The Rapid Assessment of Hearing Loss (RAHL) survey protocol aims to measure the prevalence and causes of hearing loss in a low cost and rapid manner, to inform planning of ear and hearing services. This paper reports on the first field-test of the RAHL in Gao’an County, Jiangxi Province, China. This study aimed to 1) To report on the feasibility of RAHL; 2) report on the estimated prevalence and causes of hearing loss in Gao’an.A cross-sectional population-based survey was conducted in September–October 2018. Forty-seven clusters in Gao’an County were selected using probability-proportionate-to-size sampling. Within clusters, compact segment sampling was conducted to select 30 people aged 50+. A questionnaire was completed covering sociodemographics, hearing health, and risk factors. Automated pure-tone audiometry was completed for all participants, using smartphone-based audiometry (hearTest), at 0.5, 1, 2, 4 kHz (kHz). All participants had their ears examined by an Ear Nose and Throat (ENT) doctor, using otoscopy, and probable causes of hearing loss assigned. Prevalence estimates were age and sex standardised to the Jiangxi population. Feasibility of a cluster size of 30 was examined by assessing the response rate, and the proportion of clusters completed in 1 day.1344 of 1421 eligible participants completed the survey (94.6%). 100% of clusters were completed in 1 day. The survey was completed in 4.5 weeks. The prevalence of moderate or greater hearing loss  was 16.3%  and for any level of hearing loss (pure-tone average of > = 26dBHL in the better ear) the prevalence was 53.2% . The majority of hearing loss was due to acquired sensorineural causes . Overall 54.0% of the population aged 50+  are in need of diagnostic audiology services, 3.4% were in need of wax removal (7000 people), and 4.8% were in need of surgical services (9500 people). Hearing aid coverage was 0.4%.The RAHL survey protocol is feasible, demonstrated through the number of people examined per day, and the high response rate. The survey was completed in a much shorter period than previous all-age surveys in China. Some remaining challenges included assignment of causes of probable sensorineural loss. The data obtained from this survey can be used to scale-up hearing services in Gao’an. In 2018, the World Health Organization (WHO) estimated that 466 million people globally had disabling (moderate or greater) hearing loss - 106 million more than the previous estimate from 2012 . This inGlobal estimates must be interpreted in light of the very limited data on population prevalence, and causes of hearing loss, particularly from LMICs. Evidence used to calculate current global estimates includes less than 50 surveys of hearing loss, the first conducted in 1982 and most recent in 2006. The most recent survey in sub-Saharan Africa was conducted in 2003, more than 15 years ago. Out of the 46 countries in sub-Saharan Africa, 11 surveys of hearing loss have been conducted (i.e. less than a quarter of countries), and only eight of these were all-age population-based surveys. In China, a country of over 1.3 billion people, one previous all-age survey has been conducted, with a small number of others focusing on particular age groups  , 8. ThesThe substantial impact of hearing loss on communication, speech and language development has been well-described . HearingPrevious research has described the difficulties with conducting all-age population-based surveys of hearing loss, which includes high cost equipment, lack of human resources, large sample sizes required and lack of global attention , 22, 23.To report on the feasibility of conducting the RAHL surveyTo estimate the prevalence and causes of hearing loss amongst people aged 50+ in the population of Gao’an, China.The main purposes of this study were:The RAHL methodology has been developed through an iterative process. Firstly, we conducted a secondary data analysis of previous all-age population-based surveys conducted in India  and CameThe RAHL is a population-based cross-sectional household survey. The target population is people aged 50 + .The sample size is calculated based on the expected prevalence of moderate or greater hearing loss in people aged 50+, desired confidence of 95%, 20% precision around the estimate, a design effect (DEFF) of 1.5 (conservative estimate based on data from India and Cameroon), and response rate of 90% .A two-stage sampling procedure is used to select firstly clusters, and then individuals within selected clusters. This methodology has been widely used in the RAAB survey developed by the International Centre for Eye Health at the London School of Hygiene & Tropical Medicine . In the One enumerator: to enumerate eligible participants, obtain informed consent, and complete a sociodemographic questionnaireTwo hearing testers: to complete hearing screening. The pilot in Malawi found that with only one hearing tester per team, less than 20 people can be seen per day. In order to reach an adequate cluster size (i.e. at least 30 people), two testers were required. The diagnostic accuracy study in Malawi found that non-specialist health workers can be trained to accurately assess hearing [ hearing .One ear examiner: to complete an ear examination using otoscopy and assign causes (Ear Nose and Throat (ENT) specialist). Pilot work in Malawi suggested at least an ENT clinical officer  is required to be in the field [he field .Based on the pilot in Malawi, the team makeup for the RAHL includes:All team members are trained for at least 5 days prior to undertaking the RAHL on study procedures, ethical considerations, and clinical tests. This training includes an inter-observer variation (IOV) study to check consistency in diagnosis across assessors.All participants complete a general questionnaire covering demographics, household characteristics and assets-ownership, self-reported hearing loss, and risk factors for hearing loss.Each participant has their hearing screened by a trained person using a validated mobile-based automated audiometry system, hearTest (hearX group) , 30. ThrAll participants have their ears examined using otoscopy by an ENT specialist or equivalent and diagnosis made. Outcomes include normal ear examination, otitis externa (OE), impacted wax (IW), foreign body (FB), acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) – wet perforation, COM – dry perforation, and other middle ear condition.Probable causes of hearing loss assigned for those with hearing loss. Outcomes include OE, IW, FB, AOM, OME, COM – dry, COM – wet, other middle ear, acquired sensorineural, congenital sensorineural, or mixed.Those with any level of hearing loss or ear disease are asked about previous care seeking for the condition.Simple conditions  are treated in the field, and more complex conditions are referred to the nearest services which are identified in advance of the survey.In households with eligible individuals, a paper-based household roster is completed, recording basic information about eligible members of the household. Mobile-based data collection, using the platform Open Data Kit (ODK), is used to collect questionnaire data. Data collection includes the following steps:Assigning the exact cause of hearing loss is difficult, even in high-resource settings, with all available clinical tools. There is always a trade-off between the level of accuracy and costs. The more detail needed, the higher the survey costs. Given the complexities with assigning a cause the ear examiner can only assign the “probable” causes. This survey protocol takes a pragmatic approach that is feasible in the field, allowing appropriate conclusions to be drawn about what the key service needs are for the population.To help standardise the assignment of probable causes related to the middle and outer ear , an algorithm was developed using a review of the literature, expert consultation, and a pilot-test in a clinic-based study in Malawi see  1. The aFor causes related to the inner ear , the assignment is based on clinical history of hearing loss and risk factors (obtained from the questionnaire), the results of the ear examination, and hearing test. Sensorineural causes are grouped in to acquired or sensorineural.Causes are grouped in to broad type categories, either probable conductive, sensorineural, or mixed. If the ear examination is abnormal and hearing loss present, it is assumed that hearing loss is conductive. If the ear examination is normal and hearing loss is present, it is assumed that the hearing loss is sensorineural. A decision support system is programmed in to the ODK questionnaire to prompt the clinician on the probable type. This is based on the results of the ear examination. At this stage, the clinician can agree or disagree with the suggested type, and if they disagree, a reason for this specified.Table Hearing aid coverage was estimated using the following calculation:a is the number of participants with any level of hearing loss , probable mixed or sensorineural in nature in both ears, who report that they own a hearing aid (met need);b is the number of people with any level of hearing loss , probable mixed or sensorineural in nature in both ears, who report not owning a hearing aid (unmet need)Where,We recognise that some people with conductive hearing loss may benefit from hearing aids, however we assume the medical or surgical intervention would precede the rehabilitation.Prevalence of hearing loss: The WHO definitions of hearing loss are used, which are based on pure-tone average of 0.5, 1, 2, and 4 kHz in the better ear. Estimates are obtained for: “disabling hearing loss” referred to in this paper as moderate or greater hearing loss (> = 41dBHL), any level of hearing loss (> = 26dBHL), and degree of hearing loss  [greater) , 39.Prevalence of ear disease: The outcome of the ear examination was analysed to obtain the prevalence of ear disease, regardless of the presence of hearing loss.Probable causes of hearing loss: in each ear amongst those with any level of hearing loss. The options for the causes of hearing loss are provided in Table Need and coverage of services: based on the diagnoses made  provides ear and hearing care services. Hearing aid fittings, and surgeries require referrals to Nanchang, the capital city of Jiangxi province (one-hour drive from Gao’an). The research was conducted in collaboration with Gao’an People’s Hospital by two teams.Field testing of the RAHL was conducted in Gao’an, Jiangxi province, China in September–October 2018. Gao’an is a county-level rural city, covering an area of 2430 kmThe sample size for this setting was determined to be 1412 based on a conservative expected prevalence of 10%. Thus 47 clusters were required to meet the desired sample size. Clusters (villages) were selected from the 2017 Jiangxi census (sampling frame), using probability-proportionate-to-size sampling.Obtaining maps for segmentation proved difficult. The villages, particularly in urban areas were densely populated, with most people living in apartments in multi-story buildings. Instead of mapping, lists of “natural villages”, (sub-villages) and their population sizes were obtained from community leaders. These natural villages were numbered, and one area randomly selected as the segment using a random number generator. Each sub-village was approximately the same size as our desired segment size. If the selected sub-village was too large, it was further segmented on arrival in the segment with the assistance of a community leader. If it was too small, it was combined with a neighbouring sub-village. Community sensitisation was conducted in advance of the survey to assist in maximising response rates. Within clusters, community leaders