Extended frequency range hearing thresholds and otoacoustic emissions in acute acoustic trauma

We sought to evaluate the relative value of pure tone audiometry (PTA), extended high-frequency audiometry (EFA) and transiently evoked otoacoustic emissions (OAE) and distortion products when monitoring acute acoustic trauma (AAT).

Frequency-Dependent Selection Predicts Patterns of Radiations and Biodiversity

Most empirical studies support a decline in speciation rates through time, although evidence for constant speciation rates also exists. Declining rates have been explained by invoking pre-existing niches, whereas constant rates have been attributed to non-adaptive processes such as sexual selection and mutation. Trends in speciation rate and the processes underlying it remain unclear, representing a critical information gap in understanding patterns of global diversity. Here we show that the temporal trend in the speciation rate can also be explained by frequency-dependent selection. We construct a frequency-dependent and DNA sequence-based model of speciation. We compare our model to empirical diversity patterns observed for cichlid fish and Darwin's finches, two classic systems for which speciation rates and richness data exist. Negative frequency-dependent selection predicts well both the declining speciation rate found in cichlid fish and explains their species richness. For groups like the Darwin's finches, in which speciation rates are constant and diversity is lower, speciation rate is better explained by a model without frequency-dependent selection. Our analysis shows that differences in diversity may be driven by incipient species abundance with frequency-dependent selection. Our results demonstrate that genetic-distance-based speciation and frequency-dependent selection are sufficient to explain the high diversity observed in natural systems and, importantly, predict decay through time in speciation rate in the absence of pre-existing niches.

Evolution of dominance under frequency-dependent intraspecific competition

A population-genetic analysis is performed of a two-locus two-allele model, in which the primary locus has a major effect on a quantitative trait that is under frequency-dependent disruptive selection caused by intraspecific competition for a continuum of resources. The modifier locus determines the degree of dominance at the trait level. We establish the conditions when a modifier allele can invade and when it becomes fixed if sufficiently frequent. In general, these are not equivalent because an unstable internal equilibrium may exist and the condition for successful invasion of the modifier is more restrictive than that for eventual fixation from already high frequency. However, successful invasion implies global fixation, i.e., fixation from any initial condition. Modifiers of large effect can become fixed, and also invade, in a wider parameter range than modifiers of small effect. We also study modifiers with a direct, frequency-independent deleterious fitness effect. We show that they can invade if they induce a sufficiently high level of dominance and if disruptive selection on the ecological trait is strong enough. For deleterious modifiers, successful invasion no longer implies global fixation because they can become stuck at an intermediate frequency due to a stable internal equilibrium. Although the conditions for invasion and for fixation if sufficiently frequent are independent of the linkage relation between the two loci, the rate of spread depends strongly on it. The present study provides further support to the view that evolution of dominance may be an efficient mechanism to remove unfit heterozygotes that are maintained by balancing selection. It also demonstrates that an invasion analysis of mutants of very small effect is insufficient to obtain a full understanding of the evolutionary dynamics under frequency-dependent selection.

Peri-ictal correlation dynamics of high-frequency (80-200 Hz) intracranial EEG

To assess (1) how large-scale correlation of intracranial EEG signals in the high-frequency range (80-200Hz) evolves from the pre-ictal, through the ictal into the postictal state and (2) whether the contribution of local neuronal activity to large-scale EEG correlation differentiates epileptogenic from non-epileptogenic brain tissue.

Frequency-dependent social dominance in a color polymorphic cichlid fish

A mechanism commonly suggested to explain the persistence of color polymorphisms in animals is negative frequency-dependent selection. It could result from a social dominance advantage to rare morphs. We tested for this in males of red and blue color morphs of the Lake Victoria cichlid, Pundamilia. Earlier work has shown that males preferentially attack the males of their own morph, while red males are more likely to win dyadic contests with blue males. In order to study the potential contribution of both factors to the morph co-existence, we manipulated the proportion of red and blue males in experimental assemblages and studied its effect on social dominance. We then tried to disentangle the effects of the own-morph attack bias and social dominance of red using simulations. In the experiment, we found that red males were indeed socially dominant to the blue ones, but only when rare. However, blue males were not socially dominant when rare. The simulation results suggest that an own-morph attack bias reduces the social dominance of red males when they are more abundant. Thus, there is no evidence of symmetric negative frequency-dependent selection acting on social dominance, suggesting that additional fitness costs to the red morph must explain their co-existence.

