Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation.

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDC). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HC) and bilaterally congenitally deaf cats (CDC). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing the predominant effect of each ear is excitation of auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.Significance statement Congenital single-sided deafness is a clinically relevant form of hearing loss. We studied this phenomenon in a unique animal model with congenital deafness of one ear and normal hearing of the other ear with electrical stimulation on both ears. Differential effects of single-sided deafness on interaural time and level difference sensitivity were observed, consistent with the aural preference syndrome. The influence of the previously hearing ear became dominant and the deaf ear mildly suppressive in the majority of units in both hemispheres, resulting in an inconsistent representation of binaural cues. These changes in neuronal representation of the two ears explain why late restoration with cochlear implants in single-sided deafness often results in insufficient benefit of the previously deaf ear.

Theta and alpha oscillatory signatures of auditory sensory and cognitive loads during complex listening.

The neuronal signatures of sensory and cognitive load provide access to brain activities related to complex listening situations. Sensory and cognitive loads are typically reflected in measures like response time (RT) and event-related potentials (ERPs) components. It's, however, strenuous to distinguish the underlying brain processes solely from these measures. In this study, along with RT- and ERP-analysis, we performed time-frequency analysis and source localization of oscillatory activity in participants performing two different auditory tasks with varying degrees of complexity and related them to sensory and cognitive load. We studied neuronal oscillatory activity in both periods before the behavioral response (pre-response) and after it (post-response). Robust oscillatory activities were found in both periods and were differentially affected by sensory and cognitive load. Oscillatory activity under sensory load was characterized by decrease in pre-response (early) theta activity and increased alpha activity. Oscillatory activity under cognitive load was characterized by increased theta activity, mainly in post-response (late) time. Furthermore, source localization revealed specific brain regions responsible for processing these loads, such as temporal and frontal lobe, cingulate cortex and precuneus. The results provide evidence that in complex listening situations, the brain processes sensory and cognitive loads differently. These neural processes have specific oscillatory signatures and are long lasting, extending beyond the behavioral response.

[Surgical Treatment of Tuberculous Spondylodiscitis]. / Operacní lécba tuberkulózní spondylodiscitidy.

PURPOSE OF THE STUDY The paper presents a monocentric retrospective study of patients treated surgically for spinal tuberculosis. Clinical and radiological results are analysed, early and late complications are recorded. The study aims to answer the following questions. 1. Can we use instrumentation to restore the stability and alignment in the infected spinal focus? 2. Should we always perform radical anterior resection of TBC lesions? 3. What is the prognosis of surgical treatment of TBC patients with neurological deficit manifestation? MATERIAL AND METHODS Between 2010 and 2020, a total of 12 patients were treated for spinal tuberculosis at our department, of whom 9 patients (5 men, 4 women) with the mean age of 47.3 years (range 29 to 83 years) underwent a surgery. A total of three patients were operated on before the final confirmation of the TBC and treatment with antituberculosis medication, four patients in the initial therapy phase and two patients in the continuous phase. Two patients only underwent a non-instrumented decompression surgery followed by external support fixation. In the other seven patients, always with spinal deformity, instrumentation was used (3 cases of isolated posterior decompression, transpedicular fixation, posterior fusion, 4 cases of anteroposterior instrumented reconstruction). In 2 cases a structural bone graft and in 2 cases an expandable titanium cage were used for anterior column reconstruction. RESULTS Of the total number of patients, altogether eight patients were assessed at 1 year after surgery (one 83-year-old patient died from heart failure 4 months after surgery). Of the remaining eight patients, three patients exhibited a neurological deficit and postoperative regression of the finding. The McCormick score improved from the preoperative mean score of 3.25 to 1.62 at 1 year after surgery (p < 0.001). The clinical VAS score regressed from 5.75 to 1.63 at 1 year after surgery (p < 0.001). Radiographic healing of the anterior fusion was achieved in all patients, both after decompression and instrumented surgery. The initial mean kyphosis of 20.36 degrees of the operated segment measured by the mCobb angle was corrected to 14.6 degrees postoperatively, with a subsequent slight deterioration to 14.86 degrees (p < 0.05). The greatest correction was achieved in patients who had undergone a two-stage surgery with anterior resection and AP reconstruction. DISCUSSION In our cohort, titanium instrumentation was used in seven of nine patients. One patient only manifested persistent tuberculosis with nonspecific bacterial flora superinfection. Revision surgery with anterior radical debridement and subsequent treatment with antituberculotic drugs healed the patient. There were four patients with major preoperative neurological deficit persisting more than 2 weeks before the final treatment with subsequent improvement in all cases. These patients were treated with anteroposterior reconstruction and anterior radical debridement. CONCLUSIONS No increased risk of recurrent infection associated with the use of spinal instrumentation was found in the study. Anterior radical debridement is performed in patients with manifested kyphotic deformity and spinal canal compression, followed by reconstruction with a structural bone graft or a titanium cage. The other patients are treated based on the principle of "optimal" debridement with or without the use of transpedicular instrumentation. If adequate spinal canal decompression and stability are achieved, neurological improvement can be anticipated even in case of a major neurological deficit. Key words: spine tuberculosis, tuberculous spondylitis, Pott's disease, anterior debridement, spine instrumentation.

