year programming MAPs were collected for 131 SlimJ and 133 Mid-Scala implants. Deactivated electrodes were more common for the SlimJ device, with 60 (46%) SlimJ and 42 (32%) Mid-Scala devices having at least one electrode turned off (http://links.lww.com/MAO/B773). For adults , and comfort level . Similarly, there was an interaction for comfort level between channel and array , where arrays had different comfort levels, but only for basal channels. However, to address our question, overall current requirements were similar for both devices.Average threshold and comfort levels are shown separately for each center because of differences in programming  and comfort level . Poor perception may be related to physiological factors, such as anomalies in cochlear morphology or duration of deafness and survival of the spiral ganglion cells (The most common reason in our series for electrode deactivation was poor auditory perception (Supplementary Table 2, on cells , or elecon cells . In addion cells . ImportaThis series reviews the performance of Advanced Bionics Ultra V1 implants for which a known fault exists . This faThe tests used for hearing outcomes may not be sufficiently sensitive to detect differences in performance and listening effort. BKB sentences are the clinical standard in the United Kingdom; however, they offer greater context for top-down processing and are prone to ceiling effects. We are also unable to elaborate on how scalar location affects programming without access to higher-resolution imaging.HP was possible with both modern Advanced Bionics array designs but continues to be better with the straight electrode. Overall hearing outcomes were similar between the SlimJ and Mid-Scala arrays. Regardless of array, patients with preoperative hearing within EAS criteria performed better than more traditional CI candidates. “Traditional” CI candidates did not benefit more from a precurved compared to a straight electrode. However, there was less variation in performance for difficult listening conditions with the Mid-Scala device. Further information is required to understand the variability in basal electrode stimulation to determine if programming adjustments are required to optimize performance.