Tinnitus is associated with increased extracellular matrix density in the auditory cortex of Mongolian gerbils.

Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex.

[The Erlangen model of tinnitus development-New perspective and treatment strategy].

Background: About one sixth of the population of western industrialized nations suffers from chronic, subjective tinnitus, causing socioeconomic treatment and follow-up costs of almost 22 billion euros per year in Germany alone. According to the prevailing view, tinnitus develops as a consequence of a maladaptive neurophysiological process in the brain triggered by hearing loss.

Objectives: The Erlangen model of tinnitus development presented here is intended to propose a comprehensive neurophysiological explanation for the initial occurrence of the phantom sound after hearing loss.

Predictive coding and stochastic resonance as fundamental principles of auditory phantom perception.

Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus-as the prime example of auditory phantom perception-we review recent work at the intersection of artificial intelligence, psychology and neuroscience.

Extracting continuous sleep depth from EEG data without machine learning.

The human sleep-cycle has been divided into discrete sleep stages that can be recognized in electroencephalographic (EEG) and other bio-signals by trained specialists or machine learning systems. It is however unclear whether these human-defined stages can be re-discovered with unsupervised methods of data analysis, using only a minimal amount of generic pre-processing. Based on EEG data, recorded overnight from sleeping human subjects, we investigate the degree of clustering of the sleep stages using the General Discrimination Value as a quantitative measure of class separability.

Is phase locking crucial to improve hearing thresholds in tinnitus patients?

Temporal processing of auditory data plays a crucial role in our proposed model of tinnitus development through stochastic resonance (SR). The model assumes a physiological mechanism optimizing auditory information transmission (as quantified by autocorrelation [AC] analysis) into the brain by adding the optimal amount of neuronal noise to otherwise subthreshold signals. We hypothesize that this takes place at the second synapse of the auditory pathway in the dorsal cochlear nucleus (DCN).

Behavioral Assessment of Zwicker Tone Percepts in Gerbils.

The Zwicker tone illusion - an auditory phantom percept after hearing a notched noise stimulus - can serve as an interesting model for acute tinnitus. Recent mechanistic models suggest that the underlying neural mechanisms of both percepts are similar. To date it is not clear if animals do perceive the Zwicker tone, as up to now no behavioral paradigms are available to objectively assess the presence of this phantom percept.

Classification at the accuracy limit: facing the problem of data ambiguity.

Data classification, the process of analyzing data and organizing it into categories or clusters, is a fundamental computing task of natural and artificial information processing systems. Both supervised classification and unsupervised clustering work best when the input vectors are distributed over the data space in a highly non-uniform way. These tasks become however challenging in weakly structured data sets, where a significant fraction of data points is located in between the regions of high point density.

Estimation of Tinnitus-Related Socioeconomic Costs in Germany.

Despite the high prevalence of tinnitus in Germany of nearly 12% of the general population, there have been no systematic studies on the socioeconomic costs for German society caused by tinnitus so far. Here we analyzed data from 258 chronic tinnitus patients-namely tinnitus severity and health utility index (HUI)-and correlated them with their tinnitus-related public health care costs, private expenses, and economic loss due to their tinnitus percept as assessed by questionnaires. We found correlations of the HUI with health care costs and calculated the mean socioeconomic costs per tinnitus patient in Germany.

Preventive Effects of Ginkgo-Extract EGb 761 on Noise Trauma-Induced Cochlear Synaptopathy.

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea.

Spectrally Matched Near-Threshold Noise for Subjective Tinnitus Loudness Attenuation Based on Stochastic Resonance.

Recently, we proposed a model of tinnitus development based on a physiological mechanism of permanent optimization of information transfer from the auditory periphery to the central nervous system by means of neuronal stochastic resonance utilizing neuronal noise to be added to the cochlear input, thereby improving hearing thresholds. In this view, tinnitus is a byproduct of this added neuronal activity. Interestingly, in healthy subjects auditory thresholds can also be improved by adding external, near-threshold acoustic noise.

Phantom-based prospective analysis of the accuracy of photo registration technology in electromagnetic navigation of the frontal skull base.

Objective: This prospective study compared the accuracy of two different company-specific registration methods (Fiagon GmbH, Hennigsdorf, Germany) in the electromagnetic navigation of the frontal skull base. A newly developed photo registration technology (Fiagon tracey©) promises an increase in accuracy and user-friendliness, but there is no phantom-based prospective study comparing the new method with the classic approach of tactile surface registration.

Materials And Methods: A phantom skull was prepared with 27 markers in the sagittal, axial and coronary planes, and their reference coordinates were determined using a navigational CT (low dose, slice 0.

A Founder Mutation in Presents with Tubular Proteinuria and Deafness.

Background: The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis.

Salicylate-Induced Changes in Hearing Thresholds in Mongolian Gerbils Are Correlated With Tinnitus Frequency but Not With Tinnitus Strength.

Tinnitus is an auditory phantom percept without external sound sources. Despite the high prevalence and tinnitus-associated distress of affected patients, the pathophysiology of tinnitus remains largely unknown, making prevention and treatments difficult to develop. In order to elucidate the pathophysiology of tinnitus, animal models are used where tinnitus is induced either permanently by noise trauma or transiently by the application of salicylate.