assisted with sampling, and identification of eligible individuals.One enumerator: medical studentTwo hearing testers: one audiometry nurse; one medical studentOne ear examiner: ENT specialist.Each team included:The IOV study revealed 100% agreement between results obtained on hearing tests across clinicians, using the most experienced audiology nurse as a gold standard. For ear examination the agreement was 85.7% in both the left and rights ears.All analysis was conducted in Stata 15.0 .Feasibility of a cluster size of 30 was examined by assessing the response rate, proportion of clusters completed in 1 day, number of survey days, and missing data.The time taken to complete the hearing test was recorded within the hearTest application. To assess the reliability of hearTest, three factors were considered: 1) 1 kHz test-retest reliability (1 kHz assessed twice in each ear); 2) false response rate (measured in hearTest); 3) ambient noise levels compared to the headphone maximum permissible ambient noise levels (MPANLs).Shapiro-Wilk tests were conducted to assess normality of time, and false response data. Based on evidence of non-normally distributed data, medians and interquartile ranges (IQR) were obtained to summarise time data.To account for clustering survey design the “svy” command was employed. To account for non-response according to age and sex, weighting was applied to the prevalence estimates to ensure they were representative of the population. This was conducted using the 2010 census data age and sex demographics of Jiangxi province, with five-year age stratum. Strata were compared to the observed population distribution in the sample, and weights calculated in the following manner:weight of stratum x = /.The derived weights were applied to estimate prevalence of hearing loss and ear disease. 95% confidence intervals (CI) were obtained around all estimates. Prevalence estimates were disaggregated by age and sex. The probable causes of any level of hearing loss were determined in each ear, and grouped by probable type. Consistency in the assignment of type was checked. For example, if impacted wax was assigned as the cause, but the degree of hearing loss was severe or greater, then the type was reassigned as mixed. The need for services was calculated based on Table Of 1421 eligible participants, 1344 people were examined (94.6%), 38 were not available (2.7%) and 39 refused (2.7%). The survey took 4.5 weeks (24 days) to complete with four teams. All 47 clusters were completed by one team in 1 day. The response rate for the survey was very high (94.6%). Of 1344 participants, 1342 completed the hearing test – with two missing tests due to illnesses (e.g. dementia). There were no other missing examinations or questionnaires. The median duration of the hearing test was 7.7 min . Reliability of testing was high with over 90% of test-retests at 1000 Hz within +/− 5 dB in both ears. Nearly all of tests had a false response rate of 10% or less (85.7%). The median false response rate was 4%. Ambient noise did not appear to impact testing in this study, the vast majority of tests were conducted in areas where ambient noise did not exceed the MPANLs see .Compared with census data, there was an underrepresentation of men, particularly in the younger age groups Table . A more The prevalence of moderate or greater hearing loss in the 50+ population of Gao’an was 16.3%  and for any level of hearing loss 53.2%   in the left and 6.0%  in the right. Overall, 6.0%  of ears had ear disease. The most common type of ear disease was impacted wax ; right 2.0% . The majority of participants had a normal ear examination ; right 93.7%   was acquired sensorineural hearing loss  followed by COM (dry perforation)  and impacted wax  . Extrapolated to the total population of Gao’an, this represents 108,000 people aged 50+. Wax removal services were required for 3.4% of the population (7000 people). Surgical assessments were required for 4.8% (9500 people). Medication was required for 2.0% of the population (4000 people). Table .Table 6n = 1) reported that they “seldom” wore them, the remaining two reporting that they always wore them. Reasons for this included “too much trouble to wear”, and “sound too loud”. Of those with hearing loss in either ear and/or ear disease in either ear, only 5.3% had previously sought care. Of these, 83.6% sought care at the public hospital, and 80% received medication. The vast majority of people (97.8%) who had not sought care who had hearing loss or ear disease said that they did not feel the need to go for services.Of those in potential need of hearing aids, only three reported that they had hearing aids (0.4% coverage). Four additional people also reported wearing hearing aids who were in need of surgical services for COM. Of those in need who owned hearing aids, a third , followed by diabetes (8.6%) and smoking  Table . Other rThis study describes the development and field-testing of the RAHL methodology for assessing the prevalence of hearing loss in population-based surveys in Gao’an, Jiangxi, China. The survey methodology focuses on people aged 50+ based on evidence from previous surveys that the majority of hearing loss is experienced by this age group . Mobile-The survey took 4.5 weeks (24 days) to complete with four teams, for a sample size of 1344. In comparison to an all-age survey conducted in 2005–2006, which took 20 months to complete four provinces, and the 60+ survey in 2014–2015 which took 13 months, this is rapid and therefore likely far lower cost , 43. We Considering the assessment protocol, using smartphone-based automated audiometry (hearTest) was well-accepted by participants. Using hearTest facilitated house to house sampling, without the need for a power source. The over the ear headphones used with hearTest as well as testing inside participant homes assisted with reducing background noise, which was not a significant problem in this survey. Only two people could not be tested, both due to other health conditions. Test took approximately 7 min per person, and reliability was high. In further planned field tests of the RAHL protocol, the exact time for each component of the survey will be measured to allow more detailed planning.The prevalence of moderate or greater and any level of hearing loss were estimated to be 16.3%  and 53.2%  respectively. There was no difference in prevalence by sex, but prevalence increased with age. The prevalence decreased with severity of hearing loss from 36.9%  mild, to 0.6%  profound. Overall, 6.0%  of ears had ear disease.In both the left and right ear, the main probable cause was acquired sensorineural hearing loss . Age, sex, and malaria were associated with increased risk of hearing loss. Literacy, used as a proxy measure for higher SEP, had a protective effect. Females had a decreased risk of hearing loss compared to males.Compared to previous studies, in 2005–2006, an all-age prevalence study was conducted in Jiangsu, Sichuan, Guizhou and Jilin provinces in China and found an all-age prevalence of moderate or greater hearing loss of 4.4% and a prevalence of 54.5% in people aged 50 + . These fThis survey provides useful information for planning services in Gao’an and provides a baseline for future studies in the county. In terms of service needs, over half of people needed diagnostic audiology and possible hearing aid fitting (54.0%). A smaller proportion needed wax removal (3.4%), surgical review (4.8%), or medication (2.0%). Only 0.4% of those in need had hearing aids. Very few people had previously sought care, the vast majority reported they did not feel the need. This may be due to lack of awareness about hearing loss and available treatments. At present, hearing aid fittings in the public system in Gao’an are provided only through hospitals in Nanchang. This study provides evidence that hearing aid services should be scaled up in Gao’an county and awareness raised. The prevalence of self-reported hypertension, smoking and diabetes were high – suggesting that primary and secondary prevention strategies are required for these conditions.There are some components of the RAHL methodology that need further attention. The analysis has reinforced some of the known challenges with collecting detailed information about the causes of hearing loss , 25, 45.However, inconsistencies in cause assignment were identified. For example, when a participant had severe or profound loss and the cause was assigned as impacted wax. In this situation, the cause is unlikely to be impacted wax alone – an underlying sensorineural component likely exists in addition. These causes were recoded as mixed in the analysis . The future intention with RAHL is to develop an automated analysis platform, and these types of inconsistencies may create barriers to this process. To improve consistency in cause assignment, further decision support within the mobile questionnaire will be developed for future surveys.Further guidance is needed on how to assign the probable cause when there are two causes in the same ear. The RAAB survey takes the approach of assigning the cause that is most amenable to treatment . This coTo help overcome some of the challenges with cause assignment, risk factor analysis was conducted. This analysis found that only age, sex, malaria and literacy were associated with hearing loss. The utility of including an analysis of association with known risk factors in a survey report intended for planning is not clear. Recall bias and lack of health awareness may affect the responses. The specific questions used to ascertain data on risk factors should be reviewed in light of these findings. This analysis should be replicated in other settings before determining its value.In future research, we will examine whether the addition of tympanometry may help with assigning the type, and reduce the proportion of unknown causes. Tympanometry may be useful in the diagnosis of OME, which can be more difficult to determine from otoscopy alone .This survey has several strengths. A rigorous two-stage sampling procedure was used to select participants. The response rate was very high. Validated smartphone tools were used, for the first time in a population-based survey of hearing loss.There are also some limitations with the study that should be taken in to account. Measuring SEP is important for understanding health equity. Previous work has recognised the difficulties in differentiating SEP based on assets in upper middle-income countries such as China, where the majority of households own key domestic goods . For thiThe RAHL survey methodology was developed to measure the prevalence and probable causes of hearing loss in population-based surveys in a low cost and rapid manner. Specifically, it aims to overcome the financial and logistical barriers of previous all-age surveys of hearing loss allowing data to be obtained quickly and utilised in district level planning. Field-testing of the RAHL survey in China confirmed that the protocol is feasible, and substantially faster than an all-age survey. The prevalence of moderate or greater hearing loss in the 50+ was high, increases with age, and decreases with degree. The prevalence found was also comparable to previous surveys conducted in China. The vast majority of people in the survey had hearing loss that was probable sensorineural or mixed in nature, and have the potential to benefit from hearing aids. Information gathered from this survey can be used to plan and advocate for improved ear and hearing care services at the county-level in Gao’an. Aspects of the survey that need further development include how causes could be better assigned, and how data should be reported in for planning purposes.