Color polymorphism and intrasexual competition in assemblages of cichlid fish

The origin and maintenance of phenotypic polymorphisms is a classical problem in evolutionary ecology. Aggressive male-male competition can be a source of negative frequency-dependent selection stabilizing phenotypic polymorphisms when aggression is biased toward the own morph. We studied experimental assemblages of red and blue color morphs of the Lake Victoria cichlid fish Pundamilia. Aggression was investigated in mixed-color and single-color assemblages. We found that aggression was indeed biased toward males of the same color, which could in theory reduce aggression levels in mixed-color assemblages and promote coexistence. However, previous studies showed high aggression levels in red and dominance of red over blue males in dyadic interactions, which could hinder coexistence. We found that coexistence in mixed-color assemblages reduced the level of aggression in red males but not in blue males. Red and blue males were equally dominant in mixed-color assemblages, suggesting that predictions derived from dyadic interactions may not be valid for an assemblage situation. The results are consistent with field data: the geographic range of red is nested within that of blue, suggesting that red cannot displace blue. Our study suggests that male-male competition may be a significant force for maintaining phenotypic diversity.

EVOLUTION OF DOMINANCE UNDER FREQUENCY-DEPENDENT INTRASPECIFIC COMPETITION IN AN ASSORTATIVELY MATING POPULATION

We study the evolution of higher levels of dominance as a response to negative frequency-dependent selection. In contrast to previous studies, we focus on the effect of assortative mating on the evolution of dominance under frequency-dependent intraspecific competition. We analyze a two-locus two-allele model, in which the primary locus has a major effect on a quantitative trait that is under a mixture of frequency-independent stabilizing selection, density-dependent selection, and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The second (modifier) locus determines the degree of dominance at the trait level. Additionally, the population mates assortatively with respect to similarities in the ecological trait. Our analysis shows that the parameter region in which dominance can be established decreases if small levels of assortment are introduced. In addition, the degree of dominance that can be established also decreases. In contrast, if assortment is intermediate, sexual selection for extreme types can be established, which leads to evolution of higher levels of dominance than under random mating. For modifiers with large effects, intermediate levels of assortative mating are most favorable for the evolution of dominance. For large modifiers, the speed of fixation can even be higher for intermediate levels of assortative mating than for random mating.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

Topographic electrophysiological signatures of FMRI Resting State Networks

Background: fMRI Resting State Networks (RSNs) have gained importance in the present fMRI literature. Although their functional role is unquestioned and their physiological origin is nowadays widely accepted, little is known about their relationship to neuronal activity. The combined recording of EEG and fMRI allows the temporal correlation between fluctuations of the RSNs and the dynamics of EEG spectral amplitudes. So far, only relationships between several EEG frequency bands and some RSNs could be demonstrated, but no study accounted for the spatial distribution of frequency domain EEG. Methodology/Principal Findings: In the present study we report on the topographic association of EEG spectral fluctuations and RSN dynamics using EEG covariance mapping. All RSNs displayed significant covariance maps across a broad EEG frequency range. Cluster analysis of the found covariance maps revealed the common standard EEG frequency bands. We found significant differences between covariance maps of the different RSNs and these differences depended on the frequency band. Conclusions/Significance: Our data supports the physiological and neuronal origin of the RSNs and substantiates the assumption that the standard EEG frequency bands and their topographies can be seen as electrophysiological signatures of underlying distributed neuronal networks.

Design of a semi-implantable hearing device for direct acoustic cochlear stimulation

A new hearing therapy based on direct acoustic cochlear stimulation was developed for the treatment of severe to profound mixed hearing loss. The device efficacy was validated in an initial clinical trial with four patients. This semi-implantable investigational device consists of an externally worn audio processor, a percutaneous connector, and an implantable microactuator. The actuator is placed in the mastoid bone, right behind the external auditory canal. It generates vibrations that are directly coupled to the inner ear fluids and that, therefore, bypass the external and the middle ear. The system is able to provide an equivalent sound pressure level of 125 dB over the frequency range between 125 and 8000 Hz. The hermetically sealed actuator is designed to provide maximal output power by keeping its dimensions small enough to enable implantation. A network model is used to simulate the dynamic characteristics of the actuator to adjust its transfer function to the characteristics of the middle ear. The geometry of the different actuator components is optimized using finite-element modeling.

Speech perception benefits of internet versus conventional telephony for hearing-impaired individuals

Telephone communication is a challenge for many hearing-impaired individuals. One important technical reason for this difficulty is the restricted frequency range (0.3-3.4 kHz) of conventional landline telephones. Internet telephony (voice over Internet protocol [VoIP]) is transmitted with a larger frequency range (0.1-8 kHz) and therefore includes more frequencies relevant to speech perception. According to a recently published, laboratory-based study, the theoretical advantage of ideal VoIP conditions over conventional telephone quality has translated into improved speech perception by hearing-impaired individuals. However, the speech perception benefits of nonideal VoIP network conditions, which may occur in daily life, have not been explored. VoIP use cannot be recommended to hearing-impaired individuals before its potential under more realistic conditions has been examined.

