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Aliuos P.,Hannover Medical School | Schulze J.,Hannover Medical School | Schomaker M.,Laser Zentrum Hannover e.V. | Reuter G.,Hannover Medical School | And 6 more authors.
PLoS ONE | Year: 2016

Introduction Long-term drug delivery to the inner ear may be achieved by functionalizing cochlear implant (CI) electrodes with cells providing neuroprotective factors. However, effective strategies in order to coat implant surfaces with cells need to be developed. Our vision is to make benefit of electromagnetic field attracting forces generated by CI electrodes to bind BDNF-secreting cells that are labelled with magnetic beads (MB) onto the electrode surfaces. Thus, the effect of MB-labelling on cell viability and BDNF production were investigated. Materials and Methods Murine NIH 3T3 fibroblasts-genetically modified to produce BDNF-were labelled with MB. Results Atomic force and bright field microscopy illustrated the internalization of MB by fibroblasts after 24 h of cultivation. Labelling cells with MB did not expose cytotoxic effects on fibroblasts and allowed adhesion on magnetic surfaces with sufficient BDNF release. Discussion Our data demonstrate a novel approach for mediating enhanced long-term adhesion of BDNF-secreting fibroblasts on model electrode surfaces for cell-based drug delivery applications in vitro and in vivo. This therapeutic strategy, once transferred to cells suitable for clinical application, may allow the biological modifications of CI surfaces with cells releasing neurotrophic or other factors of interest. © 2016 Aliuos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Lange F.,Hannover Medical School | Seer C.,Hannover Medical School | Finke M.,Cluster of Excellence Hearing4all | Finke M.,Hannover Medical School | And 2 more authors.
Biological Psychology | Year: 2015

Sokolov distinguished between reactive and proactive variants of the orienting response (OR). The Novelty P3 is considered as an electrophysiological signature of the reactive OR. Recent work suggests that the proactive OR is reflected in frontally distributed P3 activity elicited by uncertainty-reducing stimuli in task-switching paradigms. Here, we directly compare the electrophysiological signatures of reactive and proactive ORs. Participants completed a novelty oddball task and a task-switching procedure while the electroencephalogram was measured. Novel and uncertainty-reducing stimuli evoked prominent fronto-centrally distributed Novelty P3 and Uncertainty P3 waves, respectively. We found a substantial negative correlation between Novelty P3 and Uncertainty P3 across participants, suggesting that reactive and proactive ORs converge on a common neural pathway, but also that distinguishable routes to orienting exist. Moreover, response accuracy was associated with reduced Novelty-P3 and enhanced Uncertainty-P3 amplitudes. The relation between Novelty P3 and Uncertainty P3 might serve as an index of individual differences in distractibility and cognitive control. © 2015 Elsevier B.V.All rights reserved. Source


Roy A.T.,Johns Hopkins Hospital | Penninger R.T.,Leibniz University of Hanover | Pearl M.S.,Harvard University | Wuerfel W.,Johns Hopkins University | And 4 more authors.
Otology and Neurotology | Year: 2016

Background: Cochlear implant (CI) electrode arrays typically do not reach the most apical regions of the cochlea that