Introduction: Disabling hearing loss as a sequela of bacterial meningitis results from damage to the auditory system. This study was designed to ascertain the hearing thresholds in survivors of bacterial meningitis and the risk factors of hearing loss in childhood bacterial meningitis.Methodology: One hundred and two children admitted and treated for bacterial meningitis were recruited prospectively along with 102 age- and sex-matched controls who had auditory evaluation using otoacoustic emission and auditory brain stem response tests 48 h prior to hospital discharge. This was also repeated at the follow-up clinic at 1 month after hospital discharge, irrespective of the initial hearing assessment results.Result: There were 57 (55.9%) males and 45 (44.1%) females among the cases  and 55 (53.9%) males and 47 (46.1%) females among the controls . The prevalence of hearing loss was 30.4% among the cases, while it was 6.9% among the controls. The risk factors of hearing impairment in this study were the presence of anemia, leukocytosis, and hypoglycorrhachia.Conclusion: Hearing impairment with varying degrees of severity is a frequent complication of bacterial meningitis in children. Bacterial meningitis is the inflammation of the brain meninges  due to bacterial infection . It is aHaemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitides. S. pneumoniae has the highest fatality and is more frequently associated with disabilities, followed by H. influenzae type b and N. meningitides , and children that met the inclusion criteria were recruited consecutively, after obtaining consent from the caregivers. Children aged between 2 months and 14 years were recruited into the study after confirmation of a diagnosis of bacterial meningitis by a pediatric neurologist as defined by the World Health Organization (WHO) guidelines based on symptoms, signs, and laboratory findings  test was done using a Labat hand-held OAE machine , followed by a diagnostic auditory brain stem response (ABR) test using an MB II classic device . This auditory evaluation was also done for the controls. Each ear was assessed separately, based on the recommendation of the American Academy of Audiology . The estThere were 102 cases of bacterial meningitis: 57 males and 45 females, with a male-to-female ratio of 1.2:1. The control group was made up of 55 males and 47 females. The age of both the cases and the controls ranged from 2 months to 14 years, with a median age of 4 years among the cases, while among the control subjects the median age was 5.9 years. The age distribution of the study subjects and the socioeconomic class distribution are shown in p = 0.04).p = 0.01). Abnormal ABR-estimated thresholds were seen in 55 ears among the cases , giving a prevalence of 30.4%. Among the controls, 11 ears had abnormal ABR thresholds , giving a prevalence of 6.9%. There was a statistically significant difference in the prevalence of hearing loss between the cases and the controls (OR = 1.554), abnormal packed cell volume (OR = 0.933), white blood cell count (OR = 1.080), and random blood sugar (RBS)/cerebrospinal fluid (CSF) sugar ratio  is diagnosed in the presence of a normal OAE response with an abnormal ABR threshold , 24, whiFluctuations in the sensorineural hearing loss following bacterial meningitis in children have been reported in the literature , 16. SomS. pneumoniae as the infective organism; (7) nuchal rigidity  illness >24 h before intervention ; (2) sevrigidity ; (8) seirigidity ; (10) agrigidity . The widThe main limitation of this study is the lack of premorbid hearing thresholds of the children studied. Hearing impairment is a frequent complication of bacterial meningitis, and the probable site of lesion is the cochlea and/or the auditory nerve. The factors that worsen hearing loss in children with bacterial meningitis are anemia, leukocytosis, hypoglycorrhachia, and duration of illness before appropriate medical intervention.All datasets generated for this study are included in the article/supplementary material.The studies involving human participants were reviewed and approved by University of Ibadan, University College Hospital Ibadan Ethics Committee. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.MJ, AA, IL, and ON contributed to conception and designed the study. MJ, AA, and SO drafted the manuscript. All the authors contributed to manuscript revision and approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Achieving an ideal morphology is an imperative avenue for enhancing key parameters toward high‐performing organic solar cells (OSCs). Among a myriad of morphological‐control methods, the strategy of incorporating a third component with structural similarity and crystallinity difference to construct ternary OSCs has emerged as an effective approach to regulate morphology. A nematic liquid‐crystalline benzodithiophene terthiophene rhodamine (BTR) molecule, which possesses the same alkylthio‐thienyl‐substituted benzo moiety but obviously stronger crystallinity compared to classical medium‐bandgap polymeric donor PM6, is employed as a third component to construct ternary OSCs based on a PM6:BTR:Y6 system. The doping of BTR (5 wt%) is found to be enough to improve the OSC morphology—significantly enhancing the crystallinity of the photoactive layer while slightly reducing the donor/acceptor phase separation scale simultaneously. Rarely is such a morphology evolution reported. It positively affects the electronic properties of the device—prolongs the carrier lifetime, shortens the photocurrent decay time, facilitates exciton dissociation, charge transport, and collection, and ultimately boosts the power conversion efficiency from 15.7% to 16.6%. This result demonstrates that the successful synergy of liquid‐crystalline small‐molecule and polymeric donors delicately adjusts the active‐layer morphology and refines device performance, which brings vibrancy to the OSC research field. The nematic liquid‐crystalline small‐molecule donor benzodithiophene terthiophene rhodamine (BTR) works as a successful third component in PM6:Y6‐based organic solar cells. The doping of BTR significantly enhances the crystallinity with slightly reducing donor/acceptor phase separation of the photoactive layer. This uncommon morphology evolution facilitates charge separation, transport, and collection and ultimately boosts the efficiency from 15.7% to 16.6%. The last decade has witnessed the vitality of the OSC research field, which is brought by the concerted effort of materials engineering, device optimization, and device physics.Organic solar cells (OSCs) are rising as a potential rival for delivering both high power conversion efficiencies (PCEs) and low large‐scale manufacturing costs, compared with the traditional silicon devices.7, 8 Disappointingly, the research on morphological control is usually scattered and even fragmentary, and some working mechanisms are still unclear. Morphology in OSC is complicated and is almost always regulated by trial and error. Moreover, these conventional techniques always inevitably enlarge domain size excessively and sacrifice charge separation when crystallinity is evidently strengthened, which throws the morphological control work into a dilemma. To our best knowledge, very few works have reported the coexistence of obviously stronger crystallinity and reduced phase separation via device engineering.As organic semiconductors typically present low dielectric constant and short exciton diffusion length, the control of donor/acceptor (D/A) blend morphology, which is the integrated result of the nature of donors and acceptors , the film processing, and the device configuration, is crucial for achieving efficient charge separation, transport, and collection. A number of device‐engineering methods have been employed to regulate morphology, such as optimizing D/A ratio, opting solvents and additives, thermal annealing, solvent annealing, and post solvent treatment.39 Dis The third component usually exerts one or multi functions of broadening/strengthening the absorption spectra, facilitating charge transfer/transport/collection, reducing carrier recombination, and optimizing the active‐layer morphology. Despite the aforementioned challenges of achieving ideal morphology, the success of utilizing the third component of a similar structure with the host materials represents a key concept to regulate morphology. Early in 2015, by comparing successful and failed multiple‐donor systems, Yang and co‐workers found that the harmonious coexistence of two structural compatible polymeric donors (PTB7 and PBDTT‐SeDPP) endowed the PTB7:PBDTT‐SeDPP:PC71BM OSCs with a high PCE of 8.7%. Also, the cooperation of ITCPTC and MeIC, two structure‐similar and absorption‐similar small‐molecule acceptors helps fine‐tune the crystallinity and phase separation of the PM6:ITCPIC:MeIC blend. Besides, the crystallinity of the involved active‐layer materials is considered as another vital parameter to control morphology. The polymeric donor (Si‐PCPDTBT) of strong crystallinity demonstrates a good example. A set of Si‐PCPDTBT‐based ternary OSCs using P3HT:PC61BM, P3HT:ICBA, and PTB7: PC71BM host systems have been reported, where the introduction of Si‐PCPDTBT facilitates charge transport, suppresses charge recombination, and elevates PCE. The concepts of structure similarity and crystallinity difference are combined in the recent all‐small‐molecule work of our group, where