OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate.

AIMS: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. METHODS: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. RESULTS: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study. CONCLUSION: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups.

The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records.

AIMS: The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity ensuring safety and appropriateness of prescribing. A disruption could have significant negative implications for patient care. Using routinely collected data, our aim was first to describe codes used to record medication review activity and then to report the impact of COVID-19 on the rates of medication reviews. METHODS: With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. For each month, between April 2019 and March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months with breakdowns by regional, clinical and demographic subgroups and those prescribed high-risk medications. RESULTS: In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity decreased (-21.1% April 2020), but the 12-month rate was not substantially impacted (-10.5% March 2021). The rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high-risk groups (care home residents 34.1%, age 90+ years 13.1%, high-risk medications 10.2%). The most used medication review code was Medication review done 314530002 (59.5%). CONCLUSIONS: There was a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period. Structured medication reviews were prioritized for high-risk patients.

A systems framework for implementing healthy food retail in grocery settings.

BACKGROUND: Food retailers can be reluctant to initiate healthy food retail activities in the face of a complex set of interrelated drivers that impact the retail environment. The Systems Thinking Approach for Retail Transformation (START) is a determinants framework created using qualitative systems modelling to guide healthy food retail interventions in community-based, health-promoting settings. We aimed to test the applicability of the START map to a suite of distinct healthy food marketing and promotion activities that formed an intervention in a grocery setting in regional Victoria, Australia. METHODS: A secondary analysis was undertaken of 16 previously completed semi-structured interviews with independent grocery retailers and stakeholders. Interviews were deductively coded against the existing START framework, whilst allowing for new grocery-setting specific factors to be identified. New factors and relationships were used to build causal loop diagrams and extend the original START systems map using Vensim. RESULTS: A version of the START map including aspects relevant to the grocery setting was developed ("START-G"). In both health-promoting and grocery settings, it was important for retailers to 'Get Started' with healthy food retail interventions that were supported by a proof-of-concept and 'Focus on the customer' response (with grocery-settings focused on monitoring sales data). New factors and relationships described perceived difficulties associated with disrupting a grocery-setting 'Supply-side status quo' that promotes less healthy food and beverage options. Yet, most grocery retailers discussed relationships that highlighted the potential for 'Healthy food as innovation' and 'Supporting cultural change through corporate social responsibility and leadership'. CONCLUSIONS: Several differences were found when implementing healthy food retail in grocery compared to health promotion settings. The START-G map offers preliminary guidance for identifying and addressing commercial interests in grocery settings that currently promote less healthy foods and beverages, including by starting to address business outcomes and supplier relationships.

When primary healthcare meets queerstory: community-based system dynamics influencing regional/rural LGBTQ + people's access to quality primary healthcare in Australia.

BACKGROUND: Lesbian, gay, bisexual, transgender, Queer, and people of any other minority sexuality or gender identity (LGBTQ + or "Queer") are often marginalised from accessing quality primary healthcare (PHC) in their local community. This is largely due to Queerphobic, cis-heteronormative/sexist systems pathologising Queer life and identities. The study aims were to: (1) identify key priorities for increasing Queer people's access to quality PHC as told by Queer people themselves, (2) identify the feedback loops that reduce or support Queer people's access to quality PHC in non-metropolitan, regional/rural communities, and (3) identify potential action areas to improve system structures to increase Queer people's access to quality PHC. METHODS: Group Model Building (GMB) workshops were held with a small group (n = 8) of LGBTQ + people in regional Victoria with lived experience of using PHC services. This participatory approach permits exploration and visual mapping of local structures causing behaviour patterns of community concern over time - in this case, Queer people's ability to access quality PHC in the Geelong-Barwon region. This is the first study that specially applies GMB in Queer PHC in the non-metropolitan regional/rural context. RESULTS: Key community identified PHC priorities were: (a) providers' level of Queer Literacy, (b) the responsibility of Queer Advocacy (at individual, systemic, and collective levels), (c) support from safe Queer Spaces, (d) strength from a Queer Presence, and (e) power from Intersectional Queer Life. These priorities interconnected, creating system-level feedback loops reinforcing barriers and enablers to Queer people's access to quality PHC in the Geelong-Barwon region; with potential action areas identified. CONCLUSIONS: Improving Queer people's access to quality PHC in the Geelong-Barwon region requires embedding principles of Queer Literacy, Queer Advocacy, Queer Space, Queer Presence, and Intersectional Queer Life within practices and service systems. The study findings were distilled into a novel, preliminary set of Queer Equity Principles. These need to be taken back to regional Queer communities for further co-design and planning for translation across PHC practices and systems, with potential applicability in other areas of the healthcare spectrum.

