BACKGROUND: Nonrechargeable deep brain stimulation impulse generators (IGs) with low or empty battery status require surgical IG exchange several years after initial implantation. The aim of this study was to investigate complication rates after IG exchange surgery and identify risk factors. METHODS: We retrospectively analyzed complications following IG exchange surgery from 2008 to 2015 in our department. Medical records of all patients who underwent IG exchange surgery were systematically reviewed. The shortest follow-up time was 19 months. RESULTS: From 2008 to 2015, 438 IGs were exchanged in 319 patients. Overall complication rate was 8.90\%. Infection developed in 12 patients (2.74\%). Six patients (1.37\%) experienced local wound erosions. Hardware malfunctions were present in 11 patients (2.51\%), and local hemorrhage was observed in 3 cases (0.68\%). Repeated fixation of the IG was required in 2 patients (0.46\%). Traction of the connecting cables necessitated surgical revision in 2 patients (0.46\%). In 2 cases (0.46\%), the IG was placed abdominally or exchanged for a smaller device owing to patient discomfort resulting from the initial positioning. One 80-year-old patient (0.23\%) had severely worsening heart failure and died 4 days after IG exchange surgery. CONCLUSIONS: IG exchange surgery, although often considered a minor surgery, was associated with a complication rate of approximately 9\% in our center. Patients and physicians should understand the complication rates associated with IG exchange surgery because this information might facilitate selection of a rechargeable IG.

Previous studies demonstrated the influence of the post-learning period on procedural motor memory consolidation. In an early period after the acquisition, motor skills are vulnerable to modifications during wakefulness. Indeed, specific interventions such as world-list learning within this early phase of motor memory consolidation seem to enhance motor performance as an indicator for successful consolidation. This finding highlights the idea that manipulations of procedural and declarative memory systems during the early phase of memory consolidation over wakefulness may influence off-line consolidation. Using functional magnetic resonance imaging (fMRI) during initial motor sequence learning and motor sequence recall, we indirectly assess the influence of a secondary task taken place in the early phase of memory consolidation. All participants were scanned using fMRI during the learning phase of a serial reaction time task (SRTT) at 8 a.m.. Afterwards, they were randomly assigned to one of five conditions. One group performed a declarative verbal, one a declarative nonverbal learning task. Two groups worked on attention tasks. A control group passed a resting condition. Participants stayed awake the whole day and performed the SRTT in the MRI scanner 12h later at 8 p.m.. At the behavioral level, the analysis of the reaction times failed to show a significant group difference. The primary analysis assessing fMRI data based on the contrast (sequence - random) between learning and retrieval also did not show any significant group differences. Therefore, our main analysis do not support the hypothesis that a secondary task influences the retrieval of the SRTT. In a more liberal fMRI analysis, we compared only the sequence blocks of the SRTT from learning to recall. BOLD signal decreased in the ipsilateral cerebellum and the supplementary motor area solely in the verbal learning group. Although our primary analysis failed to show significant changes between our groups, results of the secondary analysis could be an indication for a beneficial effect of the verbal declarative task in the early post-learning phase. A nonverbal learning task did not affect the activation within the motor network. Further studies are needed to replicate this finding and to assess the usefulness of this manipulation.

Background Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. Methods We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1: 1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Findings Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39\% (-363.3 mg/day {[}SE 41.8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21\% (245.8 mg/day {[}40.4]) in those assigned medical therapy alone (p<0.0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0.65 points {[}SE 0.15]) and did not change with medical therapy alone (-0.02 points {[}0.15]); the between-group difference in change from baseline was significant (p=0.0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1.26 points {[}SE 0.35]) and had increased with medical therapy alone (1.12 points {[}0.35]); the between-group difference was significant (p<0.0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. Interpretation In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications.

Purpose: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen cognitive functions and recent studies have shown alterations in the brains of patients with neuropathic pain, it may be possible that these drugs have neurotoxic effects. Methods: Rat clonal PC12 pheochromocytoma (autonomic) and primary sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed for this study. To mimic neuronal damage, cells were exposed to cytotoxins using either hydrogen peroxide (H2O2) or vincristine. Results: No direct cytotoxic effects were observed after incubating PC12 cells for 24 hours with increasing concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a 7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12 and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the cytotoxic effects of H2O2 or vincristine after incubation for 24 hours and 7 days, respectively. Cell morphology and integrity of the cytoskeleton assessed by employing immunostaining of cytoskeletal proteins (alpha-tubulin, neurofilament L) remained intact and were not altered by gabapentinoids. Conclusion: Based on these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic (PC12) and sensory DRG cells, even when cells are preinjured. These results are of high clinical relevance, as it seems unlikely that the morphological changes recently observed in the brains of neuropathic pain patients are caused or worsened by gabapentinoids.

The paper describes a system for automatic speech recognition (ASR) that is benchmarked with data of the 3rd CHiME challenge, a dataset comprising distant microphone recordings of noisy acoustic scenes in public environments. The proposed ASR system employs various methods to increase recognition accuracy and noise robustness. Two different multi-channel speech enhancement techniques are used to eliminate interfering sounds in the audio stream. One speech enhancement method aims at separating the target speaker's voice from background sources based on non-negative matrix factorization (NMF) using variational Bayesian (VB) inference to estimate NMF parameters. The second technique is based on a time-varying minimum variance distortionless response (MVDR) beamformer that uses spatial information to suppress sound signals not arriving from a desired direction. Prior to speech enhancement, a microphone channel failure detector is applied that is based on cross-comparing channels using a modulation-spectral representation of the speech signal. ASR feature extraction employs the amplitude modulation filter bank (AMFB) that implicates prior information of speech to analyze its temporal dynamics. AMFBs outperform the commonly used frame splicing technique of filter bank features in conjunction with a deep neural network (DNN) based ASR system, which denotes an equivalent data-driven approach to extract modulation-spectral information. In addition, features are speaker adapted, a recurrent neural network (RNN) is employed for language modeling, and hypotheses of different ASR systems are combined to further enhance the recognition accuracy. The proposed ASR system achieves an absolute word error rate (WER) of 5.67\% on the real evaluation test data, which is 0.16\% lower compared to the best score reported within the 3rd CHiME challenge. (C) 2017 Elsevier Ltd. All rights reserved.

This paper evaluates neural network (NN) based systems and compares them to Gaussian mixture model (GMM) and hidden Markov model (HMM) approaches for acoustic scene classification (SC) and polyphonic acoustic event detection (AED) that are applied to data of the ``Detection and Classification of Acoustic Scenes and Events 2016{''} (DCASE' 16) challenge, task 1 and task 3, respectively. For both tasks, the use of deep neural networks (DNNs) and features based on an amplitude modulation filterbank and a Gabor filterbank (GFB) are evaluated and compared to standard approaches. For SC, additionally a time-delay NN approach is proposed that enables analysis of long contextual information similar to recurrent NNs but with training efforts comparable to conventional DNNs. The SC system proposed for task 1 of the DCASE' 16 challenge attains a recognition accuracy of 77.5\%, which is 5.6\% higher compared to the DCASE' 16 baseline system. For the AED task, DNNs are adopted in tandem and hybrid approaches, i.e., as part of HMM-based systems. These systems are evaluated for the polyphonic data of task 3 from the DCASE' 16 challenge. Several strategies to address the issue of polyphony are considered. It is shown that DNN-based systems perform less accurate than the traditional systems for this task. Best results are achieved using GFB features in combination with a multiclass GMM-HMM back end.

Gabor filters have long been proposed as models for spectro-temporal receptive fields (STRFs), with their specific spectral and temporal rate of modulation qualitatively replicating characteristics of STRF filters estimated from responses to auditory stimuli in physiological data. The present study builds on the Gabor-STRF model by proposing a methodology to quantitatively decompose STRFs into a set of optimally matched Gabor filters through matching pursuit, and by quantitatively evaluating spectral and temporal characteristics of STRFs in terms of the derived optimal Gabor-parameters. To summarize a neuron's spectro-temporal characteristics, we introduce a measure for the ``diagonality,{''} i.e., the extent to which an STRF exhibits spectro-temporal transients which cannot be factorized into a product of a spectral and a temporal modulation. With this methodology, it is shown that approximately half of 52 analyzed zebra finch STRFs can each be well approximated by a single Gabor or a linear combination of two Gabor filters. Moreover, the dominant Gabor functions tend to be oriented either in the spectral or in the temporal direction, with truly ``diagonal{''} Gabor functions rarely being necessary for reconstruction of an STRF's main characteristics. As a toy example for the applicability of STRF and Gabor-STRF filters to auditory detection tasks, we use STRF filters as features in an automatic event detection task and compare them to idealized Gabor filters and mel-frequency cepstral coefficients (MFCCs). STRFs classify a set of six everyday sounds with an accuracy similar to reference Gabor features (94\% recognition rate). Spectro-temporal STRF and Gabor features outperform reference spectral MFCCs in quiet and in low noise conditions (down to 0 dB signal to noise ratio).

Background: We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor. Methods: Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (>= 48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications. Results: There was a 21.6\% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5\%) in the subgroup of patients with an additional long-term follow-up (8 of 17). The latency of symptoms on standing significantly improved, both in the shortterm (P = 0.001) and in the long-term (P = 0.018). Three patients obtained no/minimal benefit from the procedure. Conclusions: Deep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. (C) 2017 International

Background and Purpose: This study investigates the prevalence of delirium in acute stroke patients on a primary stroke unit (SU) analyzing associated risk factors and clinical outcomes. Method: Prospective, 4-month observational study from 2015 to 2016 on patients aged >= 18years with stroke at a German university hospital's SU. The presence of delirium as first outcome was rated at three times daily using the Confusion Assessment Method (CAM). Secondary outcome measures were duration of delirium, rehabilitation in SU, length of stay in SU and hospital, complications, and mortality. Significant risk factors were used to conduct a confounder-matched case-control analysis. Results: 309 patients were included. The overall prevalence of delirium was 10.7\% (33 patients) mostly on the first and second hospital day. Duration of delirium on SU was in median 1.0 day (Interquartile range: 0.3-2days). In 39.4\% of patients delirium was present in a short time interval (<= 8 hr) and in 24\% of patients delirium was diagnosed during nightshifts exclusively. Significant risk factors for delirium were dementia, age >= 72 years, severe neurological disability on admission, and increased C-reactive protein on admission. The case-control analysis showed that delirious patients had more complications and a trend toward a worse rehabilitation. Conclusions: These results underline the importance of delirium screening in stroke patients specifically during the night. Since even short delirious episodes are associated with more complications and increased disability, future studies are needed to find delirium prevention strategies.

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 +/- 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology. (C) 2016 Elsevier Ltd. All rights reserved.

Background: The introduction of deep brain stimulation (DBS) about 25 years ago provided one of the major breakthroughs in the treatment of Parkinson's disease (PD). However, a high percentage of patients are reluctant to undergo DBS. Previous research revealed that the critical step on the patient's path to DBS is the decision whether to undergo further diagnostic assessment for surgery at a specialized DBS-center. The aims of the current study were to evaluate how effective the combination of an outpatient DBS screening tool, STIMULUS, with specially developed educational material was to enhance patient education on DBS and to identify motivational aspects which influenced the patients' willingness to undergo further assessment. Methods: In total, 264 patients were identified as appropriate candidates for DBS by general neurologists using the electronic preselection tool STIMULUS. Patient-centered information material was designed and handed out to support education on DBS. Further, several clinical characteristics and details of the patient counseling were documented. Refusal or consent to show up at a DBS center was registered over the following 16 months. Results: 114 (43.2\%) patients preselected as eligible for DBS (STIMULUS Score >= 6) agreed to show up at a specialized DBS center to undergo further diagnostic assessment. The patients' ages, PD classification as an akinetic-rigid type and the talks' topics side-effects of dopaminergic medication and the optimal time frame had a significant influence on the patients' decisions. Conclusions: The combination of preselection tools as STIMULUS with comprehensive information material is effective to increase DBS-acceptance rate in PD patients. Important topics of the information about DBS cover the optimal time frame for DBS surgery, the side-effects of dopaminergic medication as well as side-effects and complications of DBS surgery.

Background: Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease (PD). Objective: To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients. Methods: Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery. Results: PD patients had a significant lower global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn \& Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables. Conclusions: PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced.

While subjective reports provide a direct measure of perception, their validity is not self-evident. Here, the authors tested three possible biasing effects on perceptual reports in the auditory streaming paradigm: errors due to imperfect understanding of the instructions, voluntary perceptual biasing, and susceptibility to implicit expectations. (1) Analysis of the responses to catch trials separately promoting each of the possible percepts allowed the authors to exclude participants who likely have not fully understood the instructions. (2) Explicit biasing instructions led to markedly different behavior than the conventional neutral-instruction condition, suggesting that listeners did not voluntarily bias their perception in a systematic way under the neutral instructions. Comparison with a random response condition further supported this conclusion. (3) No significant relationship was found between social desirability, a scale-based measure of susceptibility to implicit social expectations, and any of the perceptual measures extracted from the subjective reports. This suggests that listeners did not significantly bias their perceptual reports due to possible implicit expectations present in the experimental context. In sum, these results suggest that valid perceptual data can be obtained from subjective reports in the auditory streaming paradigm

Multi-stability refers to the phenomenon of perception stochastically switching between possible interpretations of an unchanging stimulus. Despite considerable variability, individuals show stable idiosyncratic patterns of switching between alternative perceptions in the auditory streaming paradigm. We explored correlates of the individual switching patterns with executive functions, personality traits, and creativity. The main dimensions on which individual switching patterns differed from each other were identified using multidimensional scaling. Individuals with high scores on the dimension explaining the largest portion of the inter-individual variance switched more often between the alternative perceptions than those with low scores. They also perceived the most unusual interpretation more often, and experienced all perceptual alternatives with a shorter delay from stimulus onset. The ego-resiliency personality trait, which reflects a tendency for adaptive flexibility and experience seeking, was significantly positively related to this dimension. Taking these results together we suggest that this dimension may reflect the individual's tendency for exploring the auditory environment. Executive functions were significantly related to some of the variables describing global properties of the switching patterns, such as the average number of switches. Thus individual patterns of perceptual switching in the auditory streaming paradigm are related to some personality traits and executive functions

Cochlear implant (CI) users show higher auditory-evoked activations in visual cortex and higher visual-evoked activation in auditory cortex compared to normal hearing (NH) controls, reflecting functional reorganization of both visual and auditory modalities. Visual-evoked activation in auditory cortex is a maladaptive functional reorganization whereas auditory-evoked activation in visual cortex is beneficial for speech recognition in CI users. We investigated their joint influence on CI users' speech recognition, by testing 20 postlingually deafened CI users and 20 NH controls with functional near-infrared spectroscopy (fNIRS). Optodes were placed over occipital and temporal areas to measure visual and auditory responses when presenting visual checkerboard and auditory word stimuli. Higher cross-modal activations were confirmed in both auditory and visual cortex for CI users compared to NH controls, demonstrating that functional reorganization of both auditory and visual cortex can be identified with fNIRS. Additionally, the combined reorganization of auditory and visual cortex was found to be associated with speech recognition performance. Speech performance was good as long as the beneficial auditory-evoked activation in visual cortex was higher than the visual-evoked activation in the auditory cortex. These results indicate the importance of considering cross-modal activations in both visual and auditory cortex for potential clinical outcome estimation

High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear.To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality.The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period.Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance.The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections.Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure.Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation.clinicaltrials.gov Identifier: NCT00832039

Surface plasmon resonance (SPR) spectroscopy is widely used to probe interactions involving biological macromolecules by detecting changes in the refractive index in a metal/dielectric interface following the dynamic formation of a molecular complex. In the last years SPR-based experimental approaches were developed to monitor conformational changes induced by the binding of small analytes to proteins coupled to the surface of commercially available sensor chips. A significant contribution to our understanding of the phenomenon came from the study of several Ca2+-sensor proteins operating in diverse cellular scenarios, in which the conformational switch is triggered by specific Ca2+ signals. Structural and physicochemical analyses demonstrated that the SPR signal not only depends on the change in protein size upon Ca2+-binding but likely originates from variations in the hydration shell structure. The resulting changes in the dielectric properties of water or of the protein-water interface eventually reflect different crowding conditions on the SPR sensor chip, which mimic the cellular environment. SPR could hence be used to monitor conformational transitions in proteins, especially when a significant variation in the hydrophobicity of the solvent-exposed protein surface occurs, thus leading to changes in the dielectric milieu of the whole sensor chip surface. We review recent work in which SPR has been successfully employed to provide a fingerprint of the conformational change dynamics in proteins under native and altered conditions, which include posttranslational modifications, co-presence of competing analytes and point mutations of single amino acids associated to genetic diseases

Myristoylation of most neuronal calcium sensor proteins, a group of EF-hand calcium-binding proteins mainly expressed in neuronal tissue, can have a strong impact on protein dynamics and functional properties. Intracellular oscillations of the free Ca(2+) concentration can trigger conformational changes in Ca(2+) sensors. The position and possible movements of the myristoyl group in the photoreceptor cell-specific Ca(2+) sensor GCAP2 are not well-defined but appear to be different from those of the highly homologous cognate GCAP1. We designed and applied a new group of diaminoterephthalate-derived fluorescent probes to label GCAP2 at a covalently attached 12-azido-dodecanoic acid (a myristoyl substitute) and at cysteine residues in critical positions. Fluorescence emission of dye-labeled GCAP2 decreased when going from low (10(-9) M) to high [Ca(2+)] (10(-3) M), reaching a half-maximal effect of fluorescence emission at 0.44 ± 0.07 μM. The modified acyl group can therefore monitor changes in the protein conformation during binding and dissociation of Ca(2+) in the physiological range of free [Ca(2+)]. However, fluorescence quenching studies showed that the dye-acyl chain was shielded from the quencher by an adjacent polypeptide region. Further probing three cysteine positions (C35, C111, and C131) by dye labeling revealed that all positions were also sensitive to a change in [Ca(2+)], but only one (C131) was sensitive to a change in [Mg(2+)]. We suggest a scenario during illumination of the photoreceptor cell in which Ca(2+) dissociates first from low and medium affinity binding sites. These steps are sensed by dyes in cysteines at positions 35 and 111. Release of Ca(2+) from high affinity sites is sensed by regions adjacent to the dye-labeled fatty acid and involves the critical conformational change leading to activating guanylate cyclase

The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells

As a step towards the realization of neuro-prosthetics for vision restoration, we follow an electrophysiological patch-clamp approach to study the fundamental photoelectrical stimulation mechanism of neuronal model cells by an organic semiconductor-electrolyte interface. Our photoactive layer consisting of an anilino-squaraine donor blended with a fullerene acceptor is supporting the growth of the neuronal model cell line (N2A cells) without an adhesion layer on it, and is not impairing cell viability. The transient photocurrent signal upon illumination from the semiconductor-electrolyte layer is able to trigger a passive response of the neuronal cells under physiological conditions via a capacitive coupling mechanism. We study the dynamics of the capacitive transmembrane currents by patch-clamp recordings and compare them to the dynamics of the photocurrent signal and its spectral responsivity. Furthermore, we characterize the morphology of the semiconductor-electrolyte interface by atomic force microscopy, and study the stability of the interface in dark and under illuminated conditions

Heterojunction solar cells based on colloidal nanocrystals (NCs) have shown remarkable improvements in performance in the last decade, but this progress is limited to merely two materials, PbS and PbSe. However, solar cells based on other material systems such as copper-based compounds show lower power conversion efficiencies and much less effort has been made to develop a better understanding of factors limiting their performance. Here, we study charge carrier loss mechanisms in solution-processed CuInS2/ZnO NC solar cells by combining steady-state measurements with transient photocurrent and photovoltage measurements. We demonstrate the presence of an extraction barrier at the CuInS2/ZnO interface, which can be reduced upon illumination with UV light. However, trap-assisted recombination in the CuInS2 layer is shown to be the dominant decay process in these devices

We report a drastic increase of the damping time of plasmonic eigenmodes in resonant bull's eye (BE) nanoresonators to more than 35 fs. This is achieved by tailoring the groove depth of the resonator and by coupling the confined plasmonic field in the aperture to an extended resonator mode such that spatial coherence is preserved over distances of more than 10 μm. Experimentally, this is demonstrated by probing the plasmon dynamics at the field level using broadband spectral interferometry. The nanoresonator allows us to efficiently concentrate the incident field inside the central aperture of the BE and to tailor its local optical nonlinearity by varying the aperture geometry. By replacing the central circular hole with an annular ring structure, we obtain 50-times higher second harmonic generation efficiency, allowing us to demonstrate the efficient concentration of long-lived plasmonic modes inside nanoapertures by interferometric frequency-resolved autocorrelation. Such a light concentration in a nanoresonator with high quality factor has high potential for sensing and coherent control of light-matter interactions on the nanoscale

Saccadic reaction times from a focused-attention task with a visual target and an acoustic nontarget support the hypothesis that the amount of saccadic facilitation in the presence of a nontarget increases with the prior knowledge of alignment with the target across different blocks of trials. The time-window-of-integration model can account for the size of the effect by having window size depend on the prior knowledge of alignment. Some efforts to identify the neural correlates of the effect are discussed