the incorporation of a dehydroxylated derivative of benzodithiophene terthiophene rhodamine (BTR), namely, BTR‐OH into the BTR:PC71BM system affords a champion PCE of 10.14% at a substantial blend thickness of 300 nm. It is because the less crystalline BTR‐OH weakened the crystallinity of the donor phase and optimized the D/A phase separation to a suitable scale, and thereby balanced the hole and electron transport. In spite of the effectiveness of structure‐similar but crystallinity‐different strategy, the application scope needs further extension.Ternary OSCs have become an important research branch of device engineering, on account of their validity in overcoming the weaknesses of binary‐blend OSCs and retaining the simplicity of single‐junction OSCs.48 The On the one hand, PM6 and BTR both comprise alkylthio‐thienyl‐substituted benzo building block, which presumably guarantees their good compatibility. On the other hand, the nematic liquid‐crystalline BTR has obviously stronger crystallinity than PM6. Last year, Zou group designed and synthesized a nonfullerene acceptor Y6, which features a ladder‐type electron‐deficient core‐based central fused ring (di‐thienothiophen[3.2‐b]‐pyrrolobenzothiadiazole) with a benzothiadiazole (BT) core. Outstanding PCEs of 15–16% are achieved by using wide bandgap polymer donors like PM6. The broad and high photoresponse was recorded at a high open‐circuit voltage, implying energy loss was as low as ≈0.5–0.6 eV. This superior performance of Y6 makes itself widely used in recent research work. Encouraged by the strategy of structure similarity and crystallinity difference, we incorporate BTR into the PM6:Y6 binary blend to further refine morphology and efficiency. It is worth mentioning that the doping of BTR (5 wt%) evidently enhances the crystallinity of the photoactive layer and slightly weakens the phase separation simultaneously, which is rarely reported in the literature. This morphology evolvement is associated with prolonged carrier lifetime, shortened photocurrent decay time, improved charge separation, transport, and collection, which ultimately boosts the PCE from 15.7% to 16.6%. This work elucidates the delicate effect of morphology tuning with the collaboration of liquid‐crystalline small‐molecule and polymeric donors and improves the OSC device performance.BTR is a high‐performing small‐molecule donor material with excellent optoelectronic properties and nematic liquid crystal behavior. Hence, BTR presents strong intermolecular interaction, which is beneficial for maintaining a long‐range directional order and possessing high hole mobility.61 On Scheme Figure Table J–V) characteristics of optimized binary and ternary OSCs based on PM6:Y6, PM6:BTR:Y6, BTR:Y6 in different weight ratios. These OSCs are fabricated using the same process parameters for direct comparison. Binary device based on BTR:Y6 shows extremely low fill factor (FF) of 32.8% and PCE of 4.00%, with a short‐circuit current density (JSC) of 15.7 mA cm−2 and an open‐circuit voltage (VOC) of 0.776 V. In contrast, the PM6:Y6 blend exhibits a PCE of 15.7%, along with a VOC of 0.840 V, a JSC of 25.1 mA cm−2, and an FF of 74.4%, which is in accord with the literature. After adding 5 wt% loading of BTR into PM6:Y6 system, JSC is effectively improved to 25.8 mA cm−2 and FF is obviously increased to 76.7%, which cover the negligible reduction of VOC from 0.840 to 0.839 V and successfully elevate the efficiency to 16.6%. According to the external quantum efficiency (EQE) spectra, the respective integrated JSC’S of devices based on PM6:Y6, PM6:BTR:Y6, and BTR:Y6 blends are 24.5, 25.2, and 14.8 mA cm−2, which agree well with the JSC value from the J–V curve  as a function of the effective voltage (Veff) . This means the introduction of BTR has a negligible contribution to absorption. The exciton dissociation efficiency (ηdiss) and charge collection efficiency (ηcoll) are calculated quantitatively, according to the equations of ηdiss = JSC/Jsat and ηcoll = Jmax/Jsat, respectively. The BTR:Y6 device displays extremely low ηdiss of 63.6% and ηcoll of 30.8%, which accounts for its disappointing performance. By contrast, the PM6:Y6 device reveals a ηdiss of 93.9% and a ηcoll of 83.8%, and the doping of BTR into PM6:Y6 blend availably improves ηdiss and ηcoll to 96.8% and 87.7%, indicative of the most efficient exciton dissociation and charge collection in the ternary blend.To decipher the role of BTR in the PM6:BTR:Y6 ternary blend, charge separation and extraction properties are further studied by plotting the photocurrent density (τ) of the open‐circuit conditions are extracted from the TPV decay dynamics under the irradiation of a simulated 1 sun using mono‐exponential fits. The ternary device displays a τ value of 1.62 µs, obviously larger than their parallels incorporating PM6:Y6 (1.40 µs) and BTR:Y6 (1.27 µs) blends, which unveils that charge recombination intensifies from PM6:BTR:Y6, PM6:Y6, to BTR:Y6 in order. TPC can probe the competition between carrier sweep‐out and recombination processes during OSC operation. The photocurrent decay time of the PM6:BTR:Y6 device under the short‐circuit condition is 0.75 µs, visibly shorter than that of the PM6:Y6 device (0.84 µs) and BTR:Y6 device (0.94 µs). It manifests that the combination of BTR and PM6 effectively facilitates charge extraction and accounts for the aforementioned highest charge collection efficiency of 87.7% for the ternary device.In‐depth understanding of the charge recombination and extraction dynamics is attained from transient photovoltage (TPV) and transient photocurrent (TPC) measurements Figure ,f. The cμe) of 2.96 × 10−4 and 2.05 × 10−4 cm2 V−1 s−1, which are far surpassed by the ternary‐blend rival with a μe of 3.59 × 10−4 cm2 V−1 s−1. The hole mobilities (μh) are derived from hole‐only devices involving the ITO/MoOx/active layers/MoOx/Al structure. The BTR:Y6 blend exhibits a μh of 7.61 × 10−4 cm2 V−1 s−1, evidently higher than the PM6:Y6 parallel (4.77 × 10−4 cm2 V−1 s−1). The addition of BTR into PM6:Y6 blend effectively improves the μh to 5.53 × 10−4 cm2 V−1 s−1. The ratios of μh and μe are calculated to be 1.61, 1.51, and 3.71 in PM6:Y6, PM6:BTR:Y6, and BTR:Y6 blends, respectively. The highest and most balanced charge mobilities of PM6:BTR:Y6 blends account for its weakest charge recombination ascertained by TPV and its highest FF of 76.7%. By comparison, the extremely unbalanced mobilities of BTR:Y6 blends explain the strong charge recombination and the disappointing FF of 32.8% therein.The charge mobilities are fitted from the dark current density–voltage curves using the space‐charge‐limited current model . Electron‐only devices are constructed with the architecture of ITO/ZnO/active layer/PFNBr/Al. The PM6:Y6 and BTR:Y6 blends display electron mobilities , (200), and (300) lamellar peaks at qr ≈ 0.34, 0.66, 0.99 Å−1 along the in‐plane (ip) direction, and the (100) peak of BTR presents a large crystal coherence length (CCL) of 232.5 Å. The third‐order diffraction and the large CCL together evidence BTR's strong crystallinity. The PM6 neat film exhibits lamellar peaks and π–π peaks at qz ≈ 0.295 and 1.70 Å−1 along the out‐of‐plane (oop) direction and thus demonstrates more amorphous nature than BTR. The NFA Y6 exhibits face‐on packing by displaying the oop π–π peaks at qz ≈ 1.77 Å−1 and ip lamellar peaks at qr ≈ 0.286 Å−1. As for the blend films, BTR:Y6 blend displays preferential edge‐on packing, which is unfavorable for charge transport toward electrodes. The PM6:Y6 and PM6:BTR:Y6 counterparts exhibit preferential face‐on packing by possessing oop (010) peaks at qz ≈ 1.75 Å−1 (d ≈ 3.60 Å) and ip (100) peaks at qr ≈ 0.30 Å−1 (d ≈ 20.9 Å). To carefully compare the crystallinity of blend films with and without BTR, the CCL and integrated area of (100) and (010) peaks are fitted. The PM6:BTR:Y6 blend displays respective CCLs of 97.8 and 22.9 Å for (100) and (010) peaks, slightly smaller than PM6:Y6 counterpart (98.5 and 24.1 Å). Despite the similarity of CCL, the ternary blend displays respective areas of 168.11 and 497.81(a. u.) for (100) and (010) peaks, more than twice as much as those of PM6:Y6 parallel (76.62 for (100) and 221.37 for (010)). Scheme μh and μe, as well as the reduced charge recombination, in accordance with the TPV results.Grazing‐incidence X‐ray diffraction (GIXD) is employed to study the crystalline structure of neat and blend films. The 2D diffraction patterns and 1D line‐cuts are depicted in Figure Another important parameter of blend morphology, the donor/acceptor phase separation, is studied by atomic force microscopy (AFM) and transmission electron microscopy (TEM). As the AFM height images show . Such a strategy manifests the successful synergy of liquid‐crystalline small‐molecule donor and polymeric donor, which provides an alternative guideline to further fine‐tune the morphology toward new breakthroughs in OSCs.In summary, we successfully designed an interesting ternary OSC based on harmonious coexistence of structural compatible nematic liquid‐crystalline small‐molecule donor (BTR) and polymeric donor (PM6) paired with NFA (Y6) that delivered a champion PCE of 16.6%, exceeding the PM6:Y6 and BTR:Y6 binary devices (15.7% and 4.0%). The role of BTR as a third component is systematically deciphered. We observed the simultaneous improvement of The authors declare no conflict of interest.Supporting InformationClick here for additional data file.