System dynamics modelling to engage community stakeholders in addressing water and sugar sweetened beverage consumption.

BACKGROUND: Participatory approaches to develop community-based system dynamics models to tackle complexity are promising, but research is needed in how simulation models can be developed with community stakeholders to yield significant system insights. This study presents the results of a community-based system dynamics modelling process to increase water consumption and decrease sugar sweetened beverage consumption in Portland, Victoria, a regional town in Australia. METHODS: A series of group model building workshops with 11 community stakeholders addressing the topic of water and sugar sweetened beverage consumption was conducted in Portland. A simulating system dynamics model was built with stakeholders to inform action planning. RESULTS: A system dynamics model was created to provide insight into water and sugar sweetened beverage consumption in Portland. The model included six feedback loops describing the causal effects of sugar sweetened beverage consumption habits and norms, water taste, water consumption norms, public water availability, and public health benefits. For example, the sugar sweetened beverage consumption norm loop modelled how people overestimating others' consumption may motivate an increase in their own consumption, feeding back and further amplifying an increase in sugar sweetened beverage consumption. The model contributed to the foundation of a strong partnership to improve the taste of water and educate the public on water consumption. CONCLUSIONS: Engaging stakeholders in system dynamics modelling about water and sugar sweetened beverage consumption increased engagement and collaboration to address the problem among community stakeholders.

System approaches to childhood obesity prevention: ground up experience of adaptation and real-world context.

OBJECTIVE: Childhood obesity prevention is critical to reducing the health and economic burden currently experienced by the Australian economy. System science has emerged as an approach to manage the complexity of childhood obesity and the ever-changing risk factors, resources and priorities of government and funders. Anecdotally, our experience suggests that inflexibility of traditional research methods and dense academic terminology created issues with those working in prevention practice. Therefore, this paper provides a refined description of research-specific terminology of scale-up, fidelity, adaptation and context, drawing from community-based system dynamics and our experience in designing, implementing and evaluating non-linear, community-led system approaches to childhood obesity prevention. DESIGN: We acknowledge the importance of using a practice lens, rather than purely a research design lens, and provide a narrative on our experience and perspectives on scale-up, fidelity, context and adaptation through a practice lens. SETTING: Communities. PARTICIPANTS: Practice-based researcher experience and perspectives. RESULTS: Practice-based researchers highlighted the key finding that community should be placed at the centre of the intervention logic. This allowed communities to self-organise with regard to stakeholder involvement, capacity, boundary identification, and co-creation of actions implemented to address childhood obesity will ensure scale-up, fidelity, context and adaptation are embedded. CONCLUSIONS: We need to measure beyond primary anthropometric outcomes and focus on evaluating more about implementation, process and sustainability. We need to learn more from practitioners on the ground and use an implementation science lens to further understand how actions work. This is where solutions to sustained childhood obesity prevention will be found.

Normative Study of the Binaural Interaction Component of the Human Auditory Brainstem Response as a Function of Interaural Time Differences.