Understanding the function of modulatory interneuron networks is a major challenge, because such networks typically operate over long spatial scales and involve many neurons of different types. Here, we use an indirect electrical imaging method to reveal the function of a spatially extended, recurrent retinal circuit composed of two cell types. This recurrent circuit produces peripheral response suppression of early visual signals in the primate magnocellular visual pathway. We identify a type of polyaxonal amacrine cell physiologically via its distinctive electrical signature, revealed by electrical coupling with ON parasol retinal ganglion cells recorded using a large-scale multi-electrode array. Coupling causes the amacrine cells to fire spikes that propagate radially over long distances, producing GABA-ergic inhibition of other ON parasol cells recorded near the amacrine cell axonal projections. We propose and test a model for the function of this amacrine cell type, in which the extra-classical receptive field of ON parasol cells is formed by reciprocal inhibition from other ON parasol cells in the periphery, via the electrically coupled amacrine cell network

In a natural environment, sensory systems are faced with ever-changing stimuli that can occur, disappear or change their properties at any time. For the animal to react adequately the sensory systems must be able to detect changes in external stimuli based on its neuronal responses. Since the nervous system has no prior knowledge of the stimulus timing, changes in stimulus need to be inferred from the changes in neuronal activity, in particular increase or decrease of the spike rate, its variability, and shifted response latencies. From a mathematical point of view, this problem can be rephrased as detecting changes of statistical properties in a time series. In neuroscience, the CUSUM (cumulative sum) method has been applied to recorded neuronal responses for detecting a single stimulus change. Here, we investigate the applicability of the CUSUM approach for detecting single as well as multiple stimulus changes that induce increases or decreases in neuronal activity. Like the nervous system, our algorithm relies exclusively on previous neuronal population activities, without using knowledge about the timing or number of external stimulus changes. We apply our change point detection methods to experimental data obtained by multi-electrode recordings from turtle retinal ganglion cells, which react to changes in light stimulation with a range of typical neuronal activity patterns. We systematically examine how variations of mathematical assumptions (Poisson, Gaussian, and Gamma distributions) used for the algorithms may affect the detection of an unknown number of stimulus changes in our data and compare these CUSUM methods with the standard Rate Change method. Our results suggest which versions of the CUSUM algorithm could be useful for different types of specific data sets

Already in his first report on the discovery of the human EEG in 1929, Berger showed great interest in further elucidating the functional roles of the alpha and beta waves for normal mental activities. Meanwhile, most cognitive processes have been linked to at least one of the traditional frequency bands in the delta, theta, alpha, beta, and gamma range. Although the existing wealth of high-quality correlative EEG data led many researchers to the conviction that brain oscillations subserve various sensory and cognitive processes, a causal role can only be demonstrated by directly modulating such oscillatory signals. In this review, we highlight several methods to selectively modulate neuronal oscillations, including EEG-neurofeedback, rhythmic sensory stimulation, repetitive transcranial magnetic stimulation (rTMS), and transcranial alternating current stimulation (tACS). In particular, we discuss tACS as the most recent technique to directly modulate oscillatory brain activity. Such studies demonstrating the effectiveness of tACS comprise reports on purely behavioral or purely electrophysiological effects, on combination of behavioral effects with offline EEG measurements or on simultaneous (online) tACS-EEG recordings. Whereas most tACS studies are designed to modulate ongoing rhythmic brain activity at a specific frequency, recent evidence suggests that tACS may also modulate cross-frequency interactions. Taken together, the modulation of neuronal oscillations allows to demonstrate causal links between brain oscillations and cognitive processes and to obtain important insights into human brain function

Transcranial alternating current stimulation (tACS) has been repeatedly demonstrated to increase power of endogenous brain oscillations in the range of the stimulated frequency after stimulation. In the alpha band this aftereffect has been shown to persist for at least 30 min. However, in most experiments the aftereffect exceeded the duration of the measurement. Thus, it remains unclear how the effect develops beyond these 30 min and when it decays. The current study aimed to extend existing findings by monitoring the physiological aftereffect of tACS in the alpha range for an extended period of 90 min post-stimulation. To this end participants received either 20 min of tACS or sham stimulation with intensities below their individual sensation threshold at the individual alpha frequency (IAF). Electroencephalogram (EEG) was acquired during 3 min before and 90 min after stimulation. Subjects performed a visual vigilance task during the whole measurement. While the enhanced power in the individual alpha band did not return back to pre-stimulation baseline in the stimulation group, the difference between stimulation and sham diminishes after 70 min due to a natural alpha increase of the sham group

Granger causality is a statistical concept devised to reconstruct and quantify predictive information flow between stochastic processes. Although the general concept can be formulated model-free it is often considered in the framework of linear stochastic processes. Here we show how local linear model descriptions can be employed to extend Granger causality into the realm of nonlinear systems. This novel treatment results in maps that resolve Granger causality in regions of state space. Through examples we provide a proof of concept and illustrate the utility of these maps. Moreover, by integration we convert the local Granger causality into a global measure that yields a consistent picture for a global Ornstein-Uhlenbeck process. Finally, we recover invariance transformations known from the theory of autoregressive processes

Sarcopenia and osteopenia/osteoporosis show a high prevalence in old age and incur a high risk for falls, fractures, and further functional decline. Physical performance and bone metabolism in patients suffering from the so-called osteosarcopenia-the combination of sarcopenia and osteopenia-are currently still unknown.This study investigates physical performance and bone metabolism in osteosarcopenic, prefrail, community-dwelling older adults.68 prefrail adults between 65 and 94 years were assigned to four groups according to mean DXA results: osteosarcopenic [low T-score and low appendicular lean mass (aLM)], sarcopenic (low aLM), osteopenic (low T-score), and controls. Multiple linear regression analysis, adjusted for age, gender, physical activity, and 25-OH-vitamin D3 serum level, was used to identify the influence of being osteosarcopenic, sarcopenic, or osteopenic on physical performance (hand grip, chair rise test, sit-to-stand power, gait speed, SPPB) and serum markers for increased bone turnover [osteocalcin, β-crosslaps and procollagen type 1 amino-terminal propeptide (P1NP)].Only osteosarcopenic participants showed significantly reduced hand grip strength, increased chair rising time, and STS power time as well as significantly increased bone turnover markers.Due to low physical performance and high bone turnover, older adults with osteosarcopenia have to be regarded as the most at-risk population for fractures and further functional decline.Up-to-date osteoporosis and post-fracture management of older persons should aim at both, bone and muscle

The biosynthetic precursor of redox cofactor F420, 7,8-didemethyl-8-hydroxy-5-deazariboflavin, was prepared in four steps from 6-chlorouracil, 2-chloro-4-hydroxybenzaldehyde and bis-isopropylidene protected D-ribose. The latter aldehyde was transformed to the corresponding protected ribitylamine via the oxime, which was submitted to reduction with LiAlH4. Key advantage compared to previous syntheses is the utilization of a polyol-protective group which allowed the chromatographic purification of a key-intermediate product providing the target compound with high purity

The nocturnal Bogong moth (Agrotis infusa) is an iconic and well-known Australian insect that is also a remarkable nocturnal navigator. Like the Monarch butterflies of North America, Bogong moths make a yearly migration over enormous distances, from southern Queensland, western and northwestern New South Wales (NSW) and western Victoria, to the alpine regions of NSW and Victoria. After emerging from their pupae in early spring, adult Bogong moths embark on a long nocturnal journey towards the Australian Alps, a journey that can take many days or even weeks and cover over 1000 km. Once in the Alps (from the end of September), Bogong moths seek out the shelter of selected and isolated high ridge-top caves and rock crevices (typically at elevations above 1800 m). In hundreds of thousands, moths line the interior walls of these cool alpine caves where they "hibernate" over the summer months (referred to as "estivation"). Towards the end of the summer (February and March), the same individuals that arrived months earlier leave the caves and begin their long return trip to their breeding grounds. Once there, moths mate, lay eggs and die. The moths that hatch in the following spring then repeat the migratory cycle afresh. Despite having had no previous experience of the migratory route, these moths find their way to the Alps and locate their estivation caves that are dotted along the high alpine ridges of southeastern Australia. How naïve moths manage this remarkable migratory feat still remains a mystery, although there are many potential sensory cues along the migratory route that moths might rely on during their journey, including visual, olfactory, mechanical and magnetic cues. Here we review our current knowledge of the Bogong moth, including its natural history, its ecology, its cultural importance to the Australian Aborigines and what we understand about the sensory basis of its long-distance nocturnal migration. From this analysis it becomes clear that the Bogong moth represents a new and very promising model organism for understanding the sensory basis of nocturnal migration in insects

Magnetic compass orientation in night-migratory songbirds is embedded in the visual system and seems to be based on a light-dependent radical pair mechanism. Recent findings suggest that both broadband electromagnetic fields ranging from ~2 kHz to ~9 MHz and narrow-band fields at the so-called Larmor frequency for a free electron in the Earth's magnetic field can disrupt this mechanism. However, due to local magnetic fields generated by nuclear spins, effects specific to the Larmor frequency are difficult to understand considering that the primary sensory molecule should be organic and probably a protein. We therefore constructed a purpose-built laboratory and tested the orientation capabilities of European robins in an electromagnetically silent environment, under the specific influence of four different oscillating narrow-band electromagnetic fields, at the Larmor frequency, double the Larmor frequency, 1.315 MHz or 50 Hz, and in the presence of broadband electromagnetic noise covering the range from ~2 kHz to ~9 MHz. Our results indicated that the magnetic compass orientation of European robins could not be disrupted by any of the relatively strong narrow-band electromagnetic fields employed here, but that the weak broadband field very efficiently disrupted their orientation

Although it has been known for almost half a century that migratory birds can detect the direction of the Earth's magnetic field, the primary sensory mechanism behind this remarkable feat is still unclear. The leading hypothesis centers on radical pairs-magnetically sensitive chemical intermediates formed by photoexcitation of cryptochrome proteins in the retina. Our primary aim here is to explain the chemical and physical aspects of the radical-pair mechanism to biologists and the biological and chemical aspects to physicists. In doing so, we review the current state of knowledge on magnetoreception mechanisms. We dare to hope that this tutorial will stimulate new interdisciplinary experimental and theoretical work that will shed much-needed additional light on this fascinating problem in sensory biology

Migratory birds have a light-dependent magnetic compass, the mechanism of which is thought to involve radical pairs formed photochemically in cryptochrome proteins in the retina. Theoretical descriptions of this compass have thus far been unable to account for the high precision with which birds are able to detect the direction of the Earth's magnetic field. Here we use coherent spin dynamics simulations to explore the behavior of realistic models of cryptochrome-based radical pairs. We show that when the spin coherence persists for longer than a few microseconds, the output of the sensor contains a sharp feature, referred to as a spike. The spike arises from avoided crossings of the quantum mechanical spin energy-levels of radicals formed in cryptochromes. Such a feature could deliver a heading precision sufficient to explain the navigational behavior of migratory birds in the wild. Our results (i) afford new insights into radical pair magnetoreception, (ii) suggest ways in which the performance of the compass could have been optimized by evolution, (iii) may provide the beginnings of an explanation for the magnetic disorientation of migratory birds exposed to anthropogenic electromagnetic noise, and (iv) suggest that radical pair magnetoreception may be more of a quantum biology phenomenon than previously realized

Migratory birds can navigate over tens of thousands of kilometers with an accuracy unobtainable for human navigators. To do so, they use their brains. In this review, we address how birds sense navigation- and orientation-relevant cues and where in their brains each individual cue is processed. When little is currently known, we make educated predictions as to which brain regions could be involved. We ask where and how multisensory navigational information is integrated and suggest that the hippocampus could interact with structures that represent maps and compass information to compute and constantly control navigational goals and directions. We also suggest that the caudolateral nidopallium could be involved in weighing conflicting pieces of information against each other, making decisions, and helping the animal respond to unexpected situations. Considering the gaps in current knowledge, some of our suggestions may be wrong. However, our main aim is to stimulate further research in this fascinating field

A new type of radiochromic film, the EBT-XD film, has been introduced with the aim to reduce the orientation effect and the lateral response artifact occurring in the use of radiochromic films together with flatbed scanners. The task of the present study is to quantify the changes of optical characteristics involved with the transition from the well-known EBT3 films to the new EBT-XD films, using the optical bench arrangement already applied by Schoenfeld et al (2014 Phys. Med. Biol. 59 3575-97). Largely reduced polarization effects and the almost complete loss of the anisotropy of the scattered light produced in a radiation-exposed film have been observed. The Rayleigh-Debye-Gans theory is used to understand these optical changes as arising from the reduced length-to-width ratio of the LiPCDA polymer crystals in the active layer of the EBT-XD film. The effect of these changes on the flatbed scanning artifacts will be shortly addressed, but treated in more detail in a further paper

Modern psychopharmacological research in humans focuses on how specific psychoactive molecules modulate oscillatory brain activity. We present state-of-the-art EEG methods applied in a resting-state drug study. Thirty healthy male nonsmokers were randomly allocated either to a nicotine group (14 subjects, 7 mg transdermal nicotine) or a placebo group (16 subjects). EEG activity was recorded in eyes-open (EO) and eyes-closed (EC) conditions before and after drug administration. A source reconstruction (minimum norm algorithm) analysis was conducted within a frequency range of 8.5-18.4 Hz subdivided into three different frequency bands. During EO, nicotine reduced the power of oscillatory activity in the 12.5- to 18.4-Hz frequency band in the left middle frontal gyrus. In contrast, in the EC condition, nicotine reduced the power in the 8.5- to 10.4-Hz frequency band in the superior frontal gyri and in the 10.5- to 12.4-Hz and 12.5- to 18.4-Hz frequency bands in the supplementary motor areas. In summary, nicotine reduced the power of the 12.5- to 18.4-Hz band in the left middle frontal gyrus during EO, and it reduced power from 8.5 to 18.4 Hz in a brain area spanning from the superior frontal gyri to the supplementary motor areas during EC. In conclusion, the results suggest that nicotine counteracts the phenomenon of anteriorization of α activity, hence potentially increasing the level of vigilance.

The cortical processing of changes in auditory input involves auditory sensory regions as well as different frontoparietal brain networks. The spatiotemporal dynamics of the activation spread across these networks has, however, not been investigated in detail so far. We here approached this issue using concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), providing us with simultaneous information on both the spatial and temporal patterns of change-related activity. We applied an auditory stimulus categorization task with switching categorization rules, allowing to analyze change-related responses as a function of the changing sound feature (pitch or duration) and the task relevance of the change. Our data show the successive progression of change-related activity from regions involved in early change detection to the ventral and dorsal attention networks, and finally the central executive network. While early change detection was found to recruit feature-specific networks involving auditory sensory but also frontal and parietal brain regions, the later spread of activity across the frontoparietal attention and executive networks was largely independent of the changing sound feature, suggesting the existence of a general feature-independent processing pathway of change-related information. Task relevance did not modulate early auditory sensory processing, but was mainly found to affect processing in frontal brain regions.

The repeated processing of a sensory stimulus, such as a picture or sound, leads to a decrement in response in neurons that fired to the initial presentation. These effects are well known from single cell recordings in the inferior temporal cortex in monkeys, and functional neuroimaging in humans on large-scale neural activity could show similar effects in extrastriate, frontal and medial temporal lobe regions. The role of specific neurotransmitters in repeated processing of information is, however, less clear. In the first part of this article, we will introduce the two concepts of repetition suppression and novelty signals, which is followed by a brief overview of pharmacological neuroimaging in humans. We will then summarize human studies suggesting that gamma-aminobutyric-acid (GABA) and acetylcholine play an important role in modulating behavioral priming and associated repetition suppression in extrastriate and frontal brain regions. Finally, we review studies on neural novelty signals in the dopaminergic mesolimbic system, and conclude that dopamine regulates the temporal aspects of novelty processing and closely relates to long-term memory encoding rather than behavioral priming. As such, this review describes differential roles of GABA, acetylcholine and dopamine in repeated stimulus processing, and further suggests that repetition suppression and neural novelty signals may not be two sides of the same coin but rather independent processes.

Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients’ changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

Even when experimental conditions are kept constant, a robust and consistent finding in both behavioral and neural experiments designed to examine multisensory processing is striking variability. Although this variability has often been considered uninteresting noise (a term that is laden with strong connotations), emerging work suggests that differences in variability may be an important aspect in describing differences in performance between individuals and groups. In the current review, derived from a symposium at the 2015 International Multisensory Research Forum in Pisa, Italy, we focus on several aspects of variability as it relates to multisensory function. This effort seeks to expand our understanding of variability at levels of coding and analysis ranging from the single neuron through large networks and on to behavioral processes, and encompasses a number of the multimodal approaches that are used to evaluate and characterize multisensory processing including single-unit neurophysiology, electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and electrocorticography (ECoG).

With the advances of cochlear implant (CI) technology, many deaf individuals can partially regain their hearing ability. However, there is a large variation in the level of recovery. Cortical changes induced by hearing deprivation and restoration with CIs have been thought to contribute to this variation. The current review aims to identify these cortical changes in postlingually deaf CI users and discusses their maladaptive or adaptive relationship to the CI outcome. Overall, intra-modal and cross-modal reorganization patterns have been identified in postlingually deaf CI users in visual and in auditory cortex. Even though cross-modal activation in auditory cortex is considered as maladaptive for speech recovery in CI users, a similar activation relates positively to lip reading skills. Furthermore, cross-modal activation of the visual cortex seems to be adaptive for speech recognition. Currently available evidence points to an involvement of further brain areas and suggests that a focus on the reversal of visual take-over of the auditory cortex may be too limited. Future investigations should consider expanded cortical as well as multi-sensory processing and capture different hierarchical processing steps. Furthermore, prospective longitudinal designs are needed to track the dynamics of cortical plasticity that takes place before and after implantation.

Target speaker identification is essential for speech enhancement algorithms in assistive devices aimed toward helping the hearing impaired. Several recent studies have reported that target speaker identification is possible through electroencephalography (EEG) recordings. If the EEG system could be reduced to acceptable size while retaining the signal quality, hearing aids could benefit from the integration with concealed EEG. To compare the performance of a multichannel around-the-ear EEG system with high-density cap EEG recordings an envelope tracking algorithm was applied in a competitive speaker paradigm. The data from 20 normal hearing listeners were concurrently collected from the traditional state-of-the-art laboratory wired EEG system and a wireless mobile EEG system with two bilaterally-placed around-the-ear electrode arrays (cEEGrids). The results show that the cEEGrid ear-EEG technology captured neural signals that allowed the identification of the attended speaker above chance-level, with 69.3% accuracy, while cap-EEG signals resulted in the accuracy of 84.8%. Further analyses investigated the influence of ear-EEG signal quality and revealed that the envelope tracking procedure was unaffected by variability in channel impedances. We conclude that the quality of concealed ear-EEG recordings as acquired with the cEEGrid array has potential to be used in the brain-computer interface steering of hearing aids.

Previous studies have observed lower visual cortex activation for visual processing in cochlear implant (CI) users compared to normal hearing controls, while others reported enhanced visual speechreading abilities in CI users. The present work investigated whether lower visual cortical activation for visual processing can be explained by a more efficient visual sensory encoding in CI users. Specifically, we investigated whether CI users show enhanced stimulus-specific adaptation for visual stimuli compared to controls. Auditory sensory adaptation was also investigated to explore the sensory specificity of the predicted effect. Twenty post-lingually deafened adult CI users and twenty age-matched controls were presented with repeated visual and auditory stimuli during simultaneous acquisition of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). By integrating EEG and fNIRS signals we found significantly enhanced visual adaptation and lower visual cortex activation in CI users compared to controls. That is, responses to repeated visual stimuli decreased more prominently in CI users than in controls. The results suggest that CI users process visual stimuli more efficiently than controls.

Background. Transcranial alternating current stimulation (tACS) is a relatively recent method suited to noninvasively modulate brain oscillations. Technically the method is similar but not identical to transcranial direct current stimulation (tDCS). While decades of research in animals and humans has revealed the main physiological mechanisms of tDCS, less is known about the physiological mechanisms of tACS. Method. Here, we review recent interdisciplinary research that has furthered our understanding of how tACS affects brain oscillations and by what means transcranial random noise stimulation (tRNS) that is a special form of tACS can modulate cortical functions. Results. Animal experiments have demonstrated in what way neurons react to invasively and transcranially applied alternating currents. Such findings are further supported by neural network simulations and knowledge from physics on entraining physical oscillators in the human brain. As a result, fine-grained models of the human skull and brain allow the prediction of the exact pattern of current flow during tDCS and tACS. Finally, recent studies on human physiology and behavior complete the picture of noninvasive modulation of brain oscillations. Conclusion. In future, the methods may be applicable in therapy of neurological and psychiatric disorders that are due to malfunctioning brain oscillations.