Publisher Correction: Spiral Form of the Human Cochlea Results from Spatial Constraints.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

New thin-film surface electrode array enables brain mapping with high spatial acuity in rodents.

In neuroscience, single-shank penetrating multi-electrode arrays are standard for sequentially sampling several cortical sites with high spatial and temporal resolution, with the disadvantage of neuronal damage. Non-penetrating surface grids used in electrocorticography (ECoG) permit simultaneous recording of multiple cortical sites, with limited spatial resolution, due to distance to neuronal tissue, large contact size and high impedances. Here we compared new thin-film parylene C ECoG grids, covering the guinea pig primary auditory cortex, with simultaneous recordings from penetrating electrode array (PEAs), inserted through openings in the grid material. ECoG grid local field potentials (LFP) showed higher response thresholds and amplitudes compared to PEAs. They enabled, however, fast and reliable tonotopic mapping of the auditory cortex (place-frequency slope: 0.7 mm/octave), with tuning widths similar to PEAs. The ECoG signal correlated best with supragranular layers, exponentially decreasing with cortical depth. The grids also enabled recording of multi-unit activity (MUA), yielding several advantages over LFP recordings, including sharper frequency tunings. ECoG first spike latency showed highest similarity to superficial PEA contacts and MUA traces maximally correlated with PEA recordings from the granular layer. These results confirm high quality of the ECoG grid recordings and the possibility to collect LFP and MUA simultaneously.

Spiral Form of the Human Cochlea Results from Spatial Constraints.

The human inner ear has an intricate spiral shape often compared to shells of mollusks, particularly to the nautilus shell. It has inspired many functional hearing theories. The reasons for this complex geometry remain unresolved. We digitized 138 human cochleae at microscopic resolution and observed an astonishing interindividual variability in the shape. A 3D analytical cochlear model was developed that fits the analyzed data with high precision. The cochlear geometry neither matched a proposed function, namely sound focusing similar to a whispering gallery, nor did it have the form of a nautilus. Instead, the innate cochlear blueprint and its actual ontogenetic variants were determined by spatial constraints and resulted from an efficient packing of the cochlear duct within the petrous bone. The analytical model predicts well the individual 3D cochlear geometry from few clinical measures and represents a clinical tool for an individualized approach to neurosensory restoration with cochlear implants.

Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea.

Profound hearing impairment can be overcome by electrical stimulation (ES) of spiral ganglion neurons (SGNs) via a cochlear implant (CI). Thus, SGN survival is critical for CI efficacy. Application of glial cell line-derived neurotrophic factor (GDNF) has been shown to reduce SGN degeneration following deafness. We tested a novel method for local, continuous GDNF-delivery in combination with ES via a CI. The encapsulated cell (EC) device contained a human ARPE-19 cell-line, genetically engineered for secretion of GDNF. In vitro, GDNF delivery was stable during ES delivered via a CI. In the chronic in vivo part, cats were systemically deafened and unilaterally implanted into the scala tympani with a CI and an EC device, which they wore for six months. The implantation of control devices (same cell-line not producing GDNF) had no negative effect on SGN survival. GDNF application without ES led to an unexpected reduction in SGN survival, however, the combination of GDNF with initial, short-term ES resulted in a significant protection of SGNs. A tight fibrous tissue formation in the scala tympani of the GDNF-only group is thought to be responsible for the increased SGN degeneration, due to mechanisms related to an aggravated foreign body response. Furthermore, the fibrotic encapsulation of the EC device led to cell death or cessation of GDNF release within the EC device during the six months in vivo. In both in vitro and in vivo, fibrosis was reduced by CI stimulation, enabling the neuroprotective effect of the combined treatment. Thus, fibrous tissue growth limits treatment possibilities with an EC device. For a stable and successful long-term neurotrophic treatment of the SGN via EC devices in human CI users, it would be necessary to make changes in the treatment approach (provision of anti-inflammatories), the EC device surface (reduced cell adhesion) and the ES (initiation prior to fibrosis formation).