Transient rhythmic network activity in the somatosensory cortex evoked by distributed input in vitro

The initiation and maintenance of physiological and pathophysiological oscillatory activity depends on the synaptic interactions within neuronal networks. We studied the mechanisms underlying evoked transient network oscillation in acute slices of the adolescent rat somatosensory cortex and modeled its underpinning mechanisms. Oscillations were evoked by brief spatially distributed noisy extracellular stimulation, delivered via bipolar electrodes. Evoked transient network oscillation was detected with multi-neuron patch-clamp recordings under different pharmacological conditions. The observed oscillations are in the frequency range of 2-5 Hz and consist of 4-12 mV large, 40-150 ms wide compound synaptic events with rare overlying action potentials. This evoked transient network oscillation is only weakly expressed in the somatosensory cortex and requires increased [K+]o of 6.25 mM and decreased [Ca2+]o of 1.5 mM and [Mg2+]o of 0.5 mM. A peak in the cross-correlation among membrane potential in layers II/III, IV and V neurons reflects the underlying network-driven basis of the evoked transient network oscillation. The initiation of the evoked transient network oscillation is accompanied by an increased [K+]o and can be prevented by the K+ channel blocker quinidine. In addition, a shift of the chloride reversal potential takes place during stimulation, resulting in a depolarizing type A GABA (GABAA) receptor response. Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), N-methyl-D-aspartate (NMDA), or GABA(A) receptors as well as gap junctions prevents evoked transient network oscillation while a reduction of AMPA or GABA(A) receptor desensitization increases its duration and amplitude. The apparent reversal potential of -27 mV of the evoked transient network oscillation, its pharmacological profile, as well as the modeling results suggest a mixed contribution of glutamatergic, excitatory GABAergic, and gap junctional conductances in initiation and maintenance of this oscillatory activity. With these properties, evoked transient network oscillation resembles epileptic afterdischarges more than any other form of physiological or pathophysiological neocortical oscillatory activity.

A Novel Implantable Hearing System with Direct Acoustic Cochlear Stimulation

A new implantable hearing system, the direct acoustic cochlear stimulator (DACS) is presented. This system is based on the principle of a power-driven stapes prosthesis and intended for the treatment of severe mixed hearing loss due to advanced otosclerosis. It consists of an implantable electromagnetic transducer, which transfers acoustic energy directly to the inner ear, and an audio processor worn externally behind the implanted ear. The device is implanted using a specially developed retromeatal microsurgical approach. After removal of the stapes, a conventional stapes prosthesis is attached to the transducer and placed in the oval window to allow direct acoustical coupling to the perilymph of the inner ear. In order to restore the natural sound transmission of the ossicular chain, a second stapes prosthesis is placed in parallel to the first one into the oval window and attached to the patient's own incus, as in a conventional stapedectomy. Four patients were implanted with an investigational DACS device. The hearing threshold of the implanted ears before implantation ranged from 78 to 101 dB (air conduction, pure tone average, 0.5-4 kHz) with air-bone gaps of 33-44 dB in the same frequency range. Postoperatively, substantial improvements in sound field thresholds, speech intelligibility as well as in the subjective assessment of everyday situations were found in all patients. Two years after the implantations, monosyllabic word recognition scores in quiet at 75 dB improved by 45-100 percent points when using the DACS. Furthermore, hearing thresholds were already improved by the second stapes prosthesis alone by 14-28 dB (pure tone average 0.5-4 kHz, DACS switched off). No device-related serious medical complications occurred and all patients have continued to use their device on a daily basis for over 2 years. Copyright (c) 2008 S. Karger AG, Basel.

Preference polymorphism for coloration but no speciation in a population of Lake Victoria cichlids

Female mating preference based on male nuptial coloration has been suggested to be an important source of diversifying selection in the radiation of Lake Victoria cichlid fish. Initial variation in female preference is a prerequisite for diversifying selection; however, it is rarely studied in natural populations. In clear water areas of Lake Victoria, the sibling species Pundamilia pundamilia with blue males and Pundamilia nyererei with red males coexist, intermediate phenotypes are rare, and most females have species-assortative mating preferences. Here, we study a population of Pundamilia that inhabits turbid water where male coloration is variable from reddish to blue with most males intermediate. We investigated male phenotype distribution and female mating preferences. Male phenotype was unimodally distributed with a mode on intermediate color in 1 year and more blue-shifted in 2 other years. In mate choice experiments with females of the turbid water population and males from a clearer water population, we found females with a significant and consistent preference for P. pundamilia (blue) males, females with such preferences for P. nyererei (red) males, and many females without a preference. Hence, female mating preferences in this population could cause disruptive selection on male coloration that is probably constrained by the low signal transduction of the turbid water environment. We suggest that if environmental signal transduction was improved and the preference/color polymorphism was stabilized by negative frequency-dependent selection, divergent sexual selection might separate the 2 morphs into reproductively isolated species resembling the clear water species P. pundamilia and P. nyererei.