Transcranial alternating current stimulation (tACS) has until now mostly been administered as an alternating sinusoidal wave. Despite modern tACS stimulators being able to deliver alternating current with any arbitrary shape there has been no systematic exploration into the relative benefits of different waveforms. As tACS is a relatively new technique there is a huge parameter space of unexplored possibilities which may prove superior or complimentary to the traditional sinusoidal waveform. Here, we begin to address this with an investigation into the effects of sawtooth wave tACS on individual alpha power. Evidence from animal models suggests that the gradient and direction of an electric current should be important factors for the subsequent neural firing rate; we compared positive and negative ramp sawtooth waves to test this. An additional advantage of sawtooth waves is that the resulting artifact in the electroencephalogram (EEG) recording is significantly simpler to remove than a sine wave; accordingly we were able to observe alpha oscillations both during and after stimulation. We found that positive ramp sawtooth, but not negative ramp sawtooth, significantly enhanced alpha power during stimulation relative to sham (p < 0.01). In addition we tested for an after-effect of both sawtooth and sinusoidal stimulation on alpha power but in this case did not find any significant effect. This preliminary study paves the way for further investigations into the effect of the gradient and direction of the current in tACS which could significantly improve the usefulness of this technique.

Rhythmic brain activity plays an important role in neural processing and behavior. Features of these oscillations, including amplitude, phase, and spectrum, can be influenced by internal states (e.g., shifts in arousal, attention or cognitive ability) or external stimulation. Electromagnetic stimulation techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, and trans- cranial alternating current stimulation are used increasingly in both research and clinical settings. Currently, the mechanisms whereby time-dependent external stimuli influence population-scale oscillations remain poorly understood. Here, we provide computational insights regarding the mapping between periodic pulsatile stimulation parameters such as amplitude and frequency and the response dynamics of recurrent, nonlinear spiking neural networks. Using a cortical model built of excitatory and inhibitory neurons, we explored a wide range of stimulation intensities and frequencies systematically. Our results suggest that rhythmic stimulation can form the basis of a control paradigm in which one can manipulate the intrinsic oscillatory properties of driven networks via a plurality of input-driven mechanisms. Our results show that, in addition to resonance and entrainment, nonlinear acceleration is involved in shaping the rhythmic response of our modeled network. Such nonlinear acceleration of spontaneous and synchronous oscillatory activity in a neural network occurs in regimes of intense, high-frequency rhythmic stimulation. These results open new perspectives on the manipulation of synchro- nous neural activity for basic and clinical research.

Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed.

Recent methods that allow a noninvasive modulation of brain activity are able to modulate human cognitive behavior. Among these methods are transcranial electric stimulation and transcranial magnetic stimulation that both come in multiple variants. A property of both types of brain stimulation is that they modulate brain activity and in turn modulate cognitive behavior. Here, we describe the methods with their assumed neural mechanisms for readers from the economic and social sciences and little prior knowledge of these techniques. Our emphasis is on available protocols and experimental parameters to choose from when designing a study. We also review a selection of recent studies that have successfully applied them in the respective field. We provide short pointers to limitations that need to be considered and refer to the relevant papers where appropriate.

Vocabulary size has been suggested as a useful measure of “verbal abilities“ that correlates with speech recognition scores. Knowing more words is linked to better speech recognition. How vocabulary knowledge translates to general speech recognition mechanisms, how these mechanisms relate to offline speech recognition scores, and how they may be modulated by acoustical distortion or age, is less clear. Age-related differences in linguistic measures may predict age-related differences in speech recognition in noise performance. We hypothesized that speech recognition performance can be predicted by the efficiency of lexical access, which refers to the speed with which a given word can be searched and accessed relative to the size of the mental lexicon. We tested speech recognition in a clinical German sentence-in-noise test at two signal-to-noise ratios (SNRs), in 22 younger (18-35 yrs.) and 22 older (60-78 yrs.) listeners with normal hearing. We also assessed receptive vocabulary, lexical access time, verbal working memory, and hearing thresholds as measures of individual differences. Age group, SNR level, vocabulary size and lexical access time were significant predictors of individual speech recognition scores, but working memory and hearing threshold were not. Interestingly, longer accessing times were correlated with better speech recognition scores. Hierarchical regression models for each subset of age group and SNR showed very similar patterns: The combination of vocabulary size and lexical access time contributed most to speech recognition performance; only for the younger group at the better SNR (yielding about 85% correct speech recognition) did vocabulary size alone predict performance. Our data suggest that successful speech recognition in noise is mainly modulated by the efficiency of lexical access. This suggests that older adults’ poorer performance in the speech recognition task may have arisen from reduced efficiency in lexical access; with an average vocabulary size similar to that of younger adults, they were still slower in lexical access.

Sound localization studies have typically employed two types of tasks: absolute tasks that measured the localization of the angular location of a single sound and relative tasks that measured the localization of the angular location of a sound relative to the angular location of another sound from a different source (e.g., in the Minimum Audible Angle task). The present study investigates the localization of single sounds in the European starling (Sturnus vulgaris) with a left/right discrimination paradigm. Localization thresholds of 8–12° determined in starlings using this paradigm were much lower than the minimum audible angle thresholds determined in a previous study with the same individuals. The traditional concept of sound localization classifies the present experiment as an absolute localization task. However, we propose that the experiment presenting single sounds measured localization of the angular location of the sound relative to a non-acoustic spatial frame of reference. We discuss how the properties of the setup can determine if presentation of single sounds in a left/right discrimination paradigm comprises an absolute localization task rather than a localization task relative to a non-acoustic reference. Furthermore, the analysis methods employed may lead to quite different threshold estimates for the same data, especially in case of a response bias in left/right discrimination. We propose using an analysis method precluding effects of response bias on the threshold estimate.

Both reward based operant conditioning (OC) and reflex-based prepulse inhibition (PPI) procedures are used in sound localisation studies in mice. Since the results of both procedures are compared in the literature, it is important to assess whether they provide similar results if the same stimulus paradigm is applied. Here, we compare the sensitivity of C57BL/6 mice in OC and PPI procedures for detecting a switch in speaker location using broadband and narrowband noise stimuli and determined their minimum audible angle (MAA). In the OC procedure, we calculated d' values from the hit and false alarm rates. In the PPI procedure, we calculated the area under ROC curves from the startle response amplitudes and derived da values to obtain a sensitivity measure that corresponds to d'. For both procedures, the mean sensitivity to the speaker switch increased with an increase in angular separation. For broadband noise stimuli, a d' of up to 3.3 (OC) and a da of up to 1.1 (PPI) were observed at large speaker separations. Narrowband noise stimuli resulted in lower sensitivities in both procedures, resulting in a maximum d' of 2.0 (OC) and a maximum da of 0.3 (PPI). Using a sensitivity of 1.0 as the threshold criterion, broadband noise MAAs in the range from 32° to 46° were observed in the OC procedure whereas a broadband noise MAAs of 108° or higher were observed in the PPI procedure. In the OC procedure, narrowband noise MAAs in the range from 37° to 62° were observed. In the PPI procedure, no narrowband noise MAA could be determined since none of the subjects reached the threshold. Thus, OC procedures result in a better performance of the subjects in the sound localization task than PPI procedures, challenging the view that both procedures can be used interchangeably.

The auditory brainstem response (ABR) is a sound-evoked noninvasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, the authors discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. The authors review how interaural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized.

In adaptive feedback cancellation both the convergence speed and the computational complexity depend on the number of adaptive parameters used to model the acoustic feedback paths. To reduce the number of adaptive parameters it has been proposed to model the acoustic feedback paths as the convolution of a time-invariant common pole-zero filter and time-varying all-zero filters, enabling to track fast changes. In this paper a novel procedure to estimate the common pole-zero filter of acoustic feedback paths is presented. In contrast to previous approaches which minimize the so-called equation-error, we propose to approximate the desired output-error minimization by employing a weighted least-squares procedure motivated by the Steiglitz-McBride iteration. The estimation of the common pole-zero filter is formulated as a semidefinite programming problem, to which a constraint based on Lyapunov theory is added in order to guarantee the stability of the estimated polezero filter. Experimental results using measured acoustic feedback paths from a two-microphone behind-the-ear hearing aid show that the proposed optimization procedure using the Lyapunov constraint outperforms existing optimization procedures in terms of modelling accuracy and added stable gain.

In this contribution we focus on the problem of power spectral density (PSD) estimation from multiple microphone signals in reverberant and noisy environments. The PSD estimation method proposed in this paper is based on the maximum likelihood (ML) methodology. In particular, we derive a novel ML PSD estimation scheme that is suitable for sound scenes which besides speech and reverberation consist of an additional noise component whose second-order statistics are known. The proposed algorithm is shown to outperform an existing similar algorithm in terms of PSD estimation accuracy. Moreover, it is shown numerically that the mean squared estimation error achieved by the proposed method is near the limit set by the corresponding Cram´er-Rao lower bound. The speech dereverberation performance of a multi-channel Wiener filter (MWF) based on the proposed PSD estimators is measured using several instrumental measures and is shown to be higher than when the competing estimator is used. Moreover, we perform a speech intelligibility test where we demonstrate that both the proposed and the competing PSD estimators lead to similar intelligibility improvements.

The multichannel Wiener filter (MWF) is a well-established noise reduction technique for speech processing. Most commonly, the speech component in a selected reference microphone is estimated. The choice of this reference microphone influences the broadband output signal-to-noise ratio (SNR) as well as the speech distortion. Recently, a generalized formulation for the MWF (G-MWF) was proposed that uses a weighted sum of the individual transfer functions from the speaker to the microphones to form a better speech reference resulting in an improved broadband output SNR. For the MWF, the influence of the phase reference is often neglected, because it has no impact on the narrow-band output SNR. The G-MWF allows an arbitrary choice of the phase reference especially in the context of spatially distributed microphones. In this work, we demonstrate that the phase reference determines the overall transfer function and hence has an impact on both the speech distortion and the broadband output SNR. We propose two speech references that achieve a better signal-to-reverberation ratio (SRR) and an improvement in the broadband output SNR. Both proposed references are based on the phase of a delay-and-sum beamformer. Hence, the time-difference-of-arrival (TDOA) of the speech source is required to align the signals. The different techniques are compared in terms of SRR and SNR performance.

Conventional statistical clean speech estimators, like the Wiener filter, are frequently used for the spectro-temporal enhancement of noise corrupted speech. Most of these approaches estimate the clean speech independently for each time-frequency point, neglecting the structure of the underlying speech sound. In this work, we derive a statistical estimator that explicitly takes into account information about the characteristic structure of voiced speech by means of a harmonic signal model. To this end, we also present a way to estimate a harmonic model-based clean speech representation and the corresponding error variance directly in the short-time Fourier transform domain. The resulting estimator is optimal in the minimum-mean-squared error sense and can conveniently be formulated in terms of a multichannel Wiener filter. The proposed estimator outperforms several reference algorithms in terms of speech quality and intelligibility as predicted by instrumental measures.

Objective: To use a computer model of impaired hearing to explore the effects of a physiologically-inspired hearing-aid algorithm on a range of psychoacoustic measures. Design: A computer model of a hypothetical impaired listener’s hearing was constructed by adjusting parameters of a computer model of normal hearing. Absolute thresholds, estimates of compression, and frequency selectivity (summarized to a hearing profile) were assessed using this model with and without pre-processing the stimuli by a hearing-aid algorithm. The influence of different settings of the algorithm on the impaired profile was investigated. To validate the model predictions, the effect of the algorithm on hearing profiles of human impaired listeners was measured. Study sample: A computer model simulating impaired hearing (total absence of basilar membrane compression) was used, and three hearing-impaired listeners participated. Results: The hearing profiles of the model and the listeners showed substantial changes when the test stimuli were pre-processed by the hearing-aid algorithm. These changes consisted of lower absolute thresholds, steeper temporal masking curves, and sharper psychophysical tuning curves. Conclusion: The hearing-aid algorithm affected the impaired hearing profile of the model to approximate a normal hearing profile. Qualitatively similar results were found with the impaired listeners’ hearing profiles.

This paper describes a technique for isolating the brain activity associated with melodic pitch processing. The magnetoencephalograhic (MEG) response to a four note, diatonic melody built of French horn notes, is contrasted with the response to a control sequence containing four identical, “tonic” notes. The transient response (TR) to the first note of each bar is dominated by energy-onset activity; the melody processing is observed by contrasting the TRs to the remaining melodic and tonic notes of the bar (2–4). They have uniform shape within a tonic or melodic sequence which makes it possible to fit a 4-dipole model and show that there are two sources in each hemisphere—a melody source in the anterior part of Heschl’s gyrus (HG) and an onset source about 10 mm posterior to it, in planum temporale (PT). The N1m to the initial note has a short latency and the same magnitude for the tonic and the melodic sequences. The melody activity is distinguished by the relative sizes of the N1m and P2m components of the TRs to notes 2–4. In the anterior source a given note elicits a much larger N1m-P2m complex with a shorter latency when it is part of a melodic sequence. This study shows how to isolate the N1m, energy-onset response in PT, and produce a clean melody response in the anterior part of auditory cortex (HG).

We report a systematic exploration of the interrelation of sound intensity, ear of entry, individual loudness judgments, and brain activity across hemispheres, using auditory functional magnetic resonance imaging (fMRI). The stimuli employed were 4 kHz-bandpass filtered noise stimuli, presented monaurally to each ear at levels from 37 to 97 dB SPL. One diotic condition and a silence condition were included as control conditions. Normal hearing listeners completed a categorical loudness scaling procedure with similar stimuli before auditory fMRI was performed. The relationship between brain activity, as inferred from blood oxygenation level dependent (BOLD) contrasts, and both sound intensity and loudness estimates were analyzed by means of linear mixed effects models for various anatomically defined regions of interest in the ascending auditory pathway and in the cortex. The results indicate distinct functional differences between midbrain and cortical areas as well as between specific regions within auditory cortex, suggesting a systematic hierarchy in terms of lateralization and the representation of sensory stimulation and perception.

Loudness is the perceptual correlate of the physical intensity of a sound. However, loudness judgments depend on a variety of other variables and can vary considerably between individual listeners. While functional magnetic resonance imaging (fMRI) has been extensively used to characterize the neural representation of physical sound intensity in the human auditory system, only few studies have also investigated brain activity in relation to individual loudness. The physiological correlate of loudness perception is not yet fully understood. The present study systematically explored the interrelation of sound pressure level, ear of entry, individual loudness judgments, and fMRI activation along different stages of the central auditory system and across hemispheres for a group of normal hearing listeners. 4-kHz-bandpass filtered noise stimuli were presented monaurally to each ear at levels from 37 to 97 dB SPL. One diotic condition and a silence condition were included as control conditions. The participants completed a categorical loudness scaling procedure with similar stimuli before auditory fMRI was performed. The relationship between brain activity, as inferred from blood oxygenation level dependent (BOLD) contrasts, and both sound level and loudness estimates were analyzed by means of functional activation maps and linear mixed effects models for various anatomically defined regions of interest in the ascending auditory pathway and in the cortex. Our findings are overall in line with the notion that fMRI activation in several regions within auditory cortex as well as in certain stages of the ascending auditory pathway might be more a direct linear reflection of perceived loudness rather than of sound pressure level. The results indicate distinct functional differences between midbrain and cortical areas as well as between specific regions within auditory cortex, suggesting a systematic hierarchy in terms of lateralization and the representation of level and loudness.

A temporally acute binaural system can help to resolve inherent fluctuations in binaural information that are often present in complex auditory scenes. Using a broadband noise stimulus that rapidly alternates between two different values of interaural time difference(ITD), the ability of the binaural system to hear the lateral position resulting from one of the ITD values was investigated. Results show that listeners are able to accurately lateralize brief noise tokens of only 3–7 ms in duration. In two subsequent experiments, the role of an amplitude modulation (AM) imposed on the ITD-switching stimulus used in the first experiment was tested. For wideband stimuli, the temporal position of the ITD target relative to the phase of the AM did not influence absolute lateralization or detection performance. When the stimuli were narrowband, however, detection of the ITD target was best when temporally positioned in the rising portion of the AM. These experiments illustrate that the auditory system is capable of making accurate lateral estimates of very brief moments of ITD information. Furthermore, for these instantaneous changes in ITD information, the stimulus bandwidth can influence the role of envelope cues for the readout of binaural information.

Speech intelligibility in multitalker settings improves when the target speaker is spatially separated from the interfering speakers. A factor that may contribute to this improvement is the improved detectability of target-speech components due to binaural interaction in analogy to the Binaural Masking Level Difference (BMLD). This would allow listeners to hear target speech components within specific time-frequency intervals that have a negative SNR, similar to the improvement in the detectability of a tone in noise when these contain disparate interaural difference cues. To investigate whether these negative-SNR target-speech components indeed contribute to speech intelligibility, a stimulus manipulation was performed where all target components were removed when local SNRs were smaller than a certain criterion value. It can be expected that for sufficiently high criterion values target speech components will be removed that do contribute to speech intelligibility. For spatially separated speakers, assuming that a BMLD-like detection advantage contributes to intelligibility, degradation in intelligibility is expected already at criterion values below 0 dB SNR. However, for collocated speakers it is expected that higher criterion values can be applied without impairing speech intelligibility. Results show that degradation of intelligibility for separated speakers is only seen for criterion values of 0 dB and above, indicating a negligible contribution of a BMLD-like detection advantage in multitalker settings. These results show that the spatial benefit is related to a spatial separation of speech components at positive local SNRs rather than to a BMLD-like detection improvement for speech components at negative local SNRs.

Abstract | The Oldenburg Sentence Test for Children (OLKISA) has been used for speech audiometry with children for several years. In principle, the test procedure is also applicable for adults. The necessary evaluation and corresponding values for comparison are described here. The results of measurements with 40 normal hearing adults show that the OLKISA can be conducted with adults in quiet as well as in noise. For the group of test subjects under examination and after eliminating the training effect, a range of speech reception thresholds for 50 % intelligibility of 18.8 ± 2.2 dB SPL was found in quiet and a range of -7.2 ± 1.2 dB SNR was found in noise (Oldenburg noise) for adaptive measurements. The slope of the psychometric function of the OLKISA for the examined population of test subjects was 12.8 ± 0.8 %/dB in quiet and 13.7 ± 1.3 %/dB in noise. ### Zusammenfassung | Der Oldenburger Kinder-Satztest (OLKISA) wird seit Jahren in der Sprachaudiometrie mit Kindern eingesetzt. Grundsätzlich ist das Verfahren auch mit Erwachsenen durchführbar. Die dafür notwendige Evaluation und entsprechende Vergleichswerte werden hier vorgestellt. Die Ergebnisse der Messungen mit 40 normalhörenden erwachsenen Probanden zeigen, dass der OLKISA sowohl in Ruhe als auch im Störgeräusch mit Erwachsenen verwendet werden kann. Bei adaptiv durchgeführten Messungen der Sprachverständlichkeitsschwelle für 50 % Verständlichkeit ergaben sich mit der untersuchten Probandengruppe nach Ausschluss des Trainingseffekts Bereiche von 18,8 ± 2,2 dB SPL in Ruhe und -7,2 ± 1,2 dB SNR im Störgeräusch (Oldenburger Rauschen). Die Steigung der psychometrischen Funktion des OLKISA für die untersuchte Probandengruppe lag bei 12,8 ± 0,8 %/dB in Ruhe und 13,7 ± 1,3 %/dB im Störgeräusch.

Brief deviations of interaural correlation (IAC) can provide valuable cues for detection, segregation and localization of acoustic signals. This study investigated the processing of such “binaural gaps” in continuously running noise (100-2000 Hz), in comparison to silent “monaural gaps”, by measuring late auditory evoked potentials (LAEPs) and perceptual thresholds with novel, iteratively optimized stimuli. Mean perceptual binaural gap duration thresholds exhibited a major asymmetry: they were substantially shorter for uncorrelated gaps in correlated and anticorrelated reference noise (1.75 ms and 4.1 ms) than for correlated and anticorrelated gaps in uncorrelated reference noise (26.5 ms and 39.0 ms). The thresholds also showed a minor asymmetry: they were shorter in the positive than in the negative IAC range. The mean behavioral threshold for monaural gaps was 5.5 ms. For all five gap types, the amplitude of LAEP components N1 and P2 increased linearly with the logarithm of gap duration. While perceptual and electrophysiological thresholds matched for monaural gaps, LAEP thresholds were about twice as long as perceptual thresholds for uncorrelated gaps, but half as long for correlated and anticorrelated gaps. Nevertheless, LAEP thresholds showed the same asymmetries as perceptual thresholds. For gap durations below 30 ms, LAEPs were dominated by the processing of the leading edge of a gap. For longer gap durations, in contrast, both the leading and the lagging edge of a gap contributed to the evoked response. Formulae for the equivalent rectangular duration (ERD) of the binaural system’s temporal window were derived for three common window shapes. The psychophysical ERD was 68 ms for diotic and about 40 ms for anti- and uncorrelated noise. After a nonlinear Z-transform of the stimulus IAC prior to temporal integration, ERDs were about 10 ms for reference correlations of ±1 and 80 ms for uncorrelated reference. Hence, a physiologically motivated peripheral nonlinearity changed the rank order of ERDs across experimental conditions in a plausible manner.

Vowel identification in noise using consonant-vowel-consonant (CVC) logatomes was used to investigate a possible interplay of speech information from different frequency regions. It was hypothesized that the periodicity conveyed by the temporal envelope of a high frequency stimulus can enhance the use of the information carried by auditory channels in the low-frequency region that share the same periodicity. It was further hypothesized that this acts as a strobe-like mechanism and would increase the signal-to-noise ratio for the voiced parts of the CVCs. In a first experiment, different high-frequency cues were provided to test this hypothesis, whereas a second experiment examined more closely the role of amplitude modulations and intact phase information within the high-frequency region (4-8 kHz). CVCs were either natural or vocoded speech (both limited to a low-pass cutoff-frequency of 2.5 kHz) and were presented in stationary 3-kHz low-pass filtered masking noise. The experimental results did not support the hypothesized use of periodicity information for aiding low-frequency perception.