[Pathophysiology of hearing loss : Classification and treatment options]. / Pathophysiologie des Hörverlusts : Klassifikation und Therapieoptionen.

From the therapeutic perspective, the etiology and pathophysiology of hearing loss can be classified based on the extent of the primary cause. Hearing loss can have very different consequences for cell preservation in the organ of Corti and the spiral ganglion. These not only have implications for prosthetic therapy outcome, but may also influence the potential for future causal molecular therapies. Etiologies leading to deficits that are limited to one or a few molecules without having an effect on cell survival have the greatest potential for future causal therapy using molecular and cellular approaches. Preliminary success for molecular therapy was recently reported in animal experiments. Unfortunately, the incidence of these types of hearing loss is very low and in the future the therapy of hearing loss will therefore also require several different approaches. In addition to peripheral pathophysiology, hearing loss has consequences on the functioning of the brain, which can vary greatly due to individual adaptation to the situation without hearing. The authors therefore argue for individualization of the diagnostics and therapy that focus not only the symptom of hearing loss, but also the individual pathophysiology and consequences. Only with individualized therapy can the success of treating hearing disorders be significantly improved.

Optoacoustic effect is responsible for laser-induced cochlear responses.

Optical stimulation of the cochlea with laser light has been suggested as an alternative to conventional treatment of sensorineural hearing loss with cochlear implants. The underlying mechanisms are controversially discussed: The stimulation can either be based on a direct excitation of neurons, or it is a result of an optoacoustic pressure wave acting on the basilar membrane. Animal studies comparing the intra-cochlear optical stimulation of hearing and deafened guinea pigs have indicated that the stimulation requires intact hair cells. Therefore, optoacoustic stimulation seems to be the underlying mechanism. The present study investigates optoacoustic characteristics using pulsed laser stimulation for in vivo experiments on hearing guinea pigs and pressure measurements in water. As a result, in vivo as well as pressure measurements showed corresponding signal shapes. The amplitude of the signal for both measurements depended on the absorption coefficient and on the maximum of the first time-derivative of laser pulse power (velocity of heat deposition). In conclusion, the pressure measurements directly demonstrated that laser light generates acoustic waves, with amplitudes suitable for stimulating the (partially) intact cochlea. These findings corroborate optoacoustic as the basic mechanism of optical intra-cochlear stimulation.

Extended boiling of peanut progressively reduces IgE allergenicity while retaining T cell reactivity.

BACKGROUND: Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. OBJECTIVE: To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. METHODS: Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS-PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/CD25+/CD134+ T cells in peanut-allergic and non-allergic individuals. RESULTS: Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. CONCLUSION AND CLINICAL RELEVANCE: Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy.

Cystatin C Is Associated with the Extent and Characteristics of Coronary Atherosclerosis in Patients with Preserved Renal Function.

Cystatin C (CysC), an endogenous inhibitor of cysteine proteases and a sensitive and accurate marker of renal function, is associated with the severity of coronary atherosclerosis assessed by angiography and future cardiovascular events according to previous studies. We aimed to evaluate the association between CysC levels and coronary plaque volume, composition and phenotype assessed by intravascular ultrasound and intravascular ultrasound-derived virtual histology in patients with preserved renal function. Forty-four patients with angiographically documented coronary artery disease and complete intravascular imaging were included in the study. Patients were categorized into tertiles by CysC levels. Subjects in the high CysC tertile had significantly higher mean plaque burden (48.0 % ± 6.9 vs. 42.8 % ± 7.4, P = 0.029), lower mean lumen area (8.1 mm2 ± 1.7 vs. 9.9 mm2 ± 3.1, P = 0.044) and a higher number of 5-mm vessel segments with minimum lumen area < 4 mm2 (17.9 ± 18.9 vs. 6.8 ± 11.7, P = 0.021) compared to patients in the lower tertiles. In addition, CysC levels demonstrated significant positive correlation with the mean plaque burden (r = 0.35, P = 0.021). Neither relative, nor absolute plaque components differed significantly according to CysC tertiles. The Liverpool Active Plaque Score was significantly higher in the high CysC tertile patients (0.91 ± 1.0 vs. 0.18 ± 0.92, P = 0.02). In conclusion, our study demonstrated a significant association of increased CysC levels with more advanced coronary artery disease and higher risk plaque phenotype in patients with preserved renal function.