Simulated transient hearing loss improves auditory sensitivity.

Recently, it was proposed that a processing principle called adaptive stochastic resonance plays a major role in the auditory system, and serves to maintain optimal sensitivity even to highly variable sound pressure levels. As a side effect, in case of reduced auditory input, such as permanent hearing loss or frequency specific deprivation, this mechanism may eventually lead to the perception of phantom sounds like tinnitus or the Zwicker tone illusion. Using computational modeling, the biological plausibility of this processing principle was already demonstrated.

Tinnitus development is associated with synaptopathy of inner hair cells in Mongolian gerbils.

Human hearing loss (HL) is often accompanied by comorbidities like tinnitus, which is affecting up to 15% of the adult population. Rodent animal studies could show that tinnitus may not only be a result of apparent HL due to cochlear hair cell damage but can also be a consequence of synaptopathy at the inner hair cells (IHCs) already induced by moderate sound traumata. Here, we investigate synaptopathy previously shown in mice in our animal model, the Mongolian gerbil, and relate it to behavioral signs of tinnitus.

The stochastic resonance model of auditory perception: A unified explanation of tinnitus development, Zwicker tone illusion, and residual inhibition.

Stochastic resonance (SR) has been proposed to play a major role in auditory perception, and to maintain optimal information transmission from the cochlea to the auditory system. By this, the auditory system could adapt to changes of the auditory input at second or even sub-second timescales. In case of reduced auditory input, somatosensory projections to the dorsal cochlear nucleus would be disinhibited in order to improve hearing thresholds by means of SR.

Acute and Long-Term Circuit-Level Effects in the Auditory Cortex After Sound Trauma.

Harmful environmental sounds are a prevailing source of chronic hearing impairments, including noise induced hearing loss, hyperacusis, or tinnitus. How these symptoms are related to pathophysiological damage to the sensory receptor epithelia and its effects along the auditory pathway, have been documented in numerous studies. An open question concerns the temporal evolution of maladaptive changes after damage and their manifestation in the balance of thalamocortical and corticocortical input to the auditory cortex (ACx).

[Reducing tinnitus intensity : Pilot study to attenuate tonal tinnitus using individually spectrally optimized near-threshold noise].

Background: Around 15% of the general population is affected by tinnitus, but no real cure exists despite intensive research. Based on our recent causal model for tinnitus development, we here test a new treatment aimed at counteracting the perception. This treatment is based on the stochastic resonance phenomenon at specific auditory system synapses that is induced by externally presented near-threshold noise.

β-Secretase BACE1 Is Required for Normal Cochlear Function.

Cleavage of amyloid precursor protein (APP) by β-secretase BACE1 initiates the production and accumulation of neurotoxic amyloid-β peptides, which is widely considered an essential pathogenic mechanism in Alzheimer's disease (AD). Here, we report that BACE1 is essential for normal auditory function. Compared with wild-type littermates, BACE1 mice of either sex exhibit significant hearing deficits, as indicated by increased thresholds and reduced amplitudes in auditory brainstem responses (ABRs) and decreased distortion product otoacoustic emissions (DPOAEs).

Open(G)PIAS: An Open-Source Solution for the Construction of a High-Precision Acoustic Startle Response Setup for Tinnitus Screening and Threshold Estimation in Rodents.

The modulation of the acoustic startle reflex (ASR) by a pre-stimulus called pre-pulse inhibition (PPI, for gap of silence pre-stimulus: GPIAS) is a versatile tool to, e.g., estimate hearing thresholds or identify subjective tinnitus percepts in rodents.

Objective Estimation of Sensory Thresholds Based on Neurophysiological Parameters.

Reliable determination of sensory thresholds is the holy grail of signal detection theory. However, there exists no assumption-independent gold standard for the estimation of thresholds based on neurophysiological parameters, although a reliable estimation method is crucial for both scientific investigations and clinical diagnosis. Whenever it is impossible to communicate with the subjects, as in studies with animals or neonates, thresholds have to be derived from neural recordings or by indirect behavioral tests.

[Models of tinnitus development : From cochlea to cortex].

The development of subjective tinnitus is still not mechanistically understood and existing models are controversially discussed. In this overview, the authors discuss three of the main models, all of which propose damage to the cochlea as the initial step in tinnitus development. Based on these models, a possible manifestation of tinnitus-related neuronal activity at the perceptually relevant level of the auditory pathway, the auditory cortex, is presented.

Analysis of Multichannel EEG Patterns During Human Sleep: A Novel Approach.

Classic visual sleep stage scoring is based on electroencephalogram (EEG) frequency band analysis of 30 s epochs and is commonly performed by highly trained medical sleep specialists using additional information from submental EMG and eye movements electrooculogram (EOG). In this study, we provide the proof-of-principle in 40 subjects that sleep stages can be consistently differentiated solely on the basis of spatial 3-channel EEG patterns based on root-mean-square (RMS) amplitudes. The polysomnographic 3-channel EEG data are pre-processed by RMS averaging over intervals of 30 s leading to spatial cortical activity patterns represented by 3-dimensional vectors.