Sensorineural hearing loss typically results in a steepened loudness function and a reduced dynamic range from elevated thresholds to uncomfortably loud levels for narrowband and broadband signals. Restoring narrowband loudness perception for hearing-impaired (HI) listeners can lead to overly loud perception of broadband signals and it is unclear how binaural presentation affects loudness perception in this case. Here, loudness perception quantified by categorical loudness scaling for nine normal-hearing (NH) and ten HI listeners was compared for signals with different bandwidth and different spectral shape in monaural and in binaural conditions. For the HI listeners, frequency- and level-dependent amplification was used to match the narrowband monaural loudness functions of the NH listeners. The loudness functions for NH and HI listeners showed good agreement for monaural broadband signals. However, HI listeners showed substantially greater loudness for binaural broadband signals than for the NH listeners: on average a 14.1 dB lower level was required to reach “very loud” (range 30.8 to -3.7 dB). Overall, with narrowband loudness compensation, a given binaural loudness for broadband signals above “medium loud” was reached at systematically lower levels for HI than for NH listeners. Such increased binaural loudness summation was not found for loudness categories below “medium loud” or for narrowband signals. Large individual variations in the increased loudness summation were observed and could not be explained by the audiogram or the narrowband loudness functions.

A framework for simulating auditory discrimination experiments, based on an approach from Schädler, Warzybok, Hochmuth, and Kollmeier [(2015). Int. J. Audiol. 54, 100–107] which was originally designed to predict speech recognition thresholds, is extended to also predict psychoacoustic thresholds. The proposed framework is used to assess the suitability of different auditory-inspired feature sets for a range of auditory discrimination experiments that included psychoacoustic as well as speech recognitionexperiments in noise. The considered experiments were 2 kHz tone-in-broadband-noise simultaneous masking depending on the tone length, spectral masking with simultaneously presented tone signals and narrow-band noise maskers, and German Matrix sentence test reception threshold in stationary and modulated noise. The employed feature sets included spectro-temporal Gabor filter bank features, Mel-frequency cepstral coefficients, logarithmically scaled Mel-spectrograms, and the internal representation of the Perception Model from Dau, Kollmeier, and Kohlrausch [(1997). J. Acoust. Soc. Am. 102(5), 2892–2905]. The proposed framework was successfully employed to simulate all experiments with a common parameter set and obtain objective thresholds with less assumptions compared to traditional modeling approaches. Depending on the feature set, the simulated reference-free thresholds were found to agree with—and hence to predict—empirical data from the literature. Across-frequency processing was found to be crucial to accurately model the lower speech reception threshold in modulated noise conditions than in stationary noise conditions.

Speech intelligibility is strongly affected by the presence of maskers. Depending on the spectro-temporal structure of the masker and its similarity to the target speech, different masking aspects can occur which are typically referred to as energetic, amplitude modulation, and informational masking. In this study speech intelligibility and speech detection was measured in maskers that vary systematically in the time-frequency domain from steady-state noise to a single interfering talker. Male and female target speech was used in combination with maskers based on speech for the same or different gender. Observed data were compared to predictions of the speech intelligibility index, extended speech intelligibility index, multi-resolution speech-based envelope-power-spectrum model, and the short-time objective intelligibility measure. The different models served as analysis tool to help distinguish between the different masking aspects. Comparison shows that overall masking can to a large extent be explained by short-term energetic masking. However, the other masking aspects (amplitude modulation an informational masking) influence speech intelligibility as well. Additionally, it was obvious that all models showed considerable deviations from the data. Therefore, the current study provides a benchmark for further evaluation of speech prediction models.

Background: Field tests and guided walks in real environments show that the benefit from hearing aid (HA) signal processing in real-life situations is typically lower than the predicted benefit found in laboratory studies. This suggests that laboratory test outcome measures are poor predictors of real-life HA benefits. However, a systematic evaluation of algorithms in the field is difficult due to the lack of reproducibility and control of the test conditions. Virtual acoustic environments that simulate real-life situations may allow for a systematic and reproducible evaluation of HAs under more realistic conditions, thus providing a better estimate of real-life benefit than established laboratory tests. Purpose: To quantify the difference in HA performance between a laboratory condition and more realistic conditions based on technical performance measures using virtual acoustic environments, and to identify the factors affecting HA performance across the tested environments. Research Design: A set of typical HA beamformer algorithms was evaluated in virtual acoustic environments of different complexity. Performance was assessed based on established technical performance measures, including perceptual model predictions of speech quality and speech intelligibility. Virtual acoustic environments ranged from a simple static reference condition to more realistic complex scenes with dynamically moving sound objects. Results: HA benefit, as predicted by signal-to-noise ratio (SNR) and speech intelligibility measures, differs between the reference condition and more realistic conditions for the tested beamformer algorithms. Other performance measures, such as speech quality or binaural degree of diffusiveness, do not show pronounced differences. However, a decreased speech quality was found in specific conditions. A correlation analysis showed a significant correlation between room acoustic parameters of the sound field and HA performance. The SNR improvement in the reference condition was found to be a poor predictor of HA performance in terms of speech intelligibility improvement in the more realistic conditions. Conclusions: Using several virtual acoustic environments of different complexity, a systematic difference in HA performance between a simple reference condition and more realistic environments was found, which may be related to the discrepancy between laboratory and real-life HA performance reported previously.

The purpose of this study was to develop, optimize, and evaluate the Russian digit triplet test for hearing screening in noise. The speech material consists of sequences of three digits like 3-2-8. A closed-set test format enables its automated administration. The speech material was optimized and evaluated for headphone and landline telephone presentation. Results were compared to digit triplet tests in other languages. First, the speech material was recorded and optimized with respect to intelligibility by applying level corrections on the basis of digit-specific speech reception thresholds (SRT) defined as signal-to-noise ratio yielding 50% intelligibility. In the following, evaluation measurements were conducted to verify test list equivalency and to obtain reference data for listeners with normal hearing. Evaluation measurements showed small differences across the six test lists. Mean slopes of the list-specific recognition functions were 14.8 %/dB and 14.4 %/dB for the headphone and the landline telephone version, respectively. The reference SRT with corresponding standard deviation for the headphone and the landline telephone version were – 11.7 ± 0.9 dB and – 8.5 ± 0.6 dB, respectively. The difference of 3.2 dB in SRT between the two test versions could be explained by the limited frequency bandwidth for the transmission over landline telephone. Both versions were shown to be reliable tests for screening speech recognition in noise and to be comparable with other languages.

To characterize the individual patient’s hearing impairment as obtained with the matrix sentence recognition test, a simulation Framework for Auditory Discrimination Experiments (FADE) is extended here using the Attenuation and Distortion (A+D) approach by Plomp as a blueprint for setting the individual processing parameters. FADE has been shown to predict the outcome of both speech recognition tests and psychoacoustic experiments based on simulations using an automatic speech recognition system requiring only few assumptions. It builds on the closed-set matrix sentence recognition test which is advantageous for testing individual speech recognition in a way comparable across languages. Individual predictions of speech recognition thresholds in stationary and in fluctuating noise were derived using the audiogram and an estimate of the internal level uncertainty for modeling the individual Plomp curves fitted to the data with the Attenuation (A-) and Distortion (D-) parameters of the Plomp approach. The “typical” audiogram shapes from Bisgaard et al with or without a “typical” level uncertainty and the individual data were used for individual predictions. As a result, the individualization of the level uncertainty was found to be more important than the exact shape of the individual audiogram to accurately model the outcome of the German Matrix test in stationary or fluctuating noise for listeners with hearing impairment. The prediction accuracy of the individualized approach also outperforms the (modified) Speech Intelligibility Index approach which is based on the individual threshold data only.

The auditory brainstem response (ABR) is an evoked potential that reflects the responses to sound by brainstem neural centers. The binaural interaction component (BIC) is obtained by subtracting the sum of the monaural ABR responses from the binaural response. Its latency and amplitude change in response to variations in binaural cues. The BIC is thus thought to reflect the activity of binaural nuclei and is used to non-invasively test binaural processing. However, any conclusions are limited by a lack of knowledge of the relevant processes at the level of individual neurons. The aim of this study was to characterize the ABR and BIC in the barn owl, an animal where the ITD-processing neural circuits are known in great detail. We recorded ABR responses to chirps and to 1 and 4 kHz tones from anesthetized barn owls. General characteristics of the barn owl ABR were similar to those observed in other bird species. The most prominent peak of the BIC was associated with nucleus laminaris and is thus likely to reflect the known processes of ITD computation in this nucleus. However, the properties of the BIC were very similar to previously published mammalian data and did not reveal any specific diagnostic features. For example, the polarity of the BIC was negative, which indicates a smaller response to binaural stimulation than predicted by the sum of monaural responses. This is contrary to previous predictions for an excitatory-excitatory system such as nucleus laminaris. Similarly, the change in BIC latency with varying ITD was not distinguishable from mammalian data. Contrary to previous predictions, this behavior appears unrelated to the known underlying neural delay-line circuitry. In conclusion, the generation of the BIC is currently inadequately understood and common assumptions about the BIC need to be reconsidered when interpreting such measurements.

Sensory coding has long been discussed in terms of a dichotomy between spike timing and rate coding. However, recent studies found that in primate mechanoperception and other sensory systems, spike rates and timing of cell populations complement each other. They simultaneously carry information about different stimulus properties in a multiplexed way. Here, we present evidence for multiplexed encoding of tactile skin stimulation in the tiny population of leech mechanoreceptors, consisting of only 10 cells of two types with overlapping receptive fields. Each mechanoreceptor neuron of the leech varies spike count and response latency to both touch intensity and location, leading to ambiguous responses to different stimuli. Nevertheless, three different stimulus estimation techniques consistently reveal that the neuronal population allows reliable decoding of both stimulus properties. For the two mechanoreceptor types, the transient responses of T (touch) cells and the sustained responses of P (pressure) cells, the relative timing of the first spikes of two mechanoreceptors encodes stimulus location, whereas summed spike counts represent touch intensity. Differences between the cell types become evident in responses to combined stimulus properties. The best estimation performance for stimulus location is obtained from the relative first spike timing of the faster and temporally more precise T cells. Simultaneously, the sustained responses of P cells indicate touch intensity by summed spike counts and stimulus duration by the duration of spike responses. The striking similarities of these results with previous findings on primate mechanosensory afferents suggest multiplexed population coding as a general principle of somatosensation. SIGNIFICANCE STATEMENT Multiplexing, the simultaneous encoding of different stimulus properties by distinct neuronal response features, has recently been suggested as a mechanism used in several sensory systems, including primate somatosensation. While a rigorous experimental verification of the multiplexing hypothesis is difficult to accomplish in a complex vertebrate system, it is feasible for a small population of individually characterized leech neurons. Monitoring the responses of all four mechanoreceptors innervating a patch of skin revealed striking similarities between touch encoding in the primate and the leech: summed spike counts represent stimulus intensity, whereas relative timing of first spikes encodes stimulus location. These findings suggest that multiplexed population coding is a general mechanism of touch encoding common to species as different as man and worm.

Many sensory neurons encode temporal information by detecting coincident arrivals of synaptic inputs. In the mammalian auditory brainstem, binaural neurons of the medial superior olive (MSO) are known to act as coincidence detectors, whereas in the lateral superior olive (LSO) roles of coincidence detection have remained unclear. LSO neurons receive excitatory and inhibitory inputs driven by ipsilateral and contralateral acoustic stimuli, respectively, and vary their output spike rates according to interaural level differences. In addition, LSO neurons are also sensitive to binaural phase differences of low-frequency tones and envelopes of amplitude-modulated (AM) sounds. Previous physiological recordings in vivo found considerable variations in monaural AM-tuning across neurons. To investigate the underlying mechanisms of the observed temporal tuning properties of LSO and their sources of variability, we used a simple coincidence counting model and examined how specific parameters of coincidence detection affect monaural and binaural AM coding. Spike rates and phase-locking of evoked excitatory and spontaneous inhibitory inputs had only minor effects on LSO output to monaural AM inputs. In contrast, the coincidence threshold of the model neuron affected both the overall spike rates and the half-peak positions of the AM-tuning curve, whereas the width of the coincidence window merely influenced the output spike rates. The duration of the refractory period affected only the low-frequency portion of the monaural AM-tuning curve. Unlike monaural AM coding, temporal factors, such as the coincidence window and the effective duration of inhibition, played a major role in determining the trough positions of simulated binaural phase-response curves. In addition, empirically-observed level-dependence of binaural phase-coding was reproduced in the framework of our minimalistic coincidence counting model. These modeling results suggest that coincidence detection of excitatory and inhibitory synaptic inputs is essential for LSO neurons to encode both monaural and binaural AM sounds.

Evidence from animal and human studies suggests that moderate acoustic exposure, causing only transient threshold elevation, can nonetheless cause “hidden hearing loss” that interferes with coding of suprathreshold sound. Such noise exposure destroys synaptic connections between cochlear hair cells and auditory nerve fibers; however, there is no clinical test of this synaptopathy in humans. In animals, synaptopathy reduces the amplitude of auditory brainstem response (ABR) wave-I. Unfortunately, ABR wave-I is difficult to measure in humans, limiting its clinical use. Here, using analogous measurements in humans and mice, we show that the effect of masking noise on the latency of the more robust ABR wave-V mirrors changes in ABR wave-I amplitude. Furthermore, in our human cohort, the effect of noise on wave-V latency predicts perceptual temporal sensitivity. Our results suggest that measures of the effects of noise on ABR wave-V latency can be used to diagnose cochlear synaptopathy in humans. SIGNIFICANCE STATEMENT Although there are suspicions that cochlear synaptopathy affects humans with normal hearing thresholds, no one has yet reported a clinical measure that is a reliable marker of such loss. By combining human and animal data, we demonstrate that the latency of auditory brainstem response wave-V in noise reflects auditory nerve loss. This is the first study of human listeners with normal hearing thresholds that links individual differences observed in behavior and auditory brainstem response timing to cochlear synaptopathy. These results can guide development of a clinical test to reveal this previously unknown form of noise-induced hearing loss in humans

Histone methylation is an important epigenetic mark leading to changes in DNA accessibility and transcription. Here, we investigate immunoreactivity against the euchromatic histone-lysine N-methyltransferase EHMT2 and its catalyzed mono- and dimethylation marks at histone 3 lysine 9 (H3K9me1 and H3K9me2) during postnatal differentiation of the mouse central auditory system. In the brainstem, expression of EHMT2 was high in the first postnatal week and down-regulated thereafter. In contrast, immunoreactivity in the auditory cortex (AC) remained high during the first year of life. This difference might be related to distinct demands for adult plasticity. Analyses of two deaf mouse models, namely Cldn14 −/− and Cacna1d −/−, demonstrated that sound-driven or spontaneous activity had no influence on EHMT2 immunoreactivity. The methylation marks H3K9me1 and H3K9me2 were high throughout the auditory system up to 1 year. Young auditory neurons showed immunoreactivity against both methylations at similar intensities, whereas many mature neurons showed stronger labeling for either H3K9me1 or H3K9me2. These differences were only poorly correlated with cell types. To identify methyltransferases contributing to the persistent H3K9me1 and H3K9me2 marks in the adult brainstem, EHMT1 and the retinoblastoma-interacting zinc-finger protein RIZ1 were analyzed. Both were down-regulated during brainstem development, similar to EHMT2. Contrary to EHMT2, EHMT1 was also down-regulated in adult cortical areas. Together, our data reveal a marked difference in EHMT2 levels between mature brainstem and cortical areas and a decoupling between EHMT2 abundance and histone 3 lysine 9 methylations during brainstem differentiation. Furthermore, EHMT1 and EHMT2 are differentially expressed in cortical areas.

γ-crystallins are major components of the vertebrate lens but show expression in other tissues as well. Their extralenticular functions remain so far unclear. Here, we explored such roles in the rodent superior olivary complex in which previous analysis demonstrated developmentally regulated expression of Crygd, Cryge and Crygn. Immunohistochemistry with novel antibodies against Crygd/e and Crygn indicate that expression of Crygd/e was moderate and varied between the perinatal superior olivary complex of mice, rats, and gerbils. Crygn-immunoreactivity was more robust and consistently highest in the medial nucleus of the trapezoid body, but also present in other nuclei of the superior olivary complex. To analyze the function of Crygn in the auditory hindbrain, we used a Crygn allele with a floxed exon 2. Upon pairing with Egr2::Cre mice, exon 2, encoding the first two greek key motifs of Crygn, was deleted in the developing auditory hindbrain. Anatomical analysis of these mice revealed a 20% volume reduction in the medial nucleus of the trapezoid body and a 7% reduction in the lateral superior olive at postnatal day 25. This was due to cell loss between postnatal days 4 and 25, whereas cell size was unaffected. Auditory brainstem responses showed normal threshold but a significant increase in the amplitude of wave IV. Crygn is hence required for postmigratory survival and proper function of auditory hindbrain neurons. These results ascertain for the first time an essential extralenticular role for γ-crystallins in vivo.

Oscillatory EEG activity in the human brain with frequencies in the gamma range (approx. 30-80Hz) is known to be relevant for a large number of cognitive processes. Interestingly, each subject reveals an individual frequency of the auditory gamma-band response (GBR) that coincides with the peak in the auditory steady state response (ASSR). A common resonance frequency of auditory cortex seems to underlie both the individual frequency of the GBR and the peak of the ASSR. This review sheds light on the functional role of oscillatory gamma activity for auditory processing. For successful processing, the auditory system has to track changes in auditory input over time and store information about past events in memory which allows the construction of auditory objects. Recent findings support the idea of gamma oscillations being involved in the partitioning of auditory input into discrete samples to facilitate higher order processing. We review experiments that seem to suggest that inter-individual differences in the resonance frequency are behaviorally relevant for gap detection and speech processing. A possible application of these resonance frequencies for brain computer interfaces is illustrated with regard to optimized individual presentation rates for auditory input to correspond with endogenous oscillatory activity. This article is part of a Special Issue entitled SI: Auditory working memory

The functional relevance of brain oscillations in the alpha frequency range (8-13 Hz) has been repeatedly investigated through the use of rhythmic visual stimulation. The underlying mechanism of the steady-state visual evoked potential (SSVEP) measured in EEG during rhythmic stimulation, however, is not known. There are two hypotheses on the origin of SSVEPs: entrainment of brain oscillations and superposition of event-related responses (ERPs). The entrainment but not the superposition hypothesis justifies rhythmic visual stimulation as a means to manipulate brain oscillations, because superposition assumes a linear summation of single responses, independent from ongoing brain oscillations. Here, we stimulated participants with a rhythmic flickering light of different frequencies and intensities. We measured entrainment by comparing the phase coupling of brain oscillations stimulated by rhythmic visual flicker with the oscillations induced by arrhythmic jittered stimulation, varying the time, stimulation frequency, and intensity conditions. In line with a theoretical concept of entrainment (the so called Arnold tongue), we found the phase coupling to be more pronounced with increasing stimulation intensity as well as at stimulation frequencies closer to each participant's intrinsic frequency. Only inside the Arnold tongue did the conditions significantly differ from the jittered stimulation. Furthermore, even in a single sequence of an SSVEP, we found non-linear features (intermittency of phase locking) that contradict the linear summation of single responses, as assumed by the superposition hypothesis. Our findings provide unequivocal evidence that visual rhythmic stimulation entrains brain oscillations, thus validating the approach of rhythmic stimulation as a manipulation of brain oscillations

Many studies have proven transcranial alternating current stimulation (tACS) to manipulate brain activity. Until now it is not known, however, how these manipulations in brain activity are represented in brain metabolism or how spatially specific these changes are. Alpha-tACS has been shown to enhance the amplitude of the individual alpha frequency (IAF) and a negative correlation between alpha amplitude and occipital BOLD signal was reported in numerous EEG/fMRI experiments. Thus, alpha-tACS was chosen to test the effects of tACS on the BOLD signal. A reduction thereof was expected during alpha-tACS which shows the spatial extent of tACS effects beyond modeling studies. Three groups of subjects were measured in an MRI scanner, receiving tACS at either their IAF (N=11), 1Hz (control; N=12) or sham (i.e., no stimulation - a second control; N=11) while responding to a visual vigilance task. Stimulation was administered in an interleaved pattern of tACS-on runs and tACS-free baseline periods. The BOLD signal was analyzed in response to tACS-onset during resting state and in response to seldom target stimuli. Alpha-tACS at 1.0mA reduced the task-related BOLD response to visual targets in the occipital cortex as compared to tACS-free baseline periods. The deactivation was strongest in an area where the BOLD signal was shown to correlate negatively with alpha amplitude. A direct effect of tACS on resting state BOLD signal levels could not be shown. Our findings suggest that tACS-related changes in BOLD activity occur only as a modulation of an existing BOLD response

Cross-frequency coupling (CFC) has been suggested to constitute a highly flexible mechanism for cortical information gating and processing, giving rise to conscious perception and various higher cognitive functions in humans. In particular, it might provide an elegant tool for information integration across several spatiotemporal scales within nested or coupled neuronal networks. However, it is currently unknown whether low-frequency (theta/alpha) or high-frequency gamma oscillations orchestrate cross-frequency interactions, raising the question of who is master and who is slave. While correlative evidence suggested that at least two distinct CFC modes exist, namely, phase-amplitude-coupling (PAC) and amplitude-envelope correlations (AEC), it is currently unknown whether they subserve distinct cortical functions. Novel non-invasive brain stimulation tools, such as transcranial alternating current stimulation (tACS), now provide the unique opportunity to selectively entrain the low- or high-frequency component and study subsequent effects on CFC. Here, we demonstrate the differential modulation of CFC during selective entrainment of alpha or gamma oscillations. Our results reveal that entrainment of the low-frequency component increased PAC, where gamma power became preferentially locked to the trough of the alpha oscillation, while gamma-band entrainment enhanced AECs and reduced alpha power. These results provide causal evidence for the functional role of coupled alpha and gamma oscillations for visual processing

Cryptochromes are ubiquitously expressed in various animal tissues including the retina. Some cryptochromes are involved in regulating circadian activity. Cryptochrome proteins have also been suggested to mediate the primary mechanism in light-dependent magnetic compass orientation in birds. Cryptochrome 1b (Cry1b) exhibits a unique carboxy terminus exclusively found in birds so far, which might be indicative for a specialised function. Cryptochrome 1a (Cry1a) is so far the only cryptochrome protein that has been localised to specific cell types within the retina of migratory birds. Here we show that Cry1b, an alternative splice variant of Cry1a, is also expressed in the retina of migratory birds, but it is primarily located in other cell types than Cry1a. This could suggest different functions for the two splice products. Using diagnostic bird-specific antibodies (that allow for a precise discrimination between both proteins), we show that Cry1b protein is found in the retinae of migratory European robins (Erithacus rubecula), migratory Northern Wheatears (Oenanthe oenanthe) and pigeons (Columba livia). In all three species, retinal Cry1b is localised in cell types which have been discussed as potentially well suited locations for magnetoreception: Cry1b is observed in the cytosol of ganglion cells, displaced ganglion cells, and in photoreceptor inner segments. The cytosolic rather than nucleic location of Cry1b in the retina reported here speaks against a circadian clock regulatory function of Cry1b and it allows for the possible involvement of Cry1b in a radical-pair-based magnetoreception mechanism.