OBJECTIVES: The binaural interaction component (BIC) of the auditory brainstem response (ABR) is obtained by subtracting the sum of the monaural right and left ear ABRs from the binaurally evoked ABR. The result is a small but prominent negative peak (herein called "DN1"), indicating a smaller binaural than summed ABR, which occurs around the latency of wave V or its roll-off slope. The BIC has been proposed to have diagnostic value as a biomarker of binaural processing abilities; however, there have been conflicting reports regarding the reliability of BIC measures in human subjects. The objectives of the current study were to: (1) examine prevalence of BIC across a large group of normal-hearing young adults; (2) determine effects of interaural time differences (ITDs) on BIC; and (3) examine any relationship between BIC and behavioral ITD discrimination acuity. DESIGN: Subjects were 40 normal-hearing adults (20 males and 20 females), aged 21 to 48 years, with no history of otologic or neurologic disorders. Midline ABRs were recorded from electrodes at high forehead (Fz) referenced to the nape of the neck (near the seventh cervical vertebra), with Fpz (low forehead) as the ground. ABRs were also recorded with a conventional earlobe reference for comparison to midline results. Stimuli were 90 dB peSPL biphasic clicks. For BIC measurements, stimuli were presented in a block as interleaved right monaural, left monaural, and binaural stimuli with 2000+ presentations per condition. Four measurements were averaged for a total of 8000+ stimuli per analyzed waveform. BIC was measured for ITD = 0 (simultaneous bilateral) and for ITDs of ±500 and ±750 µs. Subjects separately performed a lateralization task, using the same stimuli, to determine ITD discrimination thresholds. RESULTS: An identifiable BIC DN1 was obtained in 39 of 40 subjects at ITD = 0 µs in at least one of two measurement sessions, but was seen in lesser numbers of subjects in a single session or as ITD increased. BIC was most often seen when a subject was relaxed or sleeping, and less often when they fidgeted or reported neck tension, suggesting myogenic activity as a possible factor in disrupting BIC measurements. Mean BIC latencies systematically increased with increasing ITD, and mean BIC amplitudes tended to decrease. However, across subjects, there was no significant relationship between the amplitude or latency of the BIC and behavioral ITD thresholds. CONCLUSIONS: Consistent with previous studies, measurement of the BIC was time consuming and a BIC was sometimes difficult to obtain in awake normal-hearing subjects. The BIC will thus continue to be of limited clinical utility unless stimulus parameters and measurement techniques can be identified that produce a more robust response. Nonetheless, modulation of BIC characteristics by ITD supports the concept that the ABR BIC indexes aspects of binaural brainstem processing and thus may prove useful in selected research applications, e.g. in the examination of populations expected to have aberrant binaural signal processing ability.

Effects of interaural decoherence on sensitivity to interaural level differences across frequency.

The interaural level difference (ILD) is a robust indicator of sound source azimuth, and human ILD sensitivity persists under conditions that degrade normally-dominant interaural time difference (ITD) cues. Nonetheless, ILD sensitivity varies somewhat with both stimulus frequency and interaural correlation (coherence). To further investigate the combined binaural perceptual influence of these variables, the present study assessed ILD sensitivity at frequencies 250-4000 Hz using stimuli of varied interaural correlation. In the first of two experiments, ILD discrimination thresholds were modestly elevated, and subjective lateralization slightly reduced, for both half-correlated and uncorrelated narrowband noise tokens relative to correlated tokens. Different from thresholds in the correlated condition, which were worst at 1000 Hz [Grantham, D.W. (1984). J. Acoust. Soc. Am. 75, 1191-1194], thresholds in the decorrelated conditions were independent of frequency. However, intrinsic envelope fluctuations in narrowband stimuli caused moment-to-moment variation of the nominal ILD, complicating interpretation of measured thresholds. Thus, a second experiment employed low-fluctuation noise tokens, revealing a clear effect of interaural decoherence per se that was strongly frequency-dependent, decreasing in magnitude from low to high frequencies. Measurements are consistent with known integration times in ILD-sensitive neurons and also suggest persistent influences of covert ITD cues in putative "ILD" tasks.

An investigation into the use of < 38 µm fraction as a proxy for < 10 µm road dust particles.

It is well documented that a large portion of urban particulate matters is derived from road dust. Isolating particles of RD which are small enough to be inhaled, however, is a difficult process. In this study, it is shown for the first time that the < 38 µm fraction of road dust particles can be used as a proxy for road dust particles < 10 µm in bioaccessibility studies. This study probed similarities between the < 10 and < 38µm fractions of urban road dust to show that the larger of the two can be used for analysis for which larger sample masses are required, as is the case with in vitro analysis. Road dust, initially segregated to size < 38 µm using sieves, was again size segregated to < 10 µm using water deposition. Both the original < 38 µm and the separated < 10 µm fractions were then subject to single particle analysis by SEM-EDX and bulk analysis by ICP-OES for its elemental composition. Dissolution tests in artificial lysosomal fluid, representative of lung fluid, were carried out on both samples to determine % bioaccessibility of selected potentially harmful elements and thus probe similarities/differences in in vitro behaviour between the two fractions. The separation technique achieved 94.3% of particles < 10 µm in terms of number of particles (the original sample contained 90.4% as determined by SEM-EDX). Acid-soluble metal concentration results indicated differences between the samples. However, when manipulated to negate the input of Si, SEM-EDX data showed general similarities in metal concentrations. Dissolution testing results indicated similar behaviour between the two samples in a simulated biological fluid.