Replication of ZNF804A gene variant associations with risk of heroin addiction.

Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex. In this independent replication study, we tested the rs7597593 and rs1344706 SNP genotypes and their corresponding haplotypes for association with heroin addiction using cases drawn from the Urban Health Study and population controls: total N = 10 757 [7095 European Americans (EAs) and 3662 African Americans (AAs)]. We independently replicated both ZNF804A SNP associations in EAs: the rs7597593-T (P = 0.016) and rs1344706-A (P = 0.029) alleles both being associated with increased risk of heroin addiction, consistent with the prior report. Neither SNP was associated in AAs alone, but meta-analysis across both ancestry groups resulted in significant associations for rs1344706-A [P = 0.016, odds ratio (95% confidence interval) = 1.13 (1.02-1.25)] and its haplotype with rs7597593-T [P = 0.0067, odds ratio (95% confidence interval) = 1.16 (1.04-1.29)]. By showing consistent associations across independent studies and diverse ancestry groups, our study provides evidence that these two ZNF804A SNPs and their risk haplotype are among the few replicable genetic associations with heroin addiction.

Electric-acoustic interactions in the hearing cochlea: single fiber recordings.

The present study investigates interactions of simultaneous electric and acoustic stimulation in single auditory nerve fibers in normal hearing cats. First, the auditory nerve was accessed with a microelectrode and response areas of single nerve fibers were determined for acoustic stimulation. Second, response thresholds to extracochlear sinusoidal electric stimulation using ball electrodes positioned at the round window were measured. Third, interactions that occurred with combined electric-acoustic stimulation were investigated in two areas: (1) the spectral domain (frequency response areas) and (2) the temporal domain (phase-locking to each stimulus) at moderate stimulus intensities (electric: 6 dB re threshold, acoustic: 20-40 dB re threshold at the characteristic frequency, CF). For fibers responding to both modalities responses to both electric and acoustic stimulation could be clearly identified. CFs, thresholds, and bandwidth (Q10dB) of acoustic responses were not significantly affected by simultaneous electric stimulation. Phase-locking of electric responses decreased in the presence of acoustic stimulation. Indication for electric stimulation of inner hair cells with 125 and 250 Hz were observed. However, these did not disturb the acoustic receptive fields of auditory nerve fibers. There was a trade-off between these responses when the intensities of the stimulation were varied: Relatively more intense stimulation dominated less intense stimulation. The scarcity of interaction between the different stimulus modalities demonstrates the ability of electric-acoustic stimulation to transfer useful information through both stimulation channels at the same time despite cochlear electrophonic effects. Application of 30 Hz electric stimulation resulted in a strong suppression of acoustic activity in the anodic phase of the stimulus. An electric stimulation like this might thus be used to control acoustic responses. This article is part of a Special Issue entitled .

Response properties of local field potentials and multiunit activity in the mouse visual cortex.

Extracellular local field potentials (LFPs) and multiunit activity (MUA) reflect the spatially integrated activity of multiple neurons in a given cortical structure. In the cat and primate visual cortices, these signals exhibit selectivity for visual stimulus features, such as orientation, direction of motion or spatial frequency. In the mouse visual cortex, a model which has been increasingly used in visual neuroscience, the visual stimulus selectivity of population signals has not been examined in detail. We recorded LFPs and MUA using multielectrode arrays and two derived measures, the high-pass filtered continuous MUA and the bipolar first spatial derivative of the LFP, in the visual cortex of isoflurane-anesthetized C57Bl/6 mice. We analyzed the onset latency and characterized the receptive fields in addition to the direction, orientation, and spatial and temporal frequency preferences of these signals. Population signals exhibited onset latencies as short as ∼30ms and possessed receptive fields as large as ∼38° with MUA receptive fields smaller than those of LFPs. All four population signals exhibited similar spatial frequency preferences (∼0.1 cycles per degree) and temporal frequency preferences (∼1 cycle per second). However, for all population signals, spatial and frequency tunings were broad and orientation and direction of motion preferences were absent. The characterization of the visual stimulus selectivity of LFPs and MUA in the mouse visual cortex should provide information regarding their usability in characterizing stimulus properties and disclose possible limitations.

Prediction of coronary vessel involvement on the basis of atherosclerosis risk factor analysis.

The prediction of coronary vessel involvement by means of noninvasive tests is one of the fundamental objectives of preventive cardiology. This review describes the current possibilities of coronary vessel involvement prediction by means of ultrasonographic examination of carotid arteries, analysis of polymorphisms in the genes encoding enzymes responsible for production of nitric oxide and carbon monoxide and assessment of levels of certain proinflammatory cytokines. In the presented work these noninvasive markers are correlated with the extent of coronary vessel involvement as assessed by coronary angiography, intravascular ultrasound and virtual histology (Fig. 5, Ref. 40).

Auditory critical periods: a review from system's perspective.

The article reviews evidence for sensitive periods in the sensory systems and considers their neuronal mechanisms from the viewpoint of the system's neuroscience. It reviews the essential cortical developmental steps and shows its dependence on experience. It differentiates feature representation and object representation and their neuronal mechanisms. The most important developmental effect of experience is considered to be the transformation of a naive cortical neuronal network into a network capable of categorization, by that establishing auditory objects. The control mechanisms of juvenile and adult plasticity are further discussed. Total absence of hearing experience prevents the patterning of the naive auditory system with subsequent extensive consequences on the auditory function. Additional to developmental changes in synaptic plasticity, other brain functions like corticocortical interareal couplings are also influenced by deprivation. Experiments with deaf auditory systems reveal several integrative effects of deafness and their reversibility with experience. Additional to developmental molecular effects on synaptic plasticity, a combination of several integrative effects of deprivation on brain functions, including feature representation (affecting the starting point for learning), categorization function, top-down interactions and cross-modal reorganization close the sensitive periods and may contribute to their critical nature. Further, non-auditory effects of auditory deprivation are discussed. To reopen critical periods, removal of molecular breaks in synaptic plasticity and focused training therapy on the integrative effects are required.

Development of brainstem-evoked responses in congenital auditory deprivation.

To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs) and hearing controls (HCs) were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed. Electrically evoked auditory brainstem responses (E-ABRs) were recorded with monopolar stimulation at different current levels. CDCs demonstrated extensive development of E-ABRs, from first signs of responses at postnatal (p.n.) day 3 through appearance of all waves of brainstem response at day 8 p.n. to mature responses around day 90 p.n.. Wave I of E-ABRs could not be distinguished from the artifact in majority of CDCs, whereas in HCs, it was clearly separated from the stimulus artifact. Waves II, III, and IV demonstrated higher thresholds in CDCs, whereas this difference was not found for wave V. Amplitudes of wave III were significantly higher in HCs, whereas wave V amplitudes were significantly higher in CDCs. No differences in latencies were observed between the animal groups. These data demonstrate significant postnatal subcortical development in absence of hearing, and also divergent effects of deafness on early waves II-IV and wave V of the E-ABR.

Genetic variation screening of TNNT2 gene in a cohort of patients with hypertrophic and dilated cardiomyopathy.

Mutations in troponin T (TNNT2) gene represent the important part of currently identified disease-causing mutations in hypertrophic (HCM) and dilated (DCM) cardiomyopathy. The aim of this study was to analyze TNNT2 gene exons in patients with HCM and DCM diagnosis to improve diagnostic and genetic consultancy in affected families. All 15 exons and their flanking regions of the TNNT2 gene were analyzed by DNA sequence analysis in 174 patients with HCM and DCM diagnosis. We identified genetic variations in TNNT2 exon regions in 56 patients and genetic variations in TNNT2 intron regions in 164 patients. Two patients were found to carry unique mutations in the TNNT2 gene. Limited genetic screening analysis is not suitable for routine testing of disease-causing mutations in patients with HCM and DCM as only individual mutation-positive cases may be identified. Therefore, this approach cannot be recommended for daily clinical practice even though, due to financial constraints, it currently represents the only available strategy in a majority of cardio-centers.