Inspired by physiological studies on the human auditory system and by results from psychoacoustics, an amplitude modulation filter bank (AMFB) has been developed and successfully applied to feature extraction for automatic speech recognition (ASR) in earlier work. Here, we address the question as to which amplitude modulation (AM) frequency decomposition leads to optimal ASR performance by proposing a parameterized functional relationship between modulation center frequency and modulation bandwidth. Word error rates (WERs) of ASR experiments with 1551 different AMFBs are systematically evaluated and compared, resulting in the identification of a comparatively narrow range of optimal modulation frequency to modulation bandwidth characteristics. To integrate modulation processing with deep neural network (DNN) acoustic modeling, we propose merging of modulation filter coefficients with DNN weights prior to a final training step and an improved mean-variance normalization scheme for AMFBs. These modifications are shown to result in further reduction of WERs and are indicative of the proposed system's improved generalization ability, when compared across corpora of 100-960 h of data with mismatched training and test conditions. Analysis of DNN-learned temporal AM filtering properties is carried out and implications for the relevance of different modulation regions as well as the relation to psychoacoustic findings are discussed. ASR experiments with the proposed system demonstrate a high degree of robustness against extrinsic acoustic distortions, resulting in, e.g., an average WER of 9.79\% on the Aurora-4 task.

Objective Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Methods Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. Results 269 patients with PD-MCI (age 67.8 +/- 7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2 +/- 11.6) were included. PD-MCI subtypes were 39.4\% non-amnestic single domain, 30.5\% amnestic multiple domain, 23.4\% non-amnestic multiple domain and 6.7\% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. Conclusions This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Introduction: Cognitive impairment is a common and disabling non-motor symptom in Parkinson's disease (PD). The apolipoprotein E (APOE) allele epsilon 4 is a known risk factor for Alzheimer's disease and has also been suggested to be a risk factor for dementia in PD and even a predictor of impairment in certain cognitive domains. Methods: A total of 447 PD patients (PD patients without cognitive impairment: n = 187; PD patients with mild cognitive impairment: n = 188; PD patients with dementia: n = 72) were included from an ongoing observational German multicenter cohort study (LANDSCAPE study). All patients underwent an extensive neuropsychological test battery, including assessments of memory, visuospatial functioning, attention, language, and executive function. APOE genotype was determined by an allelic discrimination assay. Linear regression analysis was used to explore the associations between APOE-epsilon 4 and cognitive performance. Results: The APOE-epsilon 4 allele was not associated with a diagnosis of cognitive impairment in PD (PD with mild cognitive impairment and PD with dementia) or with deficits in specific neuropsychological domains in our study cohort. Conclusion: Our data question the relevance of the APOE-epsilon 4 allele as a predictor of cognitive impairment in PD. (C) 2016 Elsevier Ltd. All rights reserved.

Introduction: The relationship between freezing of gait (FOG) and postural instability in Parkinson's disease (PD) is unclear. We analyzed the impact of FOG on postural control. Methods: 31 PD patients with FOG (PD+FOG), 27 PD patients without FOG (PD-FOG) and 22 healthy control (HC) were assessed in the ON state. Postural control was measured with the Fullerton Advanced Balance (FAB) scale and with center of pressure (COP) analysis during quiet stance and maximal voluntary forward backward leaning. Results: The groups were balanced concerning age, disease duration and disease severity. PD+FOG performed significantly worse in the FAB scale (21.8 +/- 5.8) compared to PD-FOG (25.6 +/- 5.0) and HC (34.9 +/- 2.4) (mean +/- SD, p < 0.01). PD+FOG had impaired ability to voluntary lean forward, difficulties to stand on foam with eyes closed and reduced limits of stability compared to PD-FOG (p < 0.05). During quiet stance the average anterior posterior COP position was significantly displaced towards posterior in PD+FOG in comparison to PD-FOG and HC (p < 0.05). The COP position correlated with severity of FOG (p < 0.01). PD+FOG and PD-FOG did not differ in average COP sway excursion, sway velocity, sway regularity and postural control asymmetry. Conclusions: PD+FOG have reduced postural control compared to PD-FOG and HC. Our results show a relationship between the anterior posterior COP position during quiet stance and FOG. The COP shift towards posterior in PD+FOG leads to a restricted precondition to generate forward progression during gait initiation. This may contribute to the occurrence of FOG or might be a compensatory strategy to avoid forward falls. (C) 2015 Elsevier Ltd. All rights reserved.

Writers' cramp is a movement disorder with dystonic co-contraction of fingers and hand during writing and is part of the clinical spectrum of focal dystonias. Previous studies showed reduced striatal dopamine receptor D2 (DRD2) availability in dystonia. The expression of D2 receptors is modulated by a DRD2/ANKK1-Taq1A polymorphism (rs1800497). This study addresses the question of whether the DRD2/ANKK1-Taq1A polymorphism is a risk factor for writer's cramp. We determined the DRD2/ANKK1-Taq1A polymorphism 34 patients with writer's cramp compared to 67 age matched controls. 35.3\% of the patients and 31.3\% of our controls were assigned to the A1 genotype status (p = .7). Therefore DRD2/ANKK1-Taq1A gene is not a significant risk factor in the evolution of writer's cramp.

Background In an intensity difference limen paradigm in C57BL/6 mice, the sensitivity observed in an operant conditioning procedure was much larger than the sensitivity observed with a prepulse inhibition (PPI) procedure (Behrens & Klump 2015). Here, we compare the sensitivity of both procedures in a sound localization paradigm investigating, whether the sensitivity difference observed in an intensity difference limen paradigm may also be found in other paradigms. Methods The mice were presented with an acoustic background of repeated 100 ms noise stimuli broadcast from a reference speaker. At random times, one of the stimuli in the sequence was replaced by a stimulus that was broadcast from a test speaker located 12.5° to 180° apart from the reference speaker. Broadband (20 kHz bandwidth, 20 kHz center frequency) and narrowband (500 Hz bandwidth, 25 kHz center frequency) noise stimuli were presented in separate sessions. In the operant procedure, a Go/No-Go paradigm with food rewards was used and hit- and false-alarm rates served to calculate the sensitivity measure d’. In the PPI procedure, the movement of the mouse elicited by a 110 dB SPL startle stimulus (35 ms, 2-50 kHz) was measured using a piezo-electric pressure transducer. We applied an ROC analysis by comparing the distribution of startle amplitudes with a change in speaker location to that without such a change and calculated d(a) values, a sensitivity measure that corresponds to d’. Results For both procedures, the mean sensitivity measure increased with an increase of the angle between test and reference speaker. In the operant conditioning procedure, the sensitivity for large speaker separations reached d’-values of around 3.0 (broadband noise) and 2.0 (narrowband noise). The results obtained by the PPI procedure showed a much lower sensitivity, reaching da-values of 1.0 (broadband noise) and only 0.3 (narrowband noise). Conclusions The higher sensitivity observed in the operant procedure results in lower thresholds for localizing broadband noise than in the PPI procedure in which the subjects showed a lower sensitivity. The operant procedure also revealed a large sensitivity of C57BL/6 mice to localize narrowband noise stimuli, whereas in the PPI procedure the sensitivity was so low that no threshold could be determined. Thus, the operant procedure will allow obtaining measures of localization acuity when the PPI procedure fails. The observation of a higher sensitivity in operant conditioning procedures compared to PPI procedures appears to be a more general effect. Funding This study was funded by the DFG (TRR 31 and Cluster of Excellence “Hearing4all”)

Gerbils’ sound localization ability has extensively been tested under free-field stimulation (e.g., Heffner & Heffner, 1988; Maier & Klump, 2006; Carney et al., 2011; Lingner et al., 2012). While many neurophysiological studies use closedfield or near-field stimulation to present signals with interaural time and level differences (ITD and ILD, respectively), the gerbil’s behavioral sensitivity to ITD and ILD has so far only been derived from acoustic measurements (Maki & Furukawa, 2005) and free-field stimuli that favor the use of one or the other interaural cue (Lesica et al., 2012). Here we investigate the behavioral sensitivity of gerbils to ITD and ILD using freefield loudspeakers to mimic stimulation via headphones. Six Mongolian gerbils were trained in a left/right discrimination task using broadband noise stimuli presented from a loudspeaker array (-90° to +90°, minimum angle between loudspeakers 12°). Data collection under the so-called virtualheadphone stimulation started when animals reliably reached >95% correct responses for the outermost loudspeaker positions. Two loudspeakers in the array presented virtualheadphone stimuli using cross-talk cancellation in order to eliminate the undesired signal paths between the speakers and their respective contralateral ears. The cross-talk cancellation filters were based on head-related transfer functions measured prior to the experiments from a gerbil carcass. Stimuli were narrow-band noise bursts (bandwidth: 200 Hz, centre frequency: 0.75, 1, 2, 4, or 6 kHz, 60 dB SPL) to which either ITD (up to ±500 μs) or ILD (up to ±20 dB) were applied. Psychometric functions were derived from the animals’ responses and thresholds calculated at a sensitivity level corresponding to a d’ of 1. We found that all gerbils tested were able to lateralize sounds depending on the applied ITD or ILD. For stimuli with an ILD, reliable responses could be obtained for narrow-band noises with center frequencies ≥2 kHz. For stimuli with an ITD, reliable responses could be collected for center frequencies up to 2 kHz. Responses to stimuli with an ITD were cyclic indicating the use of phase information by the animals. The data will be discussed in terms of its applicability by comparing thresholds collected under virtual-headphone stimulation with data from free-field stimulation. Funding This study was funded by the DFG (TRR 31 and Cluster of Excellence “Hearing4all”).

Harmonicity is an important cue to group components of sounds from a specific source in the acoustic environment. If a component of a harmonic sound is slightly shifted in frequency, that tone becomes distinct from other harmonics components in a complex with a specific fundamental frequency. In a human psychophysical study, Klein-Hennig and colleagues (2012) determined masked thresholds for detecting a single component of a tone complex in relation to its mistuning and binaural phase by asking the subjects to report the presence of the target component presented at different sound levels. Unexpectedly, when adding masker harmonics outside the auditory filter tuned to the target frequency the masked threshold increased. This is in contrast to the expectation, that a higher number of components would make it easier to separate the complex from the target. To investigate the mechanisms underlying this observation, we recorded single- and multi-unit responses from inferior colliculus neurons of anesthetized gerbils that have been demonstrated to have a high sensitivity for detecting mistuning of components in a harmonic complex (e.g., Klinge-Strahl et al. 2013). Complex tone maskers were centered at the target frequency and either had 8 or 32 harmonic components equally distributed to both sides of the target. Maskers with two different phase relation between components were applied: random phase and sine phase maskers. Target tones were either tuned or mistuned with respect to the masker fundamental. Maskers were always played with the same phase to both ears. Targets of different levels were played either with the same phase or with a phase difference of 180 degrees between the two ears. Spike rate and temporal patterns of spike sequences (analysis with van Rossum [2001] metrics) were used to determine neuronal response thresholds. Neuronal sensitivity (da) was determined by subjecting the response measures to an ROC analysis comparing responses to masker plus target and masker alone. In general, an increased target level resulted in a higher da for both the rate response and the temporal spike pattern. Similar to the human psychophysical data (Klein-Hennig et al. 2012), the sensitivity for both response measures was considerably reduced in a fraction of the neurons if the bandwidth of the harmonic complex masker was increased. Also the phase relation of the masker components affected the response. However, the impact of mistuning and target phase was only small. The relation between the neurophysiological and the psychophysical data will be discussed. Funding This study was funded by the DFG (TRR 31 and Cluster of Excellence “Hearing4all”)

Acoustic multi-channel equalization techniques, such as the regularized partial multi-channel equalization technique based on the multiple-input/output inverse theorem (RP-MINT), are able to achieve a high dereverberation performance in the presence of room impulse response perturbations but may lead to additive noise amplification. This paper proposes to directly extend the RP-MINT technique by incorporating the noise statistics in the reshaping filter design, such that joint dereverberation and noise reduction is achieved. In addition to the regularization parameter used in the RP-MINT technique, a weighting parameter is introduced to trade off between dereverberation and noise reduction. To automatically determine the regularization and weighting parameters, a novel non-intrusive procedure based on the L-hypersurface is proposed. Simulation results using instrumental performance measures show that the proposed technique maintains the high dereverberation performance of the RP-MINT technique, while improving the noise reduction performance.

We consider the problem of blind multi-channel speech dereverberation without the knowledge of room acoustics. The dereverberated speech component is estimated by subtracting the undesired component, estimated using multi-channel linear prediction (MCLP), from the reference microphone signal. In this paper we present a framework for MCLP-based speech dereverberation by exploiting sparsity in the time-frequency domain. The presented framework uses a wideband or a narrowband signal model and a sparse analysis or synthesis model for the desired speech component. The proposed problems involving a reweighted $\ell_1$-norm, are solved in a flexible optimization framework. The obtained results are comparable to the state of the art, motivating further extensions exploiting sparsity and speech structure.

When deploying acoustic echo cancellation systems in large rooms, using short filters may result in significant amount of residual echo caused by room reverberation. In this paper, we model the late residual echo as exponentially decaying and use a parametric IIR filter to estimate its power in the subband domain for application in residual echo suppression. Working in an offline system identification setup, the problem of finding the optimal parameters of the IIR filter is addressed, with an analysis conducted on the performance of two parameter estimation methods: output error and equation error. The late residual echo power estimates obtained using the two methods are furthermore judged using the mean squared error and the mean squared log error cost functions. Results indicate that minimizing the mean squared log error for the output error method provides accurate estimates for the late residual echo power and the reverberation decay parameter.

In this paper we study the robustness of a recently proposed Multi-channel Wiener Filter-based speech dereverberation algorithm to errors in the assumed direction of arrival (DoA) of the target speech. Different subsets of microphones of a pair of behind-the-ear hearing aids are used to construct various monaural and binaural configurations of the algorithm. Via a simulation experiment with frontally positioned target it is shown, that when correct DoA is assumed binaural configurations of the algorithm almost double the improvement of PESQ measure over monaural configurations. However, in conditions where the assumed DoA is increasingly incorrect, the performance of the binaural configurations is shown to deteriorate more quickly than that of the monaural configurations. In effect, for large DoA errors it is the simpler, monaural configurations that perform better.

Blind adaptive identification of a Single-Input Multiple-Output (SIMO) acoustic system has useful applications including acoustic environment sensing, source localization and, in combination with multichannel equalization, dereverberation. An empirically chosen step-size is usually employed in blind system identification algorithms based on cross-relation error minimization. Although some adaptive step-size approaches have been proposed in the literature, the derivations rely, in some cases, on coarse approximations. In this paper, a locally optimal adaptive-step size exploiting the algebraic nature of the problem is derived. Experimental results using simulated room impulse responses show that the proposed algorithm has higher initial convergence rate.

With increasing complexity of hearing aids, the use of realistic and complex acoustic environments in the laboratory for hearing aid evaluation gains more and more attention. This contribution presents several listening scenarios relevant to hearing aid research that were defined for this purpose and rendered with a suitable virtual acoustics method. The scenarios vary in acoustic complexity and comprise in-door communication scenarios, in-door passive listening scenarios, and out-door environments, including public transport. Case studies using subsets of these scenarios are presented: Estimates of aided performance of different classes of hearing-aid algorithms using a virtual hearing aid, influence of source and receiver movement on beamformer performance, speech intelligibility measures using an international matrix test and evaluation of an auditory-based scene analysis algorithm. [Work funded by DFG FOR1732, SFB/TR31 and EXC 107

Introduction Speech perception in users of conventional cochlear implants (CI) degrades considerably in the presence of noise. Due to advances in surgical techniques, for a subgroup of CI candidates whose apical auditory nerves can still be stimulated acoustically, there is the possibility to preserve acoustic hearing even after implantation. Several clinical and vocoder studies reported on speech intelligibility benefits for electro-acoustic (EA-) listening condition in comparison with electric-only or acoustic-only conditions (termed EA-benefit) in these listeners. Goals of the study The goal of this study is to introduce an auditory model of speech intelligibility that can predict the EA-benefit. The model is used to assess the effect of different physiological factors on speech perception of electro-acoustic listeners. Methods Two different physiologically inspired auditory models are used to simulate the auditory nerve spiking pattern in response to electric and acoustic stimulation. The auditory model of Fredelake and Hohmann (2012) produces auditory nerve spikes in response to electric stimulation while the Meddis (2006) model simulates auditory nerve spikes in response to acoustic stimulation. Both spiking patterns were further processed by the central stage of the model of Fredelake and Hohmann (2012) to obtain internal representations of the stimuli, which may be present in the central part of the auditory system. The back-end of the proposed model consists of a standard GMM/ HMM speech recognition system. The internal representations were fed into the classifier and the recognition rate determined the predicted speech reception thresholds (SRTs) for sentences in stationary speech-shaped noise. Predicted SRTs were compared to SRTs measured in 22 patients equipped with Nucleus Hybrid-L device. Results The model predicted EA-benefit (SRT-difference between electric-only and electro-acoustic listening condition) of up to 3 dB, which agrees with the EA-benefit observed in most of the patients. Changing the amount of residual acoustic hearing in the model resulted in an EA-benefit even if the speech intelligibility with acoustic-only stimulation was close to chance, which is in line with the results of some of the patients. Increasing the amount of electric field spatial spread in the model increased SRTs both in electric-only and electroacoustic listening condition. Conclusion The model of speech intelligibility for electro-acoustic listeners can predict the EA-benefit that is observed in actual patients. The model has been used to assess the influence of different physiological parameters on speech reception thresholds and EA-benefit. Funding This work is supported by DFG cluster of excellence EXC 1077/1 "Hearing4All".

Die auditorische Bewegungswahrnehmung ist relativ unerforscht, insbesondere in akustisch sehr komplexen Situationen. In diesem Beitrag zeigen wir Ergebnisse aus ersten Studien zum Einfluss von Nachhall und Quellenanzahl auf die Bewegungswahrnehmung von normal- und schwerhörenden Probanden. Virtuelle Hörumgebungen wurden mittels eines Ambisonics-basierten Systems, das Simulationenmit hoher physikalischer Genauigkeit ermöglicht, erzeugt. Sowohl radiale (nah-fern) als auch laterale (links-rechts) Quellenbewegungenwurden untersucht. Natürliche Umgebungsgeräusche dienten als Testsignale. Die akustische Komplexität wurde durch Beifügen von stationären Quellen als auch Nachhall variiert. Zum Ausgleich der Hörbarkeit kam eine lineare Verstärkung zum Einsatz. Erwartungskonform zeigten die Analysen, dass Schwerhörende Quellenbewegungen schlechter wahrnehmen können als Normalhörende, jedoch nur unter akustisch komplexeren Bedingungen. Des Weiteren führte die Erhöhung der Quellenanzahl zu einer verminderten Detektierbarkeit von sowohl radialen als auch lateralen Bewegungen. Nachhall hatte lediglich einen Einfluss auf die Detektierbarkeit radialer Bewegungen, für die erhöhte Schwellen gemessen wurden. Zusammenfassend konnte mittels dieser Ergebnisse der Grundstein für Folgestudien gelegt werden, die sich mit dem Einfluss von Hörgerätesignalverarbeitung auf die auditorische Bewegungswahrnehmung befassen.