The use of neonatal hearing screening has enabled the identification of congenital unilateral sensorineural hearing loss (USNHL) immediately after birth, and today there are several intervention options available to minimize potential adverse effects of this disease, including cochlear implantation. This study aims to analyze the characteristics of the inner ear of a homogeneous group of congenital non-syndromic USNHL to highlight the features of the inner ear, which can help in clinical, surgical, and rehabilitative decision-making. A retrospective chart review was carried out at a tertiary referral center. Systematic diagnostic work-up and rigorous inclusion–exclusion criteria were applied to 126 children with unilateral hearing impairment, leading to a selection of 39 strictly congenital and non-syndromic USNHL cases, undergoing computed tomography (CT) and magnetic resonance (MR) imaging studies. The frequency and type of malformations of the inner ear in USNHL and unaffected contralateral ears were assessed, with an in-depth analysis of the deficiency of the cochlear nerve (CND), the internal auditory canal (IAC) and the cochlear aperture (CA). Inner ear anomalies were found in 18 out of 39 (46%) of the USNHL patients. In 1 subject, the anomalies were bilateral, and the CND resulted in the predominant identified defect , frequently associated with CA stenosis. Only 3 out of 14 children with CND presented stenosis of the IAC. CND and CA stenosis (and to a much lesser extent IAC stenosis) are a frequent association within congenital and non-syndromic USNHL that could represent a distinct pathological entity affecting otherwise healthy infants. In the context of a diagnostic work-up, the evaluation with CT and MRI measurements should take place in a shared decision-making setting with thorough counseling. Both imaging techniques have proven useful in differentiating the cases that will most likely benefit from the cochlear implant, from those with potentially poor implant performance. Interest in the management of childhood unilateral sensorineural hearing loss (USNHL) has significantly increased in recent years. The reasons stem primarily from the growing awareness that functional binaural hearing requires sound input for both ears2. Furthermore, thanks to the widely adopted universal newborn hearing screening programs, the diagnosis of congenital USNHL can now be made in the first few months of life instead of being detected in preschool and school-age4, allowing early treatment. However, another incentive for USNHL treatment arises from the technological advancements of hearing devices6.Estimates of the universal newborn hearing screening programs suggest that around 1–2 in 1000 infants have significant hearing loss, with a unilateral deficit representing one-third of all the children born with permanent hearing loss7. Adults with USNHL experience difficulties in localizing sounds and understanding speech, competing with environmental noise8. If the USNHL is congenital or occurs in the first years of life, the localization skills seem to be less compromised, possibly due to the successful use of monoaural cues through developmental compensation9. However, many papers highlighted the negative consequences of USNHL on children’s development, which include delayed or impaired auditory skills10, increased risk of receptive and expressive language problems11, behavioral and educational challenges12, and reduced hearing-related quality of life13. The etiology of congenital USNHL is much less defined than bilateral sensorineural hearing loss, and although specific causative agents are not often recognized15, the literature indicates a high frequency of inner ear malformations in congenital USNHL cases18. Temporal bone anomalies are identified in 29–40% of pediatric USNHL when assessed by CT. In 10–25% of the cases, MR detects anomalies of the cochlear, vestibular, or facial nerves, of the cerebellopontine angle structures, or auditory pathways19. It is essential to recognize an inner ear malformation to clarify the underlying pathology, to offer critical information in terms of possible hearing loss progression or contralateral involvement, as well as to provide tips for counseling and treatment. Indeed, rehabilitation management has been variably provided to children with USNHL, with a range of options available but, so far, no evidence of the superiority of one approach to another20. In the past, the most conventional approach to congenital USNHL was watchful waiting and monitoring of auditory-language development21. There are now several devices available for USNHL prosthetic treatment: acoustic hearing aids, contralateral routing of signal hearing aids, bone conduction hearing implants and cochlear implants22. Cochlear implant has recently sparked increasing interest as a treatment option24, described as the most likely tool for improving binaural hearing for adults and children affected by severe-to-profound USNHL25. A systematic review established that no firm conclusions can be drawn on the efficacy of cochlear implant in children with USNHL, due to the heterogeneous findings and small sample sizes26. The significant variability of the outcomes can be attributed to heterogeneous etiologies and times of the onset of USNHL .Gordon and Papsin (2019) described the binaural hearing as a function that provides a map of our environment in all the directions, which we use to separate and group auditory streamsCharacteristics of inner ear malformations on the affected side;Anomalies on the contralateral unaffected side;Cochlear nerve deficiency (CND), cochlear aperture (CA) stenosis and internal auditory canal (IAC) stenosis.This study aims to analyze the characteristics of the inner ear of a homogeneous group of congenital non-syndromic USNHL in order to highlight the anatomical features that can help in clinical, surgical, and rehabilitative decision-making. We focused on:This retrospective chart review involves all children who have been diagnosed with a permanent USNHL and assessed using imaging techniques from 2012 to 2019 at the Department of Otorhinolaryngology and Audiology of the Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, Italy. USNHL was defined as bone conduction pure tone threshold average of 500, 1000 and 2000 Hz, > 40 dB hearing level (HL) in the affected ear and < 15 dB HL in the contralateral unaffected ear. Hearing loss degree was classified as moderate (41–60 dB HL), severe (61–80 dB HL) or profound (> 80 dB HL). The identified children (n = 126) underwent a systematic diagnostic work-up, which included ear, nose and throat examination, ophthalmologic evaluation, kidney ultrasonography, electrocardiogram, and inner ear imaging, mainly aimed at verifying the presence of syndromes or inner ear malformations. Cytomegalovirus infection was ruled out after the failure of the universal newborn hearing screening. In the case of older infants with late USNHL diagnostic work-up, a detailed brain MR review was performed, to highlight abnormalities possibly involved with a congenital cytomegalovirus infection syndrome. Audiological tests confirmed a hearing loss and classified its type, laterality and degree. In order to gather a homogeneous population of congenital USNHL, strict inclusion and exclusion criteria have been applied  who met the inclusion and exclusion criteria, as reported in Table Both temporal bone CT and cerebral MR were performed in the same session during natural sleep or sedation, if necessary. Temporal bone CT: patients were examined by high-resolution CT Philips Brilliance 40, with a slice thickness of 0.67 mm, slice increment of 0.33 mm, collimation 16 × 0.625 mm, time of rotation 1 s., amperage 140 kV, mAs 400mAs, CTDI 93.7 mGy, DLP mGy*cm 503.16, the scale of the length of 52.8 mm and field of view of 155 mm. Temporal bone MR: patients were examined with Philips Ingenia 1.5 T with DRIVE 3D HR sequences: TE 198 ms; TR 1500 ms; ETL 40; the field of view of 160 mm; isotropic voxel of 0.6 × 0.6 × 0.6 mm, interpolate 50%; matr. 252 × 265; scan percentage 80%; slice thickness 0.9 mm.28. The average range values were directly selected from the previously published literature for other parameters such as the cochlear aperture, vestibular aqueduct, cochlear length, cochlear nerve32. Precisely, this study was based on the following parameters and standard range measurement:31 who provided a cut off elaborated with an explicit methodology;The cochlear aperture (CA) was measured in its mid-portion at a mid-modiolar level and was classified as “normal”, “aplastic” (when completely ossified) or “stenotic” (≤ 1.2 mm), based on Lim et al.28;The cochlear basal turn was measured from the bone cochlea near the oval window to the furthest end of the basal turn 28;The cochlear middle turn was measured in its largest part 30 28;The cochlear height was measured from the base of the modiolus, through the modiolus, to the cochlear apex32. It has been defined “enlarged” if greater than 2 mm;The vestibular aqueduct was measured at the midpoint between the common crus and the operculum28;The bony island width of the posterior semicircular canal was measured in axial view at its greatest diameter 28;The bony island width of the lateral semicircular canal was measured in coronal view at its greatest diameter 28;The bony island width of the superior semicircular canal was measured in coronal view at its greatest diameter 30;The cochlear length was measured from the medial point of the round window (air-perilymph interface) to the more external bony point, passing through the modiolus (range: 8.1–9.59 mm)28.The coronal width of the internal auditory canal (IAC) was drawn perpendicular to an imaginary line from the transverse crest to the mid-point of the porus. MR measurements:29 and contralateral cochlear nerve diameter. The terms of aplasia and hypoplasia are also referred as cochlear nerve deficiency (CND);The cochlear nerve was evaluated on axial and especially on sagittal-oblique images. It was classified as “aplastic,” “hypoplastic,” or “normal” according to its size compared to the ipsilateral facial nerveThe endolymphatic sac was defined as “not visible” or “visible,” although not included in the statistical comparison.A dedicated pediatric radiologist, a temporal bone imaging expert, with no information on the affected child's ear, examined and compared the imaging.The measurements were reconstructed on axial, coronal, and oblique-sagittal views using the Picture Archiving and Communication System. The measures were reported in millimeters; dimensions from 1 to 6 were measured on axial, while 8–10 on the coronal plane. The standard range values for the basal and middle turn of the cochlea, the cochlear height, the bone island width of the semicircular canals, and the coronal width of the internal auditory canal were calculated based on the average measurement of our normal controls minus/plus 2 standard deviations-SD33.Inner ear malformations were documented according to Sennaroğlu Classification34.We evaluated 14 children (23 ears) not affected by sensorineural hearing loss who performed audiometry, CT and MR for other reasons, mainly of chronic ear surgery. In the case of cholesteatoma history, the affected ear was ruled out for the possible presence of cochleovestibular anomalies in this type of pathologyp < 0.05), we decided to obtain a statistical indication using a nonparametric test. We described variables with medians and quartiles. Comparisons between groups were made using Wilcoxon rank-sum test for continuous variables, and Fisher’s exact test for categorical