A scoping study of component-specific toxicity of mercury in urban road dusts from three international locations.

This scoping study presents an investigation of the total and bioaccessible mercury concentrations in road dust (RD) from three international urban sites, where a one-off sampling campaign was conducted at each. This was done to address the hypothesis that the matrix in which mercury is found influences its ability to become accessible to the body once inhaled. For that purpose, the samples were analysed for total and pulmonary bioaccessible mercury and the data compared to the chemical structure of individual particles by SEM. The results obtained from this study suggest that a high mercury content does not necessarily equate to high bioaccessibility, a phenomenon which could be ascribed to the chemical character of the individual particles. It was found that the Manchester samples contained more pulmonary soluble mercury species (as determined by elemental associations of Hg and Cl) in comparison to the other two samples, Curitiba, Brazil, and Johannesburg, South Africa. This finding ultimately underlines the necessity to conduct a site-specific in-depth analysis of RD, to determine the concentration, chemical structure and molecular speciation of the materials within the complex matrix of RD. Therefore, rather than simply assuming that higher bulk concentrations equate to more significant potential human health concerns, the leaching potential of the metal/element in its specific form (for example as a mineral) should be ascertained. The importance of individual particle behaviour in the determination of human health risk is therefore highlighted.

Between-ear sound frequency disparity modulates a brain stem biomarker of binaural hearing.

The auditory brain stem response (ABR) is an evoked potential that indexes a cascade of neural events elicited by sound. In the present study we evaluated the influence of sound frequency on a derived component of the ABR known as the binaural interaction component (BIC). Specifically, we evaluated the effect of acoustic interaural (between-ear) frequency mismatch on BIC amplitude. Goals were to 1) increase basic understanding of sound features that influence this long-studied auditory potential and 2) gain insight about the persistence of the BIC with interaural electrode mismatch in human users of bilateral cochlear implants, presently a limitation on the prospective utility of the BIC in audiological settings. Data were collected in an animal model that is audiometrically similar to humans, the chinchilla (Chinchilla lanigera; 6 females). Frequency disparities and amplitudes of acoustic stimuli were varied over broad ranges, and associated variation of BIC amplitude was quantified. Subsequently, responses were simulated with the use of established models of the brain stem pathway thought to underlie the BIC. Collectively, the data demonstrate that at high sound intensities (≥85 dB SPL), the acoustically elicited BIC persisted with interaurally disparate stimulation (click frequencies ≥1.5 octaves apart). However, sharper tuning emerged at moderate sound intensities (65 dB SPL), with the largest BIC occurring for stimulus frequencies within ~0.8 octaves, equivalent to ±1 mm in cochlear place. Such responses were consistent with simulated responses of the presumed brain stem generator of the BIC, the lateral superior olive. The data suggest that leveraging focused electrical stimulation strategies could improve BIC-based bilateral cochlear implant fitting outcomes.NEW & NOTEWORTHY Traditional hearing tests evaluate each ear independently. Diagnosis and treatment of binaural hearing dysfunction remains a basic challenge for hearing clinicians. We demonstrate in an animal model that the prospective utility of a noninvasive electrophysiological signature of binaural function, the binaural interaction component (BIC), depends strongly on the intensity of auditory stimulation. Data suggest that more informative BIC measurements could be obtained with clinical protocols leveraging stimuli restricted in effective bandwidth.

Auditory evoked potentials of the plainfin midshipman fish (Porichthys notatus): implications for directional hearing.

The plainfin midshipman (Porichthys notatus) is an acoustically communicative teleost fish. Here, we evaluated auditory evoked potentials (AEPs) in reproductive female midshipman exposed to tones at or near dominant frequencies of the male midshipman advertisement call. An initial series of experiments characterized AEPs at behaviorally relevant suprathreshold sound levels (130-140 dB SPL re. 1 µPa). AEPs decreased in magnitude with increasing stimulus frequency and featured a stereotyped component at twice the stimulus frequency. Recording electrode position was varied systematically and found to affect AEP magnitude and phase characteristics. Later experiments employed stimuli of a single frequency to evaluate contributions of the saccule to the AEP, with particular attention to the effects of sound source azimuth on AEP amplitude. Unilateral excision of saccular otoliths (sagittae) decreased AEP amplitude; unexpectedly, decreases differed for right versus left otolith excision. A final set of experiments manipulated the sound pressure-responsive swim bladder. Swim bladder excision further reduced the magnitude of AEP responses, effectively eliminating responses at the standard test intensity (130 dB SPL) in some animals. Higher-intensity stimulation yielded response minima at forward azimuths ipsilateral to the excised sagitta, but average cross-azimuth modulation generally remained slight. Collectively, the data underscore that electrode position is an essential variable to control in fish AEP studies and suggest that in female midshipman: (1) the saccule contributes to the AEP, but its directionality as indexed by the AEP is limited, (2) a left-right auditory asymmetry may exist and (3) the swim bladder provides gain in auditory sensitivity that may be important for advertisement call detection and phonotaxis.

Representation of Multidimensional Stimuli: Quantifying the Most Informative Stimulus Dimension from Neural Responses.

A common way to assess the function of sensory neurons is to measure the number of spikes produced by individual neurons while systematically varying a given dimension of the stimulus. Such measured tuning curves can then be used to quantify the accuracy of the neural representation of the stimulus dimension under study, which can in turn be related to behavioral performance. However, tuning curves often change shape when other dimensions of the stimulus are varied, reflecting the simultaneous sensitivity of neurons to multiple stimulus features. Here we illustrate how one-dimensional information analyses are misleading in this context, and propose a framework derived from Fisher information that allows the quantification of information carried by neurons in multidimensional stimulus spaces. We use this method to probe the representation of sound localization in auditory neurons of chinchillas and guinea pigs of both sexes, and show how heterogeneous tuning properties contribute to a representation of sound source position that is robust to changes in sound level.SIGNIFICANCE STATEMENT Sensory neurons' responses are typically modulated simultaneously by numerous stimulus properties, which can result in an overestimation of neural acuity with existing one-dimensional neural information transmission measures. To overcome this limitation, we develop new, compact expressions of Fisher information-derived measures that bound the robust encoding of separate stimulus dimensions in the context of multidimensional stimuli. We apply this method to the problem of the representation of sound source location in the face of changes in sound source level by neurons of the auditory midbrain.

Slow Temporal Integration Enables Robust Neural Coding and Perception of a Cue to Sound Source Location.

UNLABELLED: In mammals, localization of sound sources in azimuth depends on sensitivity to interaural differences in sound timing (ITD) and level (ILD). Paradoxically, while typical ILD-sensitive neurons of the auditory brainstem require millisecond synchrony of excitatory and inhibitory inputs for the encoding of ILDs, human and animal behavioral ILD sensitivity is robust to temporal stimulus degradations (e.g., interaural decorrelation due to reverberation), or, in humans, bilateral clinical device processing. Here we demonstrate that behavioral ILD sensitivity is only modestly degraded with even complete decorrelation of left- and right-ear signals, suggesting the existence of a highly integrative ILD-coding mechanism. Correspondingly, we find that a majority of auditory midbrain neurons in the central nucleus of the inferior colliculus (of chinchilla) effectively encode ILDs despite complete decorrelation of left- and right-ear signals. We show that such responses can be accounted for by relatively long windows of bilateral excitatory-inhibitory interaction, which we explicitly measure using trains of narrowband clicks. Neural and behavioral data are compared with the outputs of a simple model of ILD processing with a single free parameter, the duration of excitatory-inhibitory interaction. Behavioral, neural, and modeling data collectively suggest that ILD sensitivity depends on binaural integration of excitation and inhibition within a ≳3 ms temporal window, significantly longer than observed in lower brainstem neurons. This relatively slow integration potentiates a unique role for the ILD system in spatial hearing that may be of particular importance when informative ITD cues are unavailable. SIGNIFICANCE STATEMENT: In mammalian hearing, interaural differences in the timing (ITD) and level (ILD) of impinging sounds carry critical information about source location. However, natural sounds are often decorrelated between the ears by reverberation and background noise, degrading the fidelity of both ITD and ILD cues. Here we demonstrate that behavioral ILD sensitivity (in humans) and neural ILD sensitivity (in single neurons of the chinchilla auditory midbrain) remain robust under stimulus conditions that render ITD cues undetectable. This result can be explained by "slow" temporal integration arising from several-millisecond-long windows of excitatory-inhibitory interaction evident in midbrain, but not brainstem, neurons. Such integrative coding can account for the preservation of ILD sensitivity despite even extreme temporal degradations in ecological acoustic stimuli.

Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats.

BACKGROUND: The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats. METHODS: Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth-restricted rats at 6 and 12 mo of age; sex steroids at 12 mo. RESULTS: Glucose intolerance was present at 6 mo of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth-restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose, and testosterone at 12 mo of age (P < 0.05). Insulin release in response to a glucose challenge was blunted in conjunction with a reduction in protein expression of pancreatic glucose transporter type 2 and estrogen receptor-α at 12 mo of age in female growth-restricted rats (P < 0.05). CONCLUSION: This study demonstrated that slow fetal growth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift toward testosterone excess at 12 mo of age in female growth-restricted rats.

Effects of Hatchery Rearing on the Structure and Function of Salmonid Mechanosensory Systems.

This paper reviews recent studies on the effects of hatchery rearing on the auditory and lateral line systems of salmonid fishes. Major conclusions are that (1) hatchery-reared juveniles exhibit abnormal lateral line morphology (relative to wild-origin conspecifics), suggesting that the hatchery environment affects lateral line structure, perhaps due to differences in the hydrodynamic conditions of hatcheries versus natural rearing environments, and (2) hatchery-reared salmonids have a high proportion of abnormal otoliths, a condition associated with reduced auditory sensitivity and suggestive of inner ear dysfunction.

Sound frequency-invariant neural coding of a frequency-dependent cue to sound source location.

The century-old duplex theory of sound localization posits that low- and high-frequency sounds are localized with two different acoustical cues, interaural time and level differences (ITDs and ILDs), respectively. While behavioral studies in humans and behavioral and neurophysiological studies in a variety of animal models have largely supported the duplex theory, behavioral sensitivity to ILD is curiously invariant across the audible spectrum. Here we demonstrate that auditory midbrain neurons in the chinchilla (Chinchilla lanigera) also encode ILDs in a frequency-invariant manner, efficiently representing the full range of acoustical ILDs experienced as a joint function of sound source frequency, azimuth, and distance. We further show, using Fisher information, that nominal "low-frequency" and "high-frequency" ILD-sensitive neural populations can discriminate ILD with similar acuity, yielding neural ILD discrimination thresholds for near-midline sources comparable to behavioral discrimination thresholds estimated for chinchillas. These findings thus suggest a revision to the duplex theory and reinforce ecological and efficiency principles that hold that neural systems have evolved to encode the spectrum of biologically relevant sensory signals to which they are naturally exposed.

Evidence for a neural source of the precedence effect in sound localization.

Normal-hearing human listeners and a variety of studied animal species localize sound sources accurately in reverberant environments by responding to the directional cues carried by the first-arriving sound rather than spurious cues carried by later-arriving reflections, which are not perceived discretely. This phenomenon is known as the precedence effect (PE) in sound localization. Despite decades of study, the biological basis of the PE remains unclear. Though the PE was once widely attributed to central processes such as synaptic inhibition in the auditory midbrain, a more recent hypothesis holds that the PE may arise essentially as a by-product of normal cochlear function. Here we evaluated the PE in a unique human patient population with demonstrated sensitivity to binaural information but without functional cochleae. Users of bilateral cochlear implants (CIs) were tested in a psychophysical task that assessed the number and location(s) of auditory images perceived for simulated source-echo (lead-lag) stimuli. A parallel experiment was conducted in a group of normal-hearing (NH) listeners. Key findings were as follows: 1) Subjects in both groups exhibited lead-lag fusion. 2) Fusion was marginally weaker in CI users than in NH listeners but could be augmented by systematically attenuating the amplitude of the lag stimulus to coarsely simulate adaptation observed in acoustically stimulated auditory nerve fibers. 3) Dominance of the lead in localization varied substantially among both NH and CI subjects but was evident in both groups. Taken together, data suggest that aspects of the PE can be elicited in CI users, who lack functional cochleae, thus suggesting that neural mechanisms are sufficient to produce the PE.