The amount of spatial release from masking is mainly determined by the change in interaural time difference (ITD) of the noise relative to the ITD of the signal. Accordingly, speech-in-noise with frontal speech presentation and noise from the front or back (S0N0 and S0N180 conditions) lead to similar detection and speech intelligibility thresholds. However, head movements can introduce dynamic binaural cues that may lead to a release from masking (RFM). In this study the effect of dynamic binaural cues on speech intelligibility was investigated for lowpass and highpass filtered signals to assess the influence of ITDs and interaural level differences (ILD). Movements were implemented as modulations of the nominal azimuths of the sound sources (S0N180, S0N0). These modulations were either in-phase or anti-phase for S and N. The stimuli were rendered using 11. order ambisonics with ’basic’ decoding, and presented via loudspeakers. Speech and noise signals were filtered at 1000 Hz (lowpass), 1500 Hz (highpass) or unfiltered. Results show a significant RFM with dynamic binaural cues for S0N0 in all filter conditions. For S0N180 only the unfiltered condition shows a significant RFM (funded by DFG FOR1732).

Die zunehmend komplexere Signalverarbeitung moderner digitaler Hörgeräte bietet zwar große Chancen für eine optimierte Versorgung, aber auch eine größer werdende Herausforderung für die effiziente individuelle Anpassung. Da bereits Patienten mit nur geringfügiger Schwerhörigkeit oder sogar Normalhörende von aktueller Hörgerätetechnologie profitieren können, spielt die effektive Wiedergabequalität eine immer größere Rolle. Sie kann nur über eine umfassende Evaluation neuer Hörsysteme mit einer Bewertung des erreichbaren Nutzens insbesondere in möglichst realitätsnahen Hörsituationen abgeschätzt werden. In dieser Studie werden dazu Methoden der virtuellen Akustik und ihr Einsatz in der Entwicklung und Bewertung eines akustisch transparenten Hörsystemprototyps vorgestellt. Dazu wurde eine Methode zum direkten virtuellen Vergleich von verschiedenen Kombinationen von Hardware- Bauformen und Signaloptimierung entwickelt. Für die virtuellen Testkonditionenwurden verschiedene alltagsrelevanteKonversationsszenen konzipiert und umgesetzt, die ein breites Spektrum verschiedener Signalqualitäten abdecken. Es konnte gezeigt werden, dass das neue transparente Hörsystem einen hohen Grad der Signalsteuerung ermöglicht und somit deutliche Vorteile gegenüber der klassischen Hörgerätesystemtechnik bietet. Das vorgestellte Hörsystem schafft so die Voraussetzungen für einen transparenten Klang, d.h. eine hohe individuelle Wiedergabequalität als Basis für neue Signalverarbeitungsstrategien.

Distanzwahrnehmung wird in der Regel mit dem Hallmaß (direct-toreverberant ratio, DRR) in Verbindung gebracht. Daher ist eine Interaktion von raumakustischen Simulationsmethoden und Distanzwahrnehmung zu erwarten. In dieser Studie wurde die Distanzwahrnehmung in einem realen Raum mit der Distanzwahrnehmung in einer einfachen Simulation desselben Raums verglichen. Dazu wurde ein Identifikations- Test verwendet, in dem die Versuchsteilnehmer fünf akustische Stimuli einer visuellen Darstellung von fünf Lautsprechern in unterschiedlichen Entfernungen zuordnen sollten. Die Stimuli unterschieden sich nur in der Aufnahmeposition. Die ”realen” Teststimuli wurden mit aufgenommenen kopfbezogenen Impulsantworten (HRIR) aus dem zu testenden Raum generiert. Die simulierten Stimuli wurdenmit reflexionsarmen HRIR und einer Raumakustiksimulation erzeugt. Für die Raumakustiksimulation wurde ein Werkzeug genutzt, welches auf zeitvariante Simulationen für Anwendungen in der Audiologie optimiert ist. Frühe Reflexionen werden mit einem geometrischen Spiegelschallquellenmodell nachgebildet, später Nachhall wird über positionsunabhängigen Faltungshall hinzugefügt. Unterschiedliche Einstellungen des Spiegelschallquellenmodells und des Übergangs von frühen Reflexionen zu spätem Hall wurden untersucht. Die subjektiven Ergebnisse wurden mit etablierten Raumakustikmaßen wie DRR, IACC und T60 verglichen. Die Ergebnisse zeigen, dass die verwendete effiziente Simulationsmethode bei geeigneter Parametrisierung eine natürliche Distanzwahrnehmung ähnlich wie in realen Räumen erreichen kann.

Die Lautheit von Musik wird von vielen Menschen ganz unterschiedlich wahrgenommen. Neben der physikalischen Komplexität des vielfältigen Klangszenarios von Musik ist vor allem die Verwechselung zwischen Lautheit und Präferenz eine Ursache für die Schwankung in der Beurteilung. Diese Schwierigkeit führt dazu, dass in der Anwendung bspw. bei Fernsehen und Rundfunk immer noch Pegelmaße Lautheitsmodellen vorgezogen werden, und weiter dass diese physiologisch motivierten, jedoch nur an Rauschen und Sinuston entwickelten Lautheitsmodelle nur schwerlich für diese Herausforderung modifiziert werden können. Der Paarvergleich ist eine geeignete Methode, um die Schwierigkeit der Beurteilung zu reduzieren, da den Versuchspersonen die Einordnung der wahrgenommenen Lautheit in einer absoluten Skala erspart bleibt. Mithilfe des Bradley-Terry-Luce Verfahrens für die Paarvergleichsauswertung lassen sich dann nicht nur Aussagen über die Rangfolge der verglichenen Musikstücke treffen, sondern auch quantitativ über Lautheitsverhältnisse. Wie gut können die Modelle einen Pool an Musikstücken nach Lautheit sortieren und wie gut deren Lautheitsverhältnisse zueinander schätzen? So können nun verschiedene Lautheitsmodelle qualitativ bewertet und darüber hinaus Stärken, Schwächen und Modifizierungen aufgezeigt werden. Die bisherigen Ergebnisse zeigen, dass sich in der Qualität der Darstellung der Rangfolge Pegelmaße und Lautheitsmodelle kaum unterscheiden. Dagegen treten bei der Darstellung der Verhältniswerte interessante Unterschiede auf, welche Ansätze zu Modifizierungen von Lautheitsmodellen liefern.

In the context of localization for Computational Auditory Scene Analysis (CASA), probabilistic localization is a technique where a probability that a sound source is present is computed for each possible direction. This approach has been shown to work well with artificial head signals provided the location of the sources to be localized is in front of the user and approximately on the same plane as the ears. Modern hearing aids use multiple microphones to perform array processing, and in a bilateral configuration, the extra microphones can be used by localization algorithms to not only estimate the horizontal direction (azimuth), but vertical direction (elevation) as well, thereby also resolving the front-back confusion. In this work, we present three different approaches to use Gaussian Mixture Model classifiers to localize sounds relative to a multi-microphone bilateral hearing aid. One approach is to divide a unit sphere into a nonuniform grid and assign a class to each grid point; the other two approaches estimate elevation and azimuth separately, using either a verticalpolar coordinate system or an ear-polar coordinate system. The benefits and drawbacks in terms of performance, computational complexity and memory requirements are discussed for each of these approaches.

Bei der Beurteilung der Güte eines Fahrzeuggeräuschs durch psychoakustische Laien bzw. NutzerInnen wird in der Regel Bezug auf Attribute wie z.B. ”sportlich” oder ”komfortabel” und die An- oder Abwesenheit von störenden Geräuschelementen genommen. Im Prozess der Geräuschanalyse und des Sounddesigns stellen jedoch geräuschbeschreibende, psychoakustische Messgrößen wie z.B. Lautheit, Tonhaltigkeit, Rauigkeit und Impulshaftigkeit ein wichtiges Analysetool zur Geräuschcharakterisierung dar. Die Optimierung eines Fahrzeuggeräuschs zur adäquaten Positionierung des Fahrzeugs auf dem Markt profitiert stark von Kenntnissen über die Verbindung zwischen diesen psychoakustischen Geräuschcharakteristika und den dem Geräusch zugeordneten Attributen. Durch gezielte Variation verschiedener Geräuschcharakteristika mit Geräuschsynthesesystemen direkt im Fahrversuch und bei Hörexperimenten im Labor werden Geräuscheigenschaften mit subjektiv wahrgenommenen Eindrücken verknüpft. Hierbei kann die subjektive Bewertung einer Größe jedoch , bedingt z.B. durch für Fahrzeuggeräusche typische Eigenschaften wie stochastische Modulationen oder sich zeitlich schnell verändernde Geräuschkomponenten, stark von der Berechnung der Messgröße durch Analysealgorithmen abweichen. Es werden Ergebnisse aus Fahr- und Laborversuchen sowie neu entwickelte Methoden zur Berechnung psychoakustischer Messgrößen vorgestellt. Durch deren erhöhte Berechnungssicherheit können nun belastbarere Aussagen über Zusammenhänge zwischen Subjektivurteilen und modellhaft berechneten Geräuschattributen gemacht werden.

Das binaurale Hören ermöglicht dem Menschen neben der Lokalisation auch die Ausrichtung einer direktiven Schallquelle anzugeben. In einem Hörversuch wurde die wahrgenommene Ausrichtung eines Lautsprechers in einem Raum experimentell bestimmt. Der Lautsprecher drehte sich einmal um die Mittelachse am physikalischen Schwerpunkt und einmal um das akustische Zentrum nahe der Membran. Bei der Rotation um das akustische Zentrum sollte die Quellposition gleich bleiben. Bei einer Rotation um die Mittelachse ist eine stabile Quellposition nicht gegeben. In diesem Beitrag soll gezeigt werden, dass die Wahl der Rotationsachse der direktiven Schallquelle die wahrgenommeneQuellausrichtung beeinflusst. Besonders für Lautsprecherausrichtungen im vorderen Bereich (±90◦), bei dem der Lautsprecher dem Zuhörer zugewandt ist, unterscheiden sich die Probandenurteile zwischen den beiden Rotationsachsen. Bei einer Rotation um die Mittelachse ist der Winkel der wahrgenommenen Ausrichtung größer als der ermittelte Winkel bei einer Drehung um das akustische Zentrum. Eine mögliche Ursache könnte die zusätzliche Information einer Quellpositionsverschiebung, verursacht durch interaurale Pegel- und Laufzeitunterschiede beim Hörenden, sein.

The ability to localize sound sources in reverberant environments is dependent upon first-arriving information, an outcome commonly termed ”the precedence effect”. For example, in laboratory experiments, the combination of a leading (direct) sound followed by a lagging (reflected) sound is localized in the direction of the leading sound. This study was designed to measure the degree to which the interaural coherence of leading and lagging sounds, respectively, affected performance. The coherence of leading or lagging sounds was varied by either presenting a sound from a single loudspeaker or by presenting mutually uncorrelated versions of sounds from 5 adjacent loudspeakers. The listener’s task was to point to the perceived location of leading and lagging sources of sounds which were 10-ms long, low-pass filtered white noises, or 2- second long tokens of speech. The leading and lagging stimuli were presented either from speakers located directly in front of them or from speakers located +/- 45◦ to the right or left. The results indicate that leading coherent sounds influence perceived location more so than do leading incoherent sounds. This was true independent of whether sounds were Gaußian noises or tokens of speech.

When sound is reproduced inside a room, both ears receive different spectral content. It can be assumed that the brain uses this different spectral information arriving at each ear to balance spectral deviations over the frequencies associated with coloration. This effect is known as binaural decoloration. To investigate this effect more closely, simplified spectral shapes can be used to get insight into the underling process. In this contribution spectral shapes are designed to fluctuate with a constant rate on the ERB rate scale. To get a dichotic presentation, both ears receive the contrary spectral shape. While the energy increases in one ear, it decreases at the other ear and vice versa in a frequencydependentmanner. A listening test is conducted in order to measure the threshold for these spectral modifications to result in an unnatural sound. It is discussed whether the effect of binaural decoloration depends on the rate of this spectral manipulation.

Psychoacoustic roughness, which can occur for example in sounds of rotating machinery and speech, can have influence on different sound quality aspects such as the perceived pleasantness. Therefore, roughness has relevance in the context of product sound design, e.g. for vehicle interior sounds. Roughness arises from amplitude modulations within the frequency range of about 15 to 150 Hz. Due to variations of such modulations over time, roughness can vary over time, for example when a car is accelerating. So far, roughness perception has rarely been studied with a focus on such temporal changes. One may question whether there exists a temporal build-up for the strength of perceived subjective roughness. In the present study, a roughness matching experiment for stimuli containing amplitude modulated parts with different lengths was conducted. It was found that the amount of perceived overall roughness seems to increase with increasing duration of the rough portion inside a sound with fixed overall length. From this, a general trend for changes in roughness perceptionwith such time-changes has been found and a model describing these changes will be presented.

In multichannel audio reproduction it is usually desired to create a listening experience that is as authentic as possible with respect to the spatial impression. Recently, a newmultichannel audio reproduction system and optimization method was introduced by Grosse and van de Par [IEEE, (2015)], that is used for a perceptual accurate reproduction of recorded sound fields. Basis for this are separately recorded signals that represent the direct and diffuse sound field. In order to minimize the perceptual relevant influences in the reproduction room, the optimization method takes care of the spectral aspects of those signals. To generalize the proposed method, existing stereo recordings are processed in such a way that they can be used for the above-mentioned reproduction system. For this purpose an algorithm for signal separation that has been presented by Breebaart and Schuijers [IEEE, (2008)] is used to decompose a stereo signal into a direct and diffuse signal. These signals are used in the perceptually motivated optimization method as well. A subjective evaluation is conducted to show the improvement of the perceived quality of such an approach.

The simulation of room acoustics for auralization can have numerous applications in interactive evaluation environments (e.g., for hearing aid development), psychoacoustic studies with adaptively changing roomreverberation, or simulation, rehabilitation, and computer games. A fast and perceptually plausible method for synthesizing binaural room impulse responses (BRIR) [Wendt et al., J. Audio Eng. Soc., 62, 11 (2014)] has been extended to simulate the acoustics of multiple coupled rooms, that are acoustically connected by doors or wall openings. As for the single-room simulation method, computational efficiency is achieved by using a hybrid approach, where the early reflections are calculated as image sources up to a low order and the reverberation is generated by efficient feedback delay networks [FDN; Jot and Chaigne, Proc. 90th AES Conv. (1991)]. The binaurally extended FDNs are designed to account for the reverberation properties of coupled rooms, as well as for the spatial distribution of reverberation in the respective rooms, including the vicinity of the room connections. The suggested BRIR synthesis method was evaluated by comparing measured and synthesized BRIRs for connected rooms differing in size and reverberation time using technical measures and subjective listening tests.

In der sogenannten Cocktail-Party-Situation sprechen meistens mehrere Personen durcheinander, aber als Zuhörer verfolgt man in der Regel zu jedem Zeitpunkt nur einen dieser Sprecher. Für die Wahrung einer angenehmen und natürlichen Hörsituation unter solchen Umständen ist neben guter Sprachverständlichkeit des Zielsprechers auch der korrekte räumliche Eindruck der gesamten akustischen Szene wichtig. Ein den Hörer unterstützender Hörgerätealgorithmus sollte daher sowohl den Signal-Rausch-Abstand (SNR) zwischen Zielsprecher und dem Störgeräusch verbessern als auch möglichst die binaurale Information vollständig erhalten. Der von Hadad et al. (2012) vorgeschlagene Binaural Linearly ConstrainedMinimum Variance (BLCMV) Beamformer verspricht, beide Ziele zu einem hohen Maße zu erreichen. In dieser Studie wurde das Verhalten des BLCMV-Beamformers für verschiedene Optimierungen des Algorithmus instrumentell untersucht. Basierend auf den gefundenenVeränderungen der binauralen Signaleigenschaften wurden künstliche Signale generiert und zusammen mit den vom Beamformer direkt verarbeiteten Signalen von 10 Probanden evaluiert. Hierbei wurden Sprachverständlichkeit, Lokalisation und Höranstrengung bewertet. Es zeigt sich, dass der SNR der dominierende Faktor für Sprachverständlichkeit und Höranstrengung ist. In den Experimenten zur Lokalisation zeigte sich allerdings, dass die Optimierung mit der stärksten SNR-Verbesserung zu einer deutlichen Verfälschung des räumlichen Eindrucks führte. Diese Ergebnisse zusammenfassend wird eine Kompromisseinstellung vorgeschlagen, die bei geringfügig kleinerer SNR-Verbesserung eine möglichst große Räumlichkeit bewahrt.

Bei der Darbietung von Kopfhörersignalen kann es wünschenswert sein, eine möglichst realistische Hörsituation eines Schallereignisses zu simulieren. Neben einer bestimmten Einfallsrichtung und Distanz sollte das Schallereignis außerhalb des Kopfes wahrgenommen werden. Jedoch ist es nicht immermöglich bei der Generierung der Kopfhörersignale die dafür notwendigen individuellenAußenohrübertragungsfunktionen zu berücksichtigen und das Kopfhörersignal individuell zu entzerren. Für diesen Beitrag wurden in psychoakustischen Experimenten untersucht, welchen Einfluss ein zusätzlicher visueller Stimulus auf die Wahrnehmung eines Schallereignisses hat. Dafür wurde die wahrgenommeneDistanz von sechs Entfernungen zwischen 0.9 m bis 4.9 m variiert und der Grad der Externalisierung für 24 Einfallsrichtungen in 15 Grad Schritten bei einer Entfernung von 1.4 m ermittelt. Die visuelle Darbietung erfolgte auf einem 3D-Monitor mit aktivierter und deaktivierter 3D-Funktion und mit der Virtual Reality Brille Oculus Rift. Eine weitere Kondition, ohne visuelle Darbietung, diente als Referenz. Die akustischen Stimuli wurden durch Binauralsynthese mit binauralen Raumimpulsantworten eines Kunstkopfes generiert. Die zusätzliche visuelle Darbietung zeigt keinen signifikanten Einfluss auf den Grad der Externalisierung. Allerdings scheinen die Ergebnisse des Distanzexperiments durch die visuelle Darbietung beeinflusst zu werden. Im Vergleich zur Referenzkondition ohne visueller Darbietung zeigt sich eine systematische Überschätzung der Distanz.

Wie in vielen Bereichen unseres Alltags wachsen auch im Pkw-Bereich die Ansprüche der Nutzer. Neben Fahreigenschaften und finanziellen Aspekten rücken zunehmend auch Umweltaspekte wie z.B. Lärmbelastung in den Fokus. Neben der Belastung durch Lärm haben die Fahrgeräusche für viele Menschen aber eine viel weitreichendere Bedeutung: sie sind Träger von Informationen, sie sind die ”Sprache” des Fahrzeugs, sie können sogar Emotionen auslösen. Die Wirkung der Fahrgeräusche eines Fahrzeugs auf eine Person kann aber ganz unterschiedlich ausfallen, je nachdem in welchem Kontext das Gehörte steht, so z.B. die Beziehung der Person zum Fahrzeug, die Situation, in der sie die Geräusche erlebt, aber sicherlich auch ihre individuelle Einstellung zu Fahrgeräuschen: persönliche Vorlieben und damit verbundene Erwartungen und Ansprüche an das Fahrgeräusch sind moderierende Faktoren bei der Beurteilung von Fahrgeräuschen. In diesem Beitrag werden die Ergebnisse einer Befragung dargestellt, in der die Einstellung der Teilnehmer zum Thema Fahrzeuggeräusche sowie ihre Beurteilung der bzw. Wünsche an die Geräusche des eigenen Fahrzeugs erfasst wurden. Anhand der Ergebnisse einer großen Stichprobe von Fahrzeugkunden aus dem Premium-Segment wurde eine Typisierung vorgenommen, um damit einen Ansatzpunkt für weitere Analysen der individuellen Einflüsse auf die Beurteilung von Fahrgeräuschen zu schaffen. Die Ergebnisse deuten auf drei unterschiedliche ”Fahrzeugsound”-Typen hin.

In diesem Beitrag behandeln wir die Fragewelchen Klangcharakter ein Fahrzeug aufweisen muss um positiv wahrgenommen zu werden. Dabei ist ein zentraler Aspekt, ob es interindividuelle Unterschiede in der Wahrnehmung des Fahrgeräusches gibt, und wie die Reaktion des Fahrers ausfällt wenn der Klangcharakter des Fahrzeuges nicht mit seiner Erwartung übereinstimmt. In der hier vorgestellten Studie wurden diese Fragen in holistischerWeise betrachtet. Bei der als Feldexperiment ausgelegten Blindstudie fuhren 20 Probanden eine Limousine der oberen Mittelklasse jeweils dreimal zur Probe, wobei bei zwei Fahrten der Fahrzeugklang durch einen elektroakustischen Soundgenerator modifiziert wurde. Die Probanden wurden instruiert während der Fahrt all ihre Gedanken zum Fahrgeräusch laut zu äußern. Die Probanden wurden im weiteren Verlauf gebeten eine globale bzw. auf die Faktoren Komfort und Sportlichkeit bezogene Bewertung des Fahrgeräusches abzugeben. Durch die Gestaltung als Leitfadeninterview wurden auch qualitative Aspekte der Wahrnehmung des Fahrgeräusches miterfasst. Am Ende der Testfahrt wurden die Probanden gebeten einen Fragebogen zu Persönlichkeitsfaktoren, ihrer Einstellung zu Lärm sowie ihrer Einstellung zu Fahrzeugen auszufüllen. Darüber hinaus wurde die implizite Einstellung der Probanden zu Statussymbolen abgefragt. Die vorliegende Publikation präsentiert die zentralen Ergebnisse dieser Studie und diskutiert deren Implikationen.