variables. P values < 0.05 were considered significant. Data were analyzed and visualized using Excel (version 16.23) and R Commander (version 3.6.0 GUI 1.70)35.Given the small group of subjects and the non-normal distribution of the data samples .Informed consent was obtained from a parent and/or legal guardian of all participants included in the study.Table p = 0.001), and in only 3 CNDs a stenotic IAC was found. The 4 CNDs without CA stenosis were associated with an EVA in 2 cases, with an IP2 in 1 case, while the last CND case (cochlear nerve aplasia) presented only with an isolated stenotic IAC.The CND, classified as hypoplasia (n = 7) or aplasia (n = 7), was the more represented pathological picture (35.9%). All aplasia cases showed a profound hearing loss, while hypoplasia was associated with a variable degree of hearing loss. Two CNDs were found in the right ear, while the other 12 CND cases belonged to left ears. In 10 out of 14 USNHL cases, the CND was associated with CA stenosis . In 4 out of 6 EVAs, the endolymphatic sac was visible on MR images. In 1 case, it was possible to visualize the endolymphatic sac without the appreciation of a vestibular aqueduct diameter > 2 mm.The anomalies of the bony island of the lateral semicircular canal (SCC) did not appear to be related explicitly to USNHL: we detected reduced bony island dimensions in 3 unaffected ears and 2 USNHL sides. Only in one subject of our series, the lateral SCC bony island anomaly was bilateral: the USNHL side harbored the IP 1 malformation with lack of lateral SCC bony island, and the contralateral normal hearing side presented a lateral SCC bony island < 2.4 mm.W = 438.5, p < 0.01) and normal controls . Overall, also cochlear height measurements were bilaterally smaller in USNHL children, even though only 3 out of 39 in the affected side and 4 in the unaffected side subjects resulted below our normal range values.  of our population, most frequently associated with CA stenosis. Both of these anomalies have been previously reported in the literature, although more often individually, or described as a possible feature within more heterogeneous populations38.Our study confirms that individuals with congenital USNHL are more likely to have inner ear malformations than those with congenital bilateral hearing loss41, we adopted strict exclusion and inclusion criteria to focus on a strictly selected population. Besides, only a few reports have analyzed USNHL functionality with a double imaging technique (CT and MRI) on a significant number of patients with non-syndromic congenital USNHL. A multi-institutional retrospective imaging study review was conducted by Shah et al.39 on 219 patients with USNHL aged 0–18 years that underwent CT and/or MRI. The overall prevalence of abnormal radiological findings associated with USNHL was 40%. EVA was the most common positive finding (15%) identified on CT imaging, while CND was the most common anomaly (52%) in 16 out of 31 patients who underwent MRI only. Similarly, to our description, there were many patients with more than one positive finding on imaging. This study did not include a measurement of the CA on CT images, and therefore it was not possible to relate CA stenosis and CND in these patients. By applying stricter inclusion criteria, Lim et al.31 analyzed the medical records and temporal bone CT scans of 42 patients under the age of 13 years with a diagnosis of USNHL with unknown etiology . A CA < 1.2 mm was detected in 52.4% of the total population. Even this study did not include MR images nor a normal control group. Vilchez-Madrigal et al.42 compared the CT imaging studies of 36 children with unilateral CA stenosis (< 1.0 mm), with controls without temporal bone injury. Contralateral ears had smaller CA (p < 0.00) and cochlea (p < 0.00) than controls, although to a lesser extent than on the stenotic side.Unlike most studies describing inner ear anomalies in USNHL patients37, the detection of IAC stenosis alone may be insufficient to indicate a CND: therefore, the CA is also required to predict cochlear nerve status. It is worth observing that there is no general agreement regarding how to measure the IAC width37, and the CA’s diameter can therefore represent a more reliable measure. Further morphological and genetic studies could, in the future, define whether the heterogeneity of the presence of the three anomalies described  belongs to a continuum of the pathology of the inner ear.Thanks to the comprehensive anatomical imaging study of the inner ear structures in a homogeneous population, our work has linked CA stenosis and CND as a specific and frequent pathological profile in congenital non-syndromic USNHL. Contrary to general clinical opinion, aplasia/hypoplasia is not systemically or frequently associated with IAC stenosis in congenital USNHL. Only 2 cases of aplasia out of 14 CND showed the co-presence of a stenotic CA and an IAC stenosis, and only in 1 case out of 14 CND the stenotic IAC was isolated. As indicated by Tahir et al.43 compared the post-cochlear implant speech performances among 3 groups of various CA diameters . CND occurred more frequently in the group with a diameter of < 1.4 mm which, also showed a worse post-cochlear implant outcome.The interest in CA is aroused by the fact that a narrow cochlear aperture probably indicates an anatomical or functional deficiency in the cochlear nerve. Consequently, a CA stenosis appeared to be a criterion for a negative outcome of the cochlear implant surgery, indicating that patients with stenotic CA demonstrate poorer cochlear implants results than patients with normal CA. Chung et al.The observations on the imaging of our work are relevant in today's perspective of the audiological management of congenital USNHL. Today's advantage in identification times and observations of our study stress the importance of adopting a very comprehensive diagnostic work-up in order to characterize the USNHL critical elements that can lead to the most rational and timely therapeutic approach.44. The main issue is exposure to CT radiations. We believe that a comprehensive imaging evaluation should take place in a shared decision-making setting with thorough counseling, taking into account that inner ear malformations are associated with congenital USNHL and an increased risk of developing bacterial meningitis in the pediatric population17. This was the case of one child in our series, who presented a cochleovestibular cystic malformation (IP-1), known to be associated with a higher risk of spontaneous cerebrospinal fluid fistula and recurrent meningitis33. An early temporal bone CT in the diagnosis of USNHL could be 17.4 to 80.3 times more likely to help prevent meningitis than to be associated with a subsequent malignant abnormality due to exposure to CT radiations18.The literature has discussed the need for early imaging in USNHL45; the second, aims to recover binaural hearing through traditional amplification or cochlear implantation. Contralateral routing of signal hearing aid, bone conduction hearing implants or cochlear implants are indicated for USNHL in the range of single-sided deafness with the abovementioned differential approach: contralateral routing of signal hearing aid and the bone conduction hearing implant deliver the stimuli to the normal hearing ear, while the only chance to restore a real binaural hearing in single side deafness is a cochlear implant. Bone conduction hearing implant can offer more advantages than contralateral routing of signal hearing aid amplification for USNHL46. However, there is still no compelling evidence that one of these strategies is superior to others in terms of hearing outcomes and cost-utility48. As regards the pediatric population, studies of cochlear implant results frequently include non-congenital USNHLs, i.e., children with some binaural hearing experience and short hearing deprivation27. Cochlear implants are still to be considered an emerging treatment option for children with congenital USNHL, and even the most recent literature reports only limited descriptions of the benefit of cochlear implant in these cases49. Therefore, evidence-based decisions regarding the most appropriate management in USNHL children are still lacking. In this perspective, our study shows that over a third of congenital and non-syndromic "idiopathic" USNHLs affecting otherwise healthy infants may not be suitable for current cochlear implant technology. In fact, among other factors known to influence cochlear implant outcomes, the choice (and benefits) of a cochlear implant depends on neuronal health and the presence of an inner ear malformation. Aplasia or hypoplasia of the auditory nerve is the primary concern, due to the possibility of compromising nerve stimulation through electrical impulses delivered by the cochlear implant. The literature reports that children with CND are generally considered poor candidates for cochlear implant surgery, and only a minority of children implanted with CND achieve good results50.Interventions in pediatric USNHL include surgical and non-surgical devices that can be divided into 2 broad categories: in one approach, the intent is to transmit auditory stimuli that come from the impaired side to the healthy ear51, it is only with the recent introduction of cytomegalovirus testing on urine samples of infants in their first weeks of life that is possible to exclude a congenital cytomegalovirus -related hearing loss52.The present study has some limitations. The retrospective nature of data collection makes it subject to possible bias. Despite the strict inclusion and exclusion criteria, it is sometimes difficult to ascertain the congenital origin of the USNHL. Only 11 of the 39 USNHL children investigated were detected through the UNHS program, which became mandatory in our region in 2012, and in Italy, in 2017. Similarly, although all children performed a brain MR whose analysis excluded subjects with signs of congenital cytomegalovirus infection syndrome53. The visibility of the nerve depends on the intensity of the magnetic field. The hypoplasia/aplasia ratio would increase if conducted using a device with higher magnetic field. Future prospective studies together with an accurate diagnostic work-up and strict imaging criteria will allow obtaining more details on the prevalence and clinical distinction of the different pathogenetic profiles in congenital USNHL. However, this study’s strength is to rely on a blind assessment of inner ear imaging performed by a dedicated radiologist who was aware of the clinical and audiological picture of the patients. Other authors have pointed out that the increase in clinical records using a multicentric collaboration, significantly increases the simultaneous risk of higher variability in imaging criteria and reports39.Another issue is the cochlear nerve measurements based on comparison with a neighboring nerve rather than a range of reference values of the nerve diameter. Furthermore, the non-visualization of cochlear nerve in MR does not necessarily imply the complete absence of nerve fibers due to the difficulty of detecting small nervesCongenital non-syndromic USNHL is frequently linked to inner ear malformations, which occurs, almost always, only on the affected side and is, in most cases, represented by CND combined with CA stenosis. CT and MRI are needed to identify specific abnormalities that could shed light on the pathogenesis of congenital USNHL, affecting the therapeutic approach and the expected benefits of any cochlear implant surgery in about half of infants with non-syndromic congenital USNHL.Supplementary Table1.


The impact of age-related hearing loss extends beyond the auditory pathway and impacts brain areas related to cognitive impairment and even dementia. The presence of tinnitus, a sensation of sound that frequently co-occurs with hearing loss, is additionally linked to cognitive decline. Interestingly, structural neuroimaging studies have reported that hearing loss may precede or modulate the onset of cognitive impairment. In this study, we aimed to disentangle the effects of age, hearing loss, and tinnitus on gray matter structure. In total, 39 participants with hearing loss and tinnitus, 21 with hearing loss but without tinnitus, and 39 controls were included in this voxel- and surface-based morphometry MRI study. Whole brain volume and surface thickness measures were compared between the groups. Age-related gray matter volume decline was observed in all groups. Several brain areas showed smaller gray matter volume and cortical surface thickness in hearing loss without tinnitus, relative to controls. This reduction was observed both within and outside of the auditory pathway. Interestingly, these reductions were not observed in participants with tinnitus, who had similar hearing loss and were of similar age. Since we have tools to improve hearing loss, hearing screening may aid in the battle against cognitive decline. Hearing loss not only has an impact on the quality of hearing, it is also associated with an increased likelihood of cognitive impairments and even dementia. Presently, with a globally ageing population, the prevalence of hearing loss is rising2 together with the interest in the impact of acquired and age-related hearing loss on the brain. In light of this, it has become clear that sensory impairments are not restricted to the peripheral sensory organs, i.e. the ear, and changes to the brain are involved too6. Correspondingly, hearing loss related brain changes appear to affect other faculties than hearing. Several studies have reported a relation between age-related hearing loss, or presbycusis, and poorer cognitive functioning and even dementia13. For instance, longitudinal data showed that hearing impairment is associated with a larger likelihood of developing cognitive impairment7. Furthermore, a recent study identified hearing loss as an independent modifiable risk factor for cognitive decline10. For a comprehensive overview, see Jafari et al., 201914. It thus appears that hearing loss and cognitive decline do not only appear in the same population, hearing loss may precede or modulate the onset of cognitive impairment. Therefore, the effect of hearing loss on the brain is a potential window to understand cortical changes related to ageing.Hearing loss is the most prevalent acquired sensory impairment and it affects a large part of the ageing population worldwide20. Furthermore, similar to hearing loss, tinnitus has been linked to an increased risk of cognitive deficits21. Several studies indicate that the presence of tinnitus has a negative impact on memory, executive functioning, and quality of life22. Interestingly, one study noted that the extent of the cognitive deficits is linked to the perceived severity of the tinnitus21. Thus, in addition to the strong link between tinnitus and hearing loss, it has been reported that tinnitus by itself has a negative impact on cognitive functioning. Therefore, the factor of tinnitus has to be considered when investigating cortical changes in a population with hearing loss.Tinnitus is a symptom that often co-occurs with hearing loss, and is characterized by the perception of sound in the absence of an external acoustic stimulus. Since there is a strong link between hearing loss and neural plasticity and a strong association between hearing loss and tinnitus, it has been hypothesized that tinnitus is linked to neuroplasticity as well27. Furthermore, VBM studies that investigated cognitive decline and presbycusis reported accelerated cortical volume decline in the presence of presbycusis29. In line with this, the results of SBM studies indicated a relationship between cognitive impairment and presbycusis. These surface-based studies identified gray matter atrophy in the primary auditory cortex, the cingulate cortex, the precuneus, the insula, and the parietal cortex in the presence of presbycusis30. Surprisingly, one study reported an association between hearing loss and an increase in the gray matter of the right angular gyrus31. Nevertheless, pervasive decreases in gray matter volume and surface thickness, which are generally associated with cognitive decline, may additionally be linked to age-related hearing loss.To date, neuro-imaging studies identified several changes in gray-matter brain volume related to presbycusis (i.e. age-related hearing loss), either with Voxel-Based-Morphometry (VBM), Surface-Based-Morphometry (SBM) or other types of automated morphometry. The reported affected areas extend beyond the auditory pathway and correspond to areas related to cognitive impairment and dementia. In both unilateral and bilateral hearing loss, the decrease in brain volume in the auditory cortex, anterior cingulate, and prefrontal cortex correlated with the loss in hearing sensitivity37, the subcallosal area38, precuneus32, supra marginal gyrus33, orbitofrontal cortices39, cingulate36, insular cortex36, and the pre- and postcentral gyrus36. However, the manifestation of this effect in the temporal and thalamic areas is variable in these previously published studies. For the temporal area, it has been reported that an increase in auditory cortex gray matter related to the presence of tinnitus39, whereas tinnitus distress related to a decrease in auditory cortex gray matter36. Similarly, for the thalamus both increases and decreases in volume were reported38. Overall, the reported changes in cortical structure that are associated with tinnitus vary between studies, and are in some instances contradictory. The heterogeneity of the tinnitus population, the confound of hearing loss, differences in age as well as non-corresponding techniques and lenient statistical thresholds have been named as contributing factors to this discrepancy40.Furthermore, recent neuroimaging studies have tried to identify the central correlate of tinnitus. These studies identified changes in gray matter volume in auditory, prefrontal, and limbic areas that were associated with the presence of tinnitus or its characteristics. More specifically, reductions in gray matter were reported for the prefrontal cortexSince emerging evidence indicates that acquired hearing loss and tinnitus are associated with age-related cognitive impairment, the identification of differences in brain structure that are specific to each of these conditions may help us to develop appropriate treatments that not only aid hearing or improve tinnitus, but may additionally prevent cognitive decline. A current challenge is to determine if the structural characteristics that might contribute to cognitive impairment should be attributed to hearing loss, to tinnitus, or related factors such as age. Hence, the aim of this study was to disentangle the effects of age, acquired hearing loss, and tinnitus on the gray matter of the brain.The data of 89 participants are presented, of which 39 had tinnitus and hearing loss (THL group), 21 participants had hearing loss but no tinnitus (HL group), and 39 controls with neither tinnitus and no or minimal hearing loss (CO group). Table A voxel-based multiple regression model was used to explain differences in gray matter volume in terms of age, sex, the presence of tinnitus, and average hearing loss (HF-PTA). In addition, Total Intracranial Volume (TIV) was included as a covariate. This analysis demonstrated that age was a significant predictor for gray matter volume in our study sample (family-wise error (FWE) < 0.05, cluster size k > 20; see Table Pair-wise comparisons on volumetric data of the three participant groups were investigated with Threshold Free Cluster Enhanced (TFCE) two-sample t-tests, that were performed on the modulated gray-matter volume. The pairwise group comparisons tested were: tinnitus and hearing loss versus hearing loss (THL vs. HL), hearing loss versus controls (HL vs. CO), and tinnitus and hearing loss versus controls (THL vs. CO). In addition, the inverse of all these comparisons was tested, resulting in a total of six pair-wise group comparisons. All of the pair-wise comparisons were controlled for age and TIV.The first analysis revealed a difference in gray matter volume between the two hearing loss groups, with and without tinnitus (THL vs. HL). This group comparison showed significantly higher gray matter volume in the bilateral Lingual Gyrus /277(R)) for the tinnitus group; see Fig. 41. The cortical thickness was significantly reduced in the hearing loss group without tinnitus compared to the control group. This reduction was observed in the left supramarginal gyrus and angular gyrus, extending posteriorly to the inferior parietal gyrus, and the left lateral occipital, middle temporal, and inferior temporal areas  was performed to measure cortical thickness and gyrification29. Three ROI areas were included: the visual cortex (V1), motor cortex (M1), and the auditory cortex (A1). ROI determination was performed using the HCP_MMP1 atlas for the thickness parcellations, and the atlas provided by Neuromorphometric Inc. for the volume parcellations42.To assess if the auditory cortex is distinctively affected by age in comparison to other primary sensory or motor related areas, post-hoc region-of-interest (ROI) analyses were performed on both the gray matter volume and the surface-based thickness data, inspired by Profant et al.The group differences in surface thickness and volume of gray matter that were identified in the three ROIs are depicted in Fig. The aim of this study was to disentangle the effect of age, hearing loss, and tinnitus on the structure of cortical gray matter. Three groups were included: (1) hearing loss and tinnitus, (2) hearing loss without tinnitus, and (3) controls without hearing loss or tinnitus. The first result is that age was significantly related to gray matter volume decline in all three groups. Second, in the hearing loss group with tinnitus significantly higher gray matter volume was observed in the lingual gyri compared to the hearing loss group without tinnitus. Third, in hearing loss without tinnitus significant gray matter reductions, relative to controls, were observed in the temporal gyri, orbitofrontal area, cingulate cortex, fusiform gyrus, and the temporopolar area. Additionally, the thickness of the cortical surface was significantly less in the supramarginal gyrus, inferior parietal area, lateral occipital area, middle temporal and inferior temporal areas in hearing loss without tinnitus, compared to controls. These reductions were not observed in hearing loss participants with tinnitus, who were of similar age and had similar hearing thresholds.45. Our post-hoc analysis on gray matter volume of the visual, motor, and auditory cortices showed a larger effect of age on the auditory than on the visual and sensorimotor cortex. Note that a part of the participants in our study were hearing impaired, either with or without tinnitus. Overall, age appears to have a more detrimental impact on the auditory cortex than it does on the visual or motor cortices. Moreover, hearing loss appears to selectively aggravate the detrimental effect of age on the gray matter of the auditory cortex.The multivariate analysis of the association between age, hearing loss, and tinnitus showed that age is significantly related to gray matter volume reductions. This effect was observed in the auditory cortices, in the cingulate areas, and in the orbitofrontal area. These specific brain areas have been described in other studies on aging and brain volume28. Similarly, our surface based thickness measure indicated that hearing loss without tinnitus is related to less gray matter thickness in the parietal cortex and insula, which is in line with the reported results of an earlier study30. Hearing loss, in addition to age, is thus related to a reduction in the cortical volume and thickness of areas within and beyond the auditory system.In addition to the effect of age, acquired hearing loss has a distinct effect on the gray matter brain volume of the temporal gyri, the orbitofrontal cortex, middle cingulate and fusiform gyrus. Moreover, in the present study hearing loss was associated with differences in the cortical surface thickness of the supramarginal gyrus, angular gyrus, inferior parietal area, occipital and temporal areas. Our results are in agreement with previous reports on reduced gray matter volume in the temporal lobes and cingulate area of individuals with hearing loss24 that structural changes are more pronounced in hearing loss without tinnitus than in hearing loss with tinnitus. In line with this, the hearing loss group without tinnitus in our study had significantly lower gray matter volume and surface thickness in several areas compared to controls, whereas the hearing loss group with tinnitus did not. Likewise, Husain et al.24 reported no significant differences in gray matter volume between hearing loss with tinnitus and healthy controls in participants with hearing thresholds similar to our study. Interestingly, this finding suggests that in hearing loss the additional presence of tinnitus is related to a more limited decline in gray matter and thus better preservation of gray matter in several temporal, frontal, and occipital areas.Our results support the finding of the study by Husain et al.46 and decreased connectivity of the left lingual gyrus with the auditory resting state network47 compared to controls with normal hearing. Studies that compared tinnitus participants to hearing loss matched controls reported increased connectivity of the bilateral lingual gyrus with the attention and short-term memory networks48, increased connectivity of the lingual gyri with the default mode network, and a trend towards decreased connectivity with the auditory resting state network47. Our results indicate that in the presence of tinnitus the gray matter volume of the lingual gyrus is altered along with the functional connectivity differences reported in literature. To our knowledge there is currently no research published on specific structural preservation of the lingual gyrus in relation to tinnitus. The precise role of the lingual gyrus in tinnitus remains unclear. Other studies reported that the lingual gyrus is linked to better preserved cognitive function in patients with major depressive disorder49, and that larger lingual gyrus volume correlated with better performance on memory tasks51. In summary, these results suggest a relation between the possible preservation of cognitive functions mediated by the lingual gyrus and the presence of tinnitus.In the hearing loss group with tinnitus, the gray matter volume of the lingual gyri was larger than in those without tinnitus. Previously, the lingual gyrus has been connected to tinnitus in studies that investigated resting-state connectivity. These studies reported tinnitus related increases in connectivity of the left lingual gyrus with the left auditory cortex39, the supra marginal gyrus33, insular cortex36, and cingulate area36 were reported. Yet, our study showed that changes in these areas were related to age, and differences in the gray matter of the cingulate area were related to hearing loss. These findings are consistent with the results of Wong et al.27. In their study it was reported that a significant relation was present between age, not hearing loss, and surface thickness of the superior frontal gyrus. In addition to the aforementioned areas, other studies reported differences in the subcallosal area38, and the pre and postcentral gyrus36 in relation to tinnitus. However, in our study no significant differences were identified that related to these areas in any of our contrasts. In line with previous reports, the right cluster identified in the lingual gyrus expanded to include the precuneus32. To elaborate, if age was omitted as a covariate in our analyses or if we used an uncorrected threshold this resulted in the detection of significant volumetric differences related to hearing loss in the aforementioned areas. Since tinnitus patients often have additional hearing loss and are generally older than control groups, these confounds may explain the uncertainty and contradictory reports on structural differences in tinnitus52. Therefore, some of the results described in earlier studies may reflect  differences in hearing loss or age, and are not specifically related to the presence of tinnitus.The present study showed that larger gray matter volume in the lingual gyri was specifically related to the presence of tinnitus in individuals with hearing loss. In contrast, previous studies reported tinnitus related reductions in gray matter volume or surface thickness in multiple areas. For instance, differences in the prefrontal cortex28 and surface thickness30 in hearing loss and cognitive impairment. Atrophy of several brain areas beyond the primary auditory system has been related to hearing loss, and this widespread loss of cortical gray matter has the potential to affect a wide range of cortical processes that extend beyond auditory processing. The gray matter areas identified in our study are consistent with those reported in previous longitudinal studies that indicated that in age-related hearing loss the decline in these gray matter areas is progressive over time and relates to cognitive impairments28.Our results showed that, regardless of age, several brain areas contained less gray matter in participants with hearing loss, and this effect is more pronounced in hearing loss without tinnitus than in hearing loss with tinnitus. The areas identified in our analyses are in line with areas that are reported to show an aggravated decline of cortical volume54. Directionality of this effect has been suggested, for example the proposal that a decline in central functioning may contribute to poorer speech understanding and thus that cognition can have a big impact on hearing related processes55. Moreover, presumably the declining processing speed is the common cause of both cognitive decline and hearing loss, since the auditory system relies on precise timing and a reduction in temporal fine structure can hinder speech processing. On the other hand it has been described that central hearing disorders, or central auditory dysfunctions, often precede cognitive impairment56. The latter finding suggests that central hearing dysfunction can be an early marker of cognitive decline. Based on our results, uncompensated hearing loss without tinnitus is linked to a loss of gray matter in several cortical areas that are implicated in cognitive decline, whereas in the presence of tinnitus these areas are better preserved.The nature of the relation between hearing loss and cognitive decline is still debated. It has been suggested that a similar mechanism of progressive loss of brain efficiency can result in both central hearing loss and cognitive declineOverall, it is important to note that the differences between participant groups may have developed as a result of hearing loss or tinnitus. Alternatively, differences may have existed before tinnitus or hearing loss developed. For example, it is conceivable that some pre-existing morphological characteristics correspond to a susceptibility to develop hearing loss or tinnitus. Based on our study, we cannot distinguish between gray matter differences that developed over time and pre-existing conditions. An additional factor that may influence the outcomes is that none of our participants had hearing aids to compensate for their hearing loss, or tinnitus maskers to alleviate their tinnitus. Hearing aids and tinnitus maskers may impact the brain by generating more input and hence affect cortical plasticity.The effect of tinnitus on gray matter morphology in this study was derived from the contrast between hearing loss without tinnitus compared to hearing loss with tinnitus. Our results may thus only pertain to tinnitus associated with hearing loss. The possibility exists that tinnitus without the presence of hearing loss affects the gray matter morphology in a different manner.This study showed age-related gray matter atrophy in several brain areas, both within and outside of the auditory pathway. With the aid of volumetric and surface-based methods, we showed that age-related hearing loss without tinnitus is related to additional decreases in brain volume of the temporal, frontal, cingular, and parietal areas. The largest differences in gray matter morphometry were caused by age, after which the presence of hearing loss was associated most strongly with a decline in cortical gray matter. Interestingly, the addition of tinnitus in hearing loss individuals appears to reduce the amount of gray matter decline since the gray matter of the hearing loss with tinnitus was not significantly different from that of the control group. The lingual gyrus in particular is larger or better preserved in the presence of tinnitus. These findings confirm that hearing loss has impact beyond the auditory system and is an important factor to consider in the treatment of cognitive impairments.One hundred and thirteen participants were included in a larger MRI study at the University Medical Center Groningen, the Netherlands. Three people did not complete all aspects of the research, one data file was corrupted in the transfer process, and in an additional nine scans either the contrast between white and grey matter was insufficient for the segmentation algorithm to work reliably, or movement during anatomical scanning rendered the data with artefacts. This resulted in complete and sufficient data for a total of 99 participants, of which 39 had tinnitus and hearing loss, 21 participants with hearing loss but without tinnitus, and 39 healthy controls with no tinnitus and no or minimal hearing loss. The study was approved by the Medical Ethical Committee of the University of Groningen, performed in accordance with all relevant regulations and informed consent was obtained from all participants.The hearing levels of all participants were assessed with pure tone audiometry. Thresholds were determined in a sound attenuating booth for octave frequencies ranging from 0.25 to 8 kHz, and additionally at 3 and 6 kHz. The average hearing loss was quantified as the mean of the hearing thresholds at 2, 4, and 8 kHz of both ears . A matching procedure was used to estimate tinnitus pitch and loudness. The majority of the participants perceived high frequency tinnitus , and the remaining four participants reported the perception of broadband noise. None of the participants compensated their hearing loss with hearing aids, or ameliorated their tinnitus with maskers. Participants were required to have hearing thresholds better than 40 dB SPL at 1 kHz to meet the inclusion criteria for a functional task-based scan that was obtained in the same sequence as the anatomical images. This resulted in the inclusion of participants with high frequency hearing loss only.MRI scanning was performed at the Neuro Imaging Center in Groningen, on a 3.0 T Philips Intera MRI scanner . A SENSE 32-channel head coil was used to obtain a whole brain T1 weighted anatomical image with a voxel size of 1 × 1 × 1 mm .41, and included segmentation, normalization and smoothing. Total Intracranial Volume (TIV) was estimated for all participants to correct for differences in head and brain size. After these steps were performed, a sample quality check was run on the segmented images to determine if image quality was sufficiently high; all included images scored above 86%. This score is based on a measure of homogeneity of the sample and is used to determine image quality after pre-processing (i.e. mean correlation measure) and it was run with TIV as a nuisance variable. Data with a low mean correlation  or large differences to the mean score were manually checked for sufficient image quality. If this confirmed the low image quality, images were excluded from further analysis.All T1-images were aligned according to the individual anatomical anterior–posterior commissures in Vistasoft-Master, software run in Matlab2018a. Further analyses were done in CAT12, a structural imaging-oriented SPM toolboxThe included images were smoothed with an 8-mm Gaussian kernel. The subsequent analyses were performed on the modulated gray matter volume images (VBM) and the surface-based thickness measures (SBM). Modulated gray matter images were scaled by the amount of contraction induced by non-linear spatial normalization. The value of each voxel was multiplied with the Jacobian determinant obtained with spatial normalization. After the pre-processing and first level analysis, second level whole group and group wise analyses were performed .57. This non-linear method can detect both diffuse low-amplitude signals and sharp focal signals. In order to test for statistical significance, TFCE computes p-values for each voxel via permutation testing.A multiple regression model was run on the modulated gray matter images with sex, age, the presence of tinnitus, and average hearing loss as covariates to check the association between these covariates and the gray matter volume data. Then, two sample t-tests were performed on both the gray matter volume and surface-based thickness measures to test group differences in a pairwise manner. Threshold Free Cluster Enhancement (TFCE) was used to assess the cluster-wise differences in gray matter volume between the groups