The Perception of spaciousness in rooms is depending on the reflections of the sound at the walls. Especially the strength of the reflections at the side walls are often assumed to be important for the perception of source width and envelopment. This study shows the results of a psychoacoustic experiment, where the perception of source width and envelopment had to be rated by subjects. The stimuli were anechoic music signals convolved with binaural room impulse responses (BRIR) and were presented with headphones. The BRIRs were either recordings of real rooms or simulated with a mirror image model. The simulation of BRIRs allowed to alter the absorption coefficients of the side walls separately from the other surfaces of the room. By systematically varying the strength of the side reflections within the room, the dependency of the perception of spaciousness on lateral fraction was investigated. The resulting subjective ratings of the stimuli are compared to subjective ratings of stimuli gained by direct manipulations of the interaural crosscorrelation of BRIRs. In this way we can compare the influence of side reflections on the perception of source width and envelopment to the influence of interaural cross-correlation.

This paper presents a system for acoustic scene classification (SC) that is applied to data of the SC task of the DCASE’16 challenge (Task 1). The proposed method is based on extracting acoustic features that employ a relatively long temporal context, i.e., amplitude modulation filer bank (AMFB) features, prior to detection of acoustic scenes using a neural network (NN) based classification approach. Recurrent neural networks (RNN) are well suited to model long-term acoustic dependencies that are known to encode important information for SC tasks. However, RNNs require a relatively large amount of training data in comparison to feed-forward deep neural networks (DNNs). Hence, the time-delay neural network (TDNN) approach is used in the present work that enables analysis of long contextual information similar to RNNs but with training efforts comparable to conventional DNNs. The proposed SC system attains a recognition accuracy of 76.5 %, which is 4.0 % higher compared to the DCASE’16 baseline system.

# Introduction # How well should the various audiological findings best be represented and how can this information be used to characterize the individual hearing problem of each patient – preferably in a way which is independent from his or her native language? This contribution reviews the approach and models developed in the Cluster of Excellence Hearing4All (Oldenburg/Hannover) to unite the diverse audiological databases, e.g. from the hearing research and clinical institutions in Oldenburg and in Hannover in a more abstract, comprehensive way than the previously defined “auditory profiles”. # Method # A set of “common audiological functional parameters” (CAFPAs) has been defined that serves as an abstract representation of the most important audiological characteristics of each patient. The CAFPAs include, e.g., sensitivity loss in different frequency regions, distortion component and compression loss at low and high frequencies, central and binaural loss, cognitive and socio-economic component of the hearing loss. These CAFPAs have been defined in order to make non-consistent and non-complete audiological data accessible for methods of machine learning, such as, e.g. Bayesian nets. Since speech recognition tests in noise are the most crucial outcome parameter, the multilingual matrix test (Kollmeier et al., 2015 Int. J. Audiol. online first) is used which is suitable not only for comparisons across different clinics but also across languages. The individual Speech Recognition Thresholds (SRT) in stationary and in fluctuating noise were predicted using the audiogram and an estimate of the internal level uncertainty as parameters following the Automatic Speech Recognition (ASR) approach by Schädler et al. (2015, Int. J. Audiol. Online first) # Results # Using such statistical methods, a data-driven audiological classification for different classes of hearing loss becomes possible. Estimates of the “typical” hearing loss and suprathreshold distortion components in combination with ASR-based speech recognition prediction allow to predict the individual performance for the closed-set Matrix sentence recognition test in different languages. # Conclusions # A consistency check across the different audiological input and outcome measures becomes possible by using auditory models adapted to the individual hearing impairment. The concept of a more abstract representation of audiological diagnostical information in combination with speech recognition prediction methods and other machine learning approaches appears to be promising for further research in diagnostical and rehabilitative audiology. # Funding# DFG, EXC 1077 Hearing4All

For normal hearing listeners, sound localization in the frontal azimuthal half-plane is primarily achieved by neural processing of interaural differences in level and arrival time. While interaural level differences are to some extent also used by bilateral cochlear implant (CI) subjects, encoding of perceptually exploitable interaural time differences (ITDs) by pulse timing is still a topic of ongoing research. The current study is motivated by the fact that CI subjects are able to exploit ITDs when presented with fully synchronized low-rate pulse trains. In the first part of the study, extent of lateralization for fixed ITDs of up to 3 ms was measured in normal-hearing subjects. Stimuli were either unfiltered or 3-5 kHz band pass filtered click trains, the latter mimicking the perception of CI users, i.e. the absence of any low-frequency temporal fine-structure information. Results indicate that, while unfiltered click trains of 600 μs ITD (corresponding to almost 90° in free-field listening) were lateralized at the ear, filtered click-trains required approximately 1.0-1.4 ms ITD for equally strong lateralization, at least in some subjects. In the second part of this study, lateralization of low-rate pulse trains was measured using single electrode stimulation in bilateral CI subjects. For the subjects tested so far with the constant rate and constant level pulse trains, a change in lateralization percept with changing ITD could only be measured at rates lower than 200 pulses per second (pps). On average, an ITD of 1.0 ms was required to lateralize the pulse train at the ear. The results indicate that, if the speech coding allows for sufficiently low pulse rates, ITD enhancement may be beneficial in future binaural CIs to provide improved localization performance. The rate limit of 100-200 pps is, however, even lower than for ITD detection. The results have inspired the development of a signal processing algorithm specific for binaural CIs. Ongoing research is evaluating sound localization performance and speech intelligibility with this new algorithm. # Funding # This work was funded by European Union under the Advancing Binaural Cochlear Implant Technology (ABCIT) grant agreement (No. 304912) and by the DFG Cluster of Excellence Hearing4all.

Introduction Which information is needed to complement the pure tone audiogram in order to accurately predict speech reception thresholds (SRTs) in noise for listeners with impaired hearing? To answer this question, a framework which is able to simulate speech recognition in noise of listeners with normal hearing and accurately predict reference-free SRTs in several noise conditions (Schädler et al., in press) was enhanced to perform simulations for listeners with impaired hearing. Method Reference-free, i.e. not depending on any reference measurement, SRTs were predicted by simulating the German matrix sentence test (Wagener et al. 1999) with an individually adapted automatic speech recognition (ASR) system. In a first experiment, the effect of the absolute hearing thresholds, determined from 200 individual audiograms, was implemented into the feature extraction stage of the ASR system. The recognition results were compared to empirical data and speech intelligibility index (SII) based predictions form the literature. For a second experiment, in extension to the pure tone audiogram based simulations, a suprathreshold deficiency, modelled by a level uncertainty uL in the feature extraction stage of the ASR system, is postulated. The values for the individual supra-threshold deficiency uL were determined from the respective other noise condition by choosing uL to match the empirical and predicted SRTs. Results The results show that the loss of sensitivity described by the individual pure tone threshold explains only 40% of the empirically observed variance in a stationary and 50% in a fluctuating noise condition. Taking into account pure tone threshold and individual supra-threshold hearing deficiency, 67% and 76% of the empirically observed variance can be explained in the stationary and the fluctuating noise condition, respectively. Conclusions The study concludes that the individual audiogram describes the impaired hearing incompletely and should be complemented with a description of individual supra-threshold hearing deficiencies to improve the prediction accuracy. The accurate simulation of human speech recognition, using suboptimal signal processing in order to model impaired hearing, could enable simulations under aided conditions. The suitability of this approach for aided performance prediction should be assessed in future work. Funding This work was supported by the Deutsche Forschungsgemeinschaft SFB/TRR 31 “The active auditory system” and the Cluster of Excellence Grant “Hearing4all”.

Introduction The difficulty of understanding speech in noisy environments is not very well reflected by pure tone audiogram findings. To better understand a patient’s problem, it is necessary to assess his or her communication ability in noisy environments. This might also help to assess possible supra-threshold distortions that occur in the auditory system as a result of hearing impairment, independent from the sensitivity loss assessed by the tone audiogram or speech audiometry in quiet. Hence, speech recognition tests in noise have become more and more important in audiological diagnostics in recent years. So-called ‘matrix sentence tests’ use a closedset format and comprise syntactically fixed, semantically unpredictable sentences (e.g. “Peter kept two green toys”). Providing a vocabulary of only 50 words (10 alternatives for each position in the sentence), matrix sentence tests are suitable for speech perception testing without losing the usability for repeated speech perception testing with the same patient. In a multilingual society where each patient should be tested with her or his native language, experimenters that do not understand the test language may still supervise the test if its closed-set response format is used. Meanwhile matrix sentences tests developed according to common minimum quality standards for speech intelligibility tests are available for 15 different languages (i.e., in Swedish, German, Danish, Dutch, American English, British English, French, Polish, Turkish, Spanish, Italian, Persian, Arabian, Finnish, and Russian) together with a varying degree of supportive data. The common quality standards result in a high homogeneity of the speech materials and test lists employed what yields steep test-specific intelligibility functions and high test efficiency. Methods This contribution presents matrix sentence test data of two multi-center studies in the USA and Russia investigating the different influence of hearing ability on the SRT in quiet and noise. Data include adaptively estimated speech reception thresholds (SRTs), i.e. the sound pressure levels or signal-tonoise ratios (SNR) yielding 50% speech intelligibility, as well as correlations between hearing ability and SRT. Results The common quality standards applied during their development resulted in efficient and reliable tests with high comparability across the languages. Data emphasize the high potential of matrix sentence tests to disentangle the contribution of possible supra-threshold distortions to a certain hearing loss from that of the pure loss in sensitivity. Conclusions The Matrix test format has been shown as a sensitive diagnostic tool suitable for multilingual comparisons. Funding DFG, Cluster of Excellence 1077 Hearing4All

The relative contribution of sensory, bottom-up processing and cognitive, top-down processing in speech comprehension is influenced by external factors (like linguistic complexity, interfering noise, and reverberation) and internal factors (like age, hearing loss, and cognitive abilities of the listener). A review is given on joint studies from audiology and linguistics to characterize these factors. The studies to be presented in more detail obtained speech recognition in noise and/or reverberation in younger (YNH) and older listeners (ONH) with normal hearing, and in older hearing-impaired listeners (OHI). For YNH and ONH, a combination of age, SNR, vocabulary size, and lexical access time predicted speech recognition scores. OHI required more favorable SNR to reach the same performance than the age-matched ONH even when speech was presented with NAL-R amplification to (partially) compensate for their sensory deficits. Whereas vocabulary size was unchanged and lexical access time was increased both for ONH and OHI, working memory slightly decreased only for OHI. This provides evidence for the importance of non-auditory cognitive measures (like a specific combination of vocabulary size, lexical access time, and working memory) in explaining the comparatively poorer speech recognition scores that are observed for older vs. younger listeners and for OHI vs. ONH.

This study investigates the effect of noise and reverberation on speech recognition for an open- and a closed-set sentence test. While both tests yield approximately the same recognition threshold in trained normalhearing listeners, their performance may differ due to cognitive factors, i.e., the closed-set test is more sensitive to training effects while the open-set test is more affected by language familiarity. The experimental data were compared to predictions of the speech transmission index as a measure of pure acoustic effects. The largest differences between the open- and closed-set speech tests were measured in reverberation indicating a considerable influence of non-acoustic, cognitive factors. The recognition scores were on average 50% higher for the closed-set test with syntactically fixed and semantically unpredictable sentences than for the open-set test consisting of everyday sentences. To examine the underlying reasons, the closed-set test was presented to naïve listeners, with no training prior the measurements and no information about the test’s structure. Removing this information, the differences between the tests were not present indicating that the degree of familiarity with the speech material has a major impact on speech recognition. This indicates a strong cognitive factor which cannot be predicted by the speech transmission index.

Project aims at providing an audio signal presentationwhich is optimized to the individual preference and any hearing impairment in a situation and presentation-material-aware way. Previous studies have shown that individual listening preferences, although quite stable within subjects, differed markedly across the group. Therefore, in the present study, to find out possible sources of variability, subjects with normal or slightly impaired hearing are selected according to three factors: age, speech intelligibility performance and audiogram, and assigned to test groups so that - within each group - subjects differ in only one of the factors. Each person performs a battery of tests using speech stimuli in noise and quiet. In the first set of experiments, the reaction to very basic signal modifications such as broadband gain, equalization, allowed amount of artifacts due to dynamic range compression or clipping is assessed to optimize the presentation mode to each individual. The second part assesses preferred processing schemes of a complex speech enhancement algorithm together with the benefit of such enhancement. This systematic data base will be used to investigate if basic individual factors are related to listening preferences and if preferences with respect to simple signal modifications generalize to more complex processing schemes.

In der Psychoakustik sind Rauigkeit, Schärfe, Tonhaltigkeit und Lautheit gängige Maße zur Bewertung von Geräuschen. In Studien mit Probanden wird in der Regel immer nur eines der Maße bewertet, z.B. um eine Berechnungsvorschrift für das jeweilige Maß abzuleiten. Eine Methode für die Vorhersage der Klangqualität von Geräuschen ist die Kombination dieser Maße zu einem Gesamturteil, z.B. Lästigkeit. Hierfür wird meist nur das Gesamturteil mit Probanden subjektiv gemessen und die zu kombinierenden Maße werden berechnet. Es fehlen somit subjektive Daten, die sowohl die verschiedenen psychoakustischen Maße als auch das Gesamturteil für eine Auswahl von Geräuschen beinhalten. In diesem Beitrag wird eine Methode vorgestellt und validiert, in der die psychoakustischen Maße Rauigkeit, Schärfe, Tonhaltigkeit und Lautheit gleichzeitig mit Lästigkeit als Gesamturteil subjektiv bewertet werden. Für eine einfache Anwendung soll die Methode eine Bewertung von vielen Geräuschen in kurzer Zeit mit untrainierten Probanden ermöglichen. Die Ergebnisse zeigen, dass die Probanden in Test/Re-Test-Messungen zu gut reproduzierbaren Ergebnissen kommen. Die absoluten Bewertungen werden vom experimentellen Kontext, insbesondere der Geräuschauswahl, beeinflusst. Die relativen Bewertungen sind jedoch gut reproduzierbar.

Die zunehmend komplexere Signalverarbeitung moderner digitaler Hörgeräte bietet zwar große Chancen für eine optimierte Versorgung, aber auch eine größer werdende Herausforderung für die effiziente individuelle Anpassung. Da bereits Patienten mit nur geringfügiger Schwerhörigkeit oder sogar Normalhörende von aktueller Hörgerätetechnologie profitieren können, spielt die effektive Wiedergabequalität eine immer größere Rolle. Sie kann nur über eine umfassende Evaluation neuer Hörsysteme mit einer Bewertung des erreichbaren Nutzens insbesondere in möglichst realitätsnahen Hörsituationen abgeschätzt werden. In dieser Studie werden dazu Methoden der virtuellen Akustik und ihr Einsatz in der Entwicklung und Bewertung eines akustisch transparenten Hörsystemprototyps vorgestellt. Dazu wurde eine Methode zum direkten virtuellen Vergleich von verschiedenen Kombinationen von Hardware- Bauformen und Signaloptimierung entwickelt. Für die virtuellen Testkonditionenwurden verschiedene alltagsrelevanteKonversationsszenen konzipiert und umgesetzt, die ein breites Spektrum verschiedener Signalqualitäten abdecken. Es konnte gezeigt werden, dass das neue transparente Hörsystem einen hohen Grad der Signalsteuerung ermöglicht und somit deutliche Vorteile gegenüber der klassischen Hörgerätesystemtechnik bietet. Das vorgestellte Hörsystem schafft so die Voraussetzungen für einen transparenten Klang, d.h. eine hohe individuelle Wiedergabequalität als Basis für neue Signalverarbeitungsstrategien.

Background The auditory brainstem response (ABR) is an evoked potential that reflects the responses to sound by the brainstem neural centers. The binaural interaction component (BIC) is obtained by subtracting the sum of the monaural ABR responses from the binaural response. It is assumed to represent the activity of binaural nuclei (Jewett, 1970, Electroencephalogr. Clin. Neurophysiol. 28: 609–618). The amplitude and latency of the BIC are dependent on the binaural cues presented (Furst et al., 1990, Hear. Res. 187: 63–72). The BIC can be used to non-invasively test binaural processing. However, any conclusions are limited by the lack of knowledge of the relevant processes at the level of individual neurons. The aim of this study is to characterize the ABR and BIC in the barn owl, an animal where the ITD-processing neural circuits have been extensively studied. Methods ABRs were measured in 9 adult barn owls. Responses to chirps at different levels and ITDs were recorded, and the BIC was derived as a function of ITD. To determine the extent of the crosstalk caused by the presence of the interaural canal, compound action potential (CAP) recordings were collected for two other adult barn owls. All BIC measurements were taken below the level of crosstalk. Results The ABR in barn owl showed 2-3 waves in the first 10 ms of recording. Wave I only appeared consistently at high levels. Wave II and III increased in amplitude and decreased in latency with increasing stimulus level. The most salient component of the BIC was a negative deflection (DN1) that corresponded to wave III. The latency of DN1 closely corresponded to the latency of local neurophonic potentials recorded in nucleus laminaris (Carr et al. 2015, J. Neurophysiol., in press). Both the amplitude and latency of DN1 varied with changing ITD. Conclusion The most visible component of the BIC (DN1) was associated with nucleus laminaris and is thus likely to reflect the known processes of ITD computation in this nucleus. DN1 was a negative deflection, which indicates a smaller response to binaural stimulation than predicted by the sum of monaural responses. This negative polarity is not consistent with previous predictions (Wada and Starr, 1989, Electroencephalogr. Clin. Neurophysiol. 56, 340–351) for an excitatory-excitatory system such as the one present in barn owl, and alternative models like the one by Gaumond and Psaltikidou (1991, J. Acoust. Soc. Am. 89: 454:456) need to be considered. Funding NPC, GL, CK funded by the DFG (TRR31) and the cluster of excellent “Hearing4all”. DK supported by the program “Function and pathophysiology of the auditory system” funded by the state of Lower Saxony, Germany.

Background Age-related hearing loss is well documented in gerbils more than 2 years old. Outer hair cell (OHC) loss, mostly used as an indicator of age-dependent hearing loss, is scattered and mainly found in apical and basal half-turns. However, loss of OHC is not well correlated with hearing loss, as assessed by CAP thresholds. In addition, inner hair cells (IHC) are rarely missing. A reduction in the number of synapses between afferent neurons and IHC has been reported in ageing mice (Sergeyenko, et al., J Neurosci., 2013, 33:13686-13694). In gerbils, few studies have focused on synapses, mainly due to technical difficulties with labeling (Meyer AC, et al. Nat Neurosci, 2009, 12:444-453). In this study, we present reliable pre- and postsynaptic immunoloabeling of afferent synapses in gerbils of different ages. We followed changes in the synapses with ageing, to investigate a potential mechanism for age-related hearing loss. Methods Quiet-aged gerbils, 2 to 43 months old, were perfused transcardially with 4% paraformaldehyde under deep anesthesia with sodium pentobarbital. Cochleae were harvested immediately after perfusion and decalcified in 0.5 M EGTA for 2 days at 4°C. An anti-CTBP2 antibody (BD Biosciences, No. 612044) and an anti-GluR2 (Millipore MAB 397) were used to label presynaptic ribbons and postsynaptic receptors, respectively. An anti-Myosin VIIa antibody (Proteus Biosciences 25-6790) labeled hair cells. Four different regions, located at 3.8, 5.19, 6.64, and 8.13 mm from the apex, corresponding to 2, 4, 8 and 16 kHz respectively (Müller M, Hear Res, 1996, 94:148–156) were examined with confocal microscopy. At each location, structures co-labeled with anti-CtBP2 and anti-GluA2 were defined as functional afferent synapses and quantified. Results The staining methods for both pre- and post-synaptic markers were reliable and repeatable at all ages. The total length of 6 cochleae analyzed to date was 11.6 ±0.45 mm. Preliminary data showed that both the pre- and post- synaptic markers decreased with age. At the 2 kHz region, afferent synapse numbers changed from 21/IHC in gerbils between 2 and 17 months of age, to 10.6/IHC in 43 months old animals. At the regions corresponding to 4, 8, and 16 kHz, synapse numbers decreased more gradually with age. Discussion In conclusion, synapse loss occurs much earlier than OHC loss in ageing gerbils and therefore could be a more reliable indicator of age-related hearing loss. However, the relation between synapse loss and age-related hearing loss still needs clarification. Funding This research is supported by the program of Cluster of Excellence “Hear4all”.

Background Neurons in the mammalian lateral superior olive (LSO) detect interaural level differences by comparing excitatory inputs from the ipsilateral cochlear nucleus with inhibitory inputs driven by contralateral sounds. LSO neurons also show sensitivity to binaural phase-differences of amplitude-modulated (AM) sounds. Although binaural coding by LSO has been extensively studied both theoretically and experimentally, monaural response characteristics of LSO to AM sounds are only marginally understood. Previous in vivo recordings in cat LSO showed that spiking rates of LSO neurons generally decrease with increasing modulation frequency, but that variations of modulation-frequency dependence across neurons were considerably large (Joris and Yin, 1998, J. Neurophysiol.). In this study, we aim to reveal the underlying mechanisms for this monaural AM coding using a simple computational model of LSO. Methods Phase-locked excitatory inputs to LSO were modeled as an inhomogeneous Poisson process with a periodic intensity function, while spontaneous inhibition was modeled as homogeneous Poisson process. Similar to a previous modeling study (Franken et al., 2014, Front. Neural Circuits), the LSO neuron was modeled as a counter of coincident inputs. Namely, if the number of excitatory inputs within a preset coincidence window reached or exceeded the threshold, an output spike was generated. Then the model is in the refractory period, in which no more spikes are generated. Effects of inhibition were modeled as a transient increase in threshold. We systematically varied parameters of the model and examined how they affect AM-tuning of the model neuron. Results By changing the model parameters, most variations of AMtuning curves observed in vivo were reproduced. Frequencydependence of input parameters (spike rates, degrees of phase-locking, and spontaneous inhibition) had only minor effects on LSO output spike rates. In contrast, increasing coincidence threshold or shortening the coincidence window resulted in lower output spike rates. Moreover, lower coincidence thresholds led to higher half-peak positions of AM-tuning curves. The duration of the refractory period affected the AM-tuning curve only below 300 Hz. Conclusion Our modeling results suggest that coincidence detection is one of the most fundamental operations in LSO and that variations of coincidence parameters may explain the empirical neuronto- neuron variations in AM coding. Investigating the relations between the abstract parameters of our coincidence counting model and underlying biophysical factors (such as membrane and synaptic properties) would be an important subject of future study. Funding Supported by the Cluster of Excellence “Hearing4all” (GA, JK), by the NIH Grant DC011555 (DJT), and by a Hanse-Wissenschaftskolleg (HWK) Fellowship (DJT).

The cell body of the outer hair cells connects the reticular lamina and the basilar membrane through supporting cells. According to the predominant view of cochlear mechanics, the outer hair cells enhance wave propagation in the scala media by dynamically expanding and contracting their body, thus providing an active driving force to the basilar membrane. In order to maximize the efficiency of such mechanism, the reticular lamina should behave like a rigid anchor; in this way the force associated with the length change of the outer hair cells body is efficiently transmitted to the basilar membrane. On the other hand, the motion of the reticular lamina provides a direct drive to the inner-hair cells through a fluid-cilia coupling mechanism. Therefore a free-to-move reticular lamina would be highly responsive to the activity of outer hair cells, thus locally enhancing the sensitivity of inner hair cells. Within this view, the reticular lamina should trade-off between the two conflicting requirements of 1) providing a firm attachment to the outer hair cells and 2) being sensitive to outer hair cells motility. A different thesis, partially supported by recent recordings of the intact organ of Corti, is that a longitudinal coupling of motion in the scala media (similar as in feed-forward cochlear models) allows for a simultaneous enhancement of basilar membrane and stereocilia vibrations without imposing contradicting requirements for the functioning of the reticular lamina. In this study, we discuss the recent experimental and theoretical findings under this perspective.

Classical recordings from the basal region of the chinchilla cochlea (~8 kHz) show that neural tuning curves lie about halfway between basilar-membrane (BM) constant-velocity and constant-displacement tuning curves. This suggests that inner-hair cells (IHCs) respond to a combination of BM velocity and displacement; a statement that finds support in classical guinea-pig IHC recordings. In this study, we offer an explanation for the well-documented relationship between neural and mechanical tuning that relies on a proportionality between IHCs stereocilia deflection amplitude and BM velocity up to the units’ best frequency. By assuming well-established features of IHC processing, i.e. a Boltzmann type transduction nonlinearity followed by the low-pass filtering action of the IHC basolateral membrane, we derive the theoretical background for this work. We then validate our hypothesis using numerical simulations in a computational model of the inner hair cell/auditory nerve complex. Unfortunately, the demonstrated proportionality between BM velocity and stereocilia deflection seems in contrast with recent in-vivo recordings from the ~18 kHz region of the guinea-pig cochlea that show a level-dependent sharper tuning of the reticular lamina (RL) compared to BM tuning. To resolve this discrepancy, we propose the existence of a mode of RL vibration that reflects the motion of the BM in a more basal cochlear region at a fixed distance. This mode of vibration can account for sharper RL than BM tuning in the 18 kHz region through a phase cancellation mechanism and we show this numerically using a linear nonlocal model that relates RL and BM vibrations. The suggested phase cancellation mechanism results in a mode that enhances RL vibrations at high-frequencies (above 10 kHz), but that leaves lower-frequency responses unaffected in agreement with the differences observed in the high (~18 kHz; guinea pig) vs lower (~8 kHz; chinchilla) frequency cochlear mechanics. Additionally, the proposed linear model is capable of capturing the apparent nonlinear relationship between RL and BM motion. We propose a description of BM-RL-IHC transduction that is based on previous BM and IHC models, combined with (i) frequency dependent stereocilia low-pass filtering and (ii) a feedforward model of RL motion, and demonstrate that it can account for well-documented relationships between mechanical and neural tuning. We lastly point out that established functional models of the IHC/auditory-nerve complex tend to overestimate the neural response to lowfrequency stimuli, resulting from an excessive low-pass filtering in the IHC stage. Funding Work supported by Aalto ELEC doctoral school and DFG Cluster of Excellence EXC 1077/1 "Hearing4all".

and aging can reduce the number and types of auditorynerve fibers responsible for a robust coding of sound to the auditory brainstem. Even though a temporal coding deficit associated with auditory-nerve and brainstem processing has been linked to degraded amplitude-modulation detection in listeners with normal audiometric thresholds, it is not clear how these supra-threshold hearing deficits interact with the outer-hair-cell-loss component of hearing loss. As listeners with elevated audiometric thresholds likely suffer from a mixture of peripheral pathologies, it is important to understand which of the hearing deficits is perceptually more dominant in specific listening conditions. The present study separated cochlear mechanical hearing deficits derived from DPOAE growth functions from brainstem coding fidelity measures (ABR and EFR) in listeners with normal and mildly-sloping audiograms, and compared these metrics to psychoacoustic amplitude-modulation (AM) detection performance. Specifically, we adopted a differential paradigm in which we tested how badly various types of masking noises impact AM detection performance. The fixedlevel wideband noise masker condition was designed to inform about how auditory filter widening and coding fidelity impact AM detection performance. In the second, narrowband masker (40Hz), condition, we expected performance to be limited by temporal coding fidelity within a single auditory filter. AM detection thresholds to 65 and 70 dB SPL, 100-Hzmodulated 4-kHz pure tones were measured in 18 listeners in the quiet and two masker conditions. Two stimulus configurations were considered for the elevated-threshold group: in the first, stimulus levels were adjusted according to equal sensation level (SL); in the second, stimulus levels were kept constant. AM detection performance in quiet was similar for both the elevated-threshold and normal-threshold group when stimuli were presented at equal SL. For that same condition, AM thresholds were significantly more robust against the broadband noise in the elevated-threshold group. However, for the fixed level condition, AM detection was significantly worse in the elevated-threshold group and the broadband noise degraded AM detection more in the normal-hearing group. The narrowband masker impacted both groups similarly in the equal SL condition, but had nearly no effect on the elevated-threshold group when stimuli were presented at fixed levels. We are currently further relating the psychoacoustic results to the recorded physiological metrics to elucidate which subcomponents of peripheral hearing loss are responsible for AM detection performance in the different masker conditions. Funding DFG Cluster of Excellence EXC 1077/1 "Hearing4all"

In many situations the meaning of a stimulus is the same despite fluctuations in its overall strength. A visual scene’s content does not depend on light intensity, or a word utterance should be recognised irrespective of its loudness. Nonetheless, gain fluctuations are an integral part of the input statistics and they can help differentiate between stimuli. In the visual domain, for instance objects of the same class are likely to have similar surface properties, resulting in a distinct distribution of light intensities. Light intensities can therefore help identify objects. The neural underpinnings of such computation are unclear. Existing models discard gain information by ad hoc preprocessing (Nessler, 2009; Keck, 2012) or by divisive normalisation (Schwarz, 2001) before learning the input statistics from normalized data. Overall, it is unknown how neural circuits can robustly extract statistical regularities in their inputs when the overall intensity of stimuli is variable. Here we develop a principled account of unsupervised learning in the face of gain variations. We introduce a novel generative mixture model (Product- Poisson-Gamma) that explicitly models the statistics of stimulus intensity, and we derive a biologically-plausible neural circuit implementation for inference and learning in this model. We find that explicitly taking into account gain variations improves the robustness of unsupervised learning, as differences in input strength help distinguish between classes with similar features but different gain statistics. From a biological perspective, the derived neural circuit, in which feature-sensitive neurons are equipped with a specific form of intrinsic plasticity (IP), provides novel insights into the interaction between Hebbian and IP during learning. Furthermore, our results imply that neural excitability reflects nontrivial input statistics, in particular the intensity of the features to which a neuron is sensitive.

Overview The present study focuses on the identification of morphological differences of Cav1.3 knock-out mice in comparison to wild type mice by application of different methods. Cav1.3 knock-out mice lack the voltage-gated L-type Ca2+ channels Cav1.3. This channel controls vesicle fusion and subsequent neurotransmitter release from cochlear inner hair cells to afferent auditory nerve fibers. Cav1.3 knock-out mice display a developmental failure of cochlear structures. This study aimed at the characterization of early and late stage of the degenerative process in the inner ear in order to identify suitable time-point for therapeutic interventions concerning preservation of hair cell function and regeneration of the auditory nerve. Methods Wild type mice and knock-out mice were used for the isolation of the cochleae and fixed by immersion of PFA (4%). For immunocytochemistry, the cochleae were dissected into basal, medial and apical sections and these were stained with CtBP2, Otoferlin and DAPI for counting the number of synaptic ribbons per inner hair cell. For scanning laser optical tomography (SLOT), decalcification, dehydration, optical clearing and antibody staining of the whole cochlea were performed. For visualization of myelinated nerve fibers, the cochleae were stained with osmium. Results Coupling of SLOT and immunocytochemistry allowed the overview of whole cochleae to show specific anatomical structures and selective mapping of cellular structures (hair cells and afferent nerve fibers respectively). Accordingly, the number of synaptic ribbons in the Cav1.3 knock-out mice is decreased along the different cochlear turns compared to wild type mice as shown previously. The decrease starts around postnatal day (P) 9 in the basal and medial turn of the cochlea and around P20 in the apical turn. A slightly reduced myelination and density of afferent auditory fibers was shown by osmium staining of the cochlea at P18 Conclusions This study reveals that SLOT is a suitable tool in the field of otology for in toto visualization of the internal structure of the cochlea. By means of the different methods, we showed that the degenerative processes start as early as P9 in the basal and medial turn of the cochleae of Cav1.3 knock-out mice and proceed to the apical turn at about P20. Funding Cluster of Excellence “Hearing4all”

Rod outer segment guanylate cyclase 1 (ROS-GC1) is a pivotal enzyme for vertebrate phototransduction and the systematically growing evidence point to its connection with processes other than phototransduction within and outside the retina. ROS-GC1 activity is regulated by Ca2+ in two opposite modes. This regulation is indirect and occurs through Ca2+-binding proteins. At nanomolar Ca2+ concentrations, ROS-GC1 is activated by GCAPs and at micromolar Ca2+-concentrations, by S100β and neurocalcin. The former mode operates in phototransduction and the latter was proposed to play a role in synaptic activity. The last possibility was supported by findings of ROS-GC1 expression not only in various retinal layers other than photoreceptor outer segments but also outside the retina, in pineal gland and olfactory bulb. If ROS-GC1 indeed is to play a role in neurotransmission its expression must be colocalized with its Ca2+-dependent regulators and with possible targets of an increased cyclic GMP concentration, cyclic nucleotide-gated channels or cyclic GMP-dependent protein kinase, in synaptic regions. In this review these aspects of ROS-GC1 expression in retina, pineal gland and olfactory bulb are discussed.

The notion of predictive coding is a common feature of many theories of auditory information processing. Experimental demonstrations of predictive auditory processing often rest on omitting predictable input in order to uncover the prediction made by the brain. Findings show that auditory cortical activity elicited by the omission of a predictable tone resembles the activity elicited by the actual tone. Here we attempted to extend this approach towards using noises instead of omissions in order to capture a more prevalent case of degraded sensory input. By applying a subtraction approach to remove ERP effects of the noise itself, auditory cortical activity elicited "behind" the noise was uncovered. We hypothesized that ERPs elicited behind noise stimuli covering predictable tones should be more similar to ERPs elicited by the actual tones than when the same comparison is made for unpredictable tones. ERP results during passive listening partly confirm this hypothesis, but also point towards some methodological caveats in this particular approach towards studying neural correlates of predictive auditory processing due to contributions from predictability-unrelated factors. A follow-up active listening condition indicated that participants were not more likely to perceive the tone sequence as continuous when a predictable tone was covered with noise than when this pertained to an unpredictable tone. Overall, the noise-based paradigm in its present form was not shown to be successful in revealing predictive processing in perceptual judgments or early neural correlates of sound processing. We discuss these findings in the contexts of predictive processing and illusory auditory continuity. This article is part of a Special Issue entitled SI: Prediction and Attention

The dynamic attending theory as originally proposed by Jones, 1976. Psychol. Rev. 83(5), 323-355 posits that tone sequences presented at a regular rhythm entrain attentional oscillations and thereby facilitate the processing of sounds presented in phase with this rhythm. The increased interest in neural correlates of dynamic attending requires robust behavioral indicators of the phenomenon. Here we aimed to replicate and complement the most prominent experimental implementation of dynamic attending (Jones et al., 2002. Psychol. Sci. 13(4), 313-319). The paradigm uses a pitch comparison task in which two tones, the initial and the last of a longer series, have to be compared. In-between the two, distractor tones with variable pitch are presented, at a regular pace. A comparison tone presented in phase with the entrained rhythm is hypothesized to lead to better behavioral performance. Aiming for a conceptual replication, four different variations of the original paradigm were created which were followed by an exact replication attempt. Across all five experiments, only 40 of the 140 tested participants showed the hypothesized pattern of an inverted U-shaped profile in task accuracy, and the group average effects did not replicate the pattern reported by Jones et al., 2002. Psychol. Sci. 13(4), 313-319 in any of the five experiments. However, clear evidence for a relationship between musicality and overall behavioral performance was found. This study casts doubt on the suitability of the pitch comparison task for demonstrating auditory dynamic attending. We discuss alternative tasks that have been shown to support dynamic attending theory, thus lending themselves more readily to studying its neural correlates. This article is part of a Special Issue entitled SI: Prediction and Attention

Separating concurrent sounds is fundamental for a veridical perception of one's auditory surroundings. Sound components that are harmonically related and start at the same time are usually grouped into a common perceptual object, whereas components that are not in harmonic relation or have different onset times are more likely to be perceived in terms of separate objects. Here we tested whether neonates are able to pick up the cues supporting this sound organization principle. We presented newborn infants with a series of complex tones with their harmonics in tune (creating the percept of a unitary sound object) and with manipulated variants, which gave the impression of two concurrently active sound sources. The manipulated variant had either one mistuned partial (single-cue condition) or the onset of this mistuned partial was also delayed (double-cue condition). Tuned and manipulated sounds were presented in random order with equal probabilities. Recording the neonates' electroencephalographic responses allowed us to evaluate their processing of the sounds. Results show that, in both conditions, mistuned sounds elicited a negative displacement of the event-related potential (ERP) relative to tuned sounds from 360 to 400 ms after sound onset. The mistuning-related ERP component resembles the object-related negativity (ORN) component in adults, which is associated with concurrent sound segregation. Delayed onset additionally led to a negative displacement from 160 to 200 ms, which was probably more related to the physical parameters of the sounds than to their perceptual segregation. The elicitation of an ORN-like response in newborn infants suggests that neonates possess the basic capabilities of segregating concurrent sounds by detecting inharmonic relations between the co-occurring sounds

The main objective of this study was to investigate the extent to which hearing impairment influences the duration of sentence processing. An eye-tracking paradigm is introduced that provides an online measure of how hearing impairment prolongs processing of linguistically complex sentences; this measure uses eye fixations recorded while the participant listens to a sentence. Eye fixations toward a target picture (which matches the aurally presented sentence) were measured in the presence of a competitor picture. Based on the recorded eye fixations, the single target detection amplitude, which reflects the tendency of the participant to fixate the target picture, was used as a metric to estimate the duration of sentence processing. The single target detection amplitude was calculated for sentence structures with different levels of linguistic complexity and for different listening conditions: in quiet and in two different noise conditions. Participants with hearing impairment spent more time processing sentences, even at high levels of speech intelligibility. In addition, the relationship between the proposed online measure and listener-specific factors, such as hearing aid use and cognitive abilities, was investigated. Longer processing durations were measured for participants with hearing impairment who were not accustomed to using a hearing aid. Moreover, significant correlations were found between sentence processing duration and individual cognitive abilities (such as working memory capacity or susceptibility to interference). These findings are discussed with respect to audiological applications

This study presents first evidence that reliable EEG data can be recorded with a new cEEGrid electrode array, which consists of ten electrodes printed on flexible sheet and arranged in a c-shape to fit around the ear. Ten participants wore two cEEGrid systems for at least seven hours. Using a smartphone for stimulus delivery and signal acquisition, resting EEG and auditory oddball data were collected in the morning and in the afternoon six to seven hours apart. Analysis of resting EEG data confirmed well-known spectral differences between eyes open and eyes closed conditions. The ERP results confirmed the predicted condition effects with significantly larger P300 amplitudes for target compared to standard tones, and a high test-retest reliability of the P300 amplitude (r > = .74). Moreover, a linear classifier trained on data from the morning session revealed similar performance in classification accuracy for the morning and the afternoon sessions (both > 70%). These findings demonstrate the feasibility of concealed and comfortable brain activity acquisition over many hours

During the transmission of acoustic signals, the spectral and temporal properties of the original signal are degraded, and with increasing distance more and more echo patterns are imposed. It is well known that these physical alterations provide useful cues to assess the distance of a sound source. Previous studies in birds have shown that birds employ the degree of degradation of a signal to estimate the distance of another singing male (referred to as ranging). Little is known about how acoustic masking by background noise interferes with ranging, and if the number of song elements and stimulus familiarity affect the ability to discriminate between degraded and undegraded signals. In this study we trained great tits (Parus major L.) to discriminate between signal variants in two background types, a silent condition and a condition consisting of a natural dawn chorus. We manipulated great tit song types to simulate patterns of reverberation and degradation equivalent to transmission distances of between 5 and 160 m. The birds' responses were significantly affected by the differences between the signal variants and by background type. In contrast, stimulus familiarity or their element number had no significant effect on signal discrimination. Although background type was a significant main effect with respect to the response latencies, the great tits' overall performance in the noisy dawn chorus was similar to the performance in silence

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case-control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings

α-Synuclein (α-syn) positive glial cytoplasmic inclusions (GCI) originating in oligodendrocytes (ODC) are a characteristic hallmark in multiple system atrophy (MSA). Their occurrence may be linked to a failure of the ubiquitin proteasome system (UPS) or the autophagic pathway. For proteasomal degradation, proteins need to be covalently modified by ubiquitin, and deubiquitinated by deubiquitinating enzymes (DUBs) before proteolytic degradation is performed. The DUB ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a component of the UPS, it is abundantly expressed in neuronal brain cells and has been connected to Parkinson's disease (PD). It interacts with α-syn and tubulin. The present study was undertaken to investigate whether UCH-L1 is a constituent of ODC, the myelin forming cells of the CNS, and is associated with GCIs in MSA. Furthermore, LDN-57444 (LDN), a specific UCH-L1 inhibitor, was used to analyze its effects on cell morphology, microtubule (MT) organization and the proteolytic degradation system. Towards this an oligodendroglial cell line (OLN cells), stably transfected with α-syn or with α-syn and GFP-LC3, to monitor the autophagic flux, was used. The data show that UCH-L1 is expressed in ODC derived from the brains of newborn rats and colocalizes with α-syn in GCIs of MSA brain sections. LDN treatment had a direct impact on the MT network by affecting tubulin posttranslational modifications, i.e., acetylation and tyrosination. An increase in α-tubulin detyrosination was observed and detyrosinated MT were abundantly recruited to the cellular extensions. Furthermore, small α-syn aggregates, which are constitutively expressed in OLN cells overexpressing α-syn, were abolished, and LDN caused the upregulation of the autophagic pathway. Our data add to the knowledge that the UPS and the autophagy-lysosomal pathway are tightly balanced, and that UCH-L1 and its regulation may play a role in neurodegenerative diseases with oligodendroglia pathology

Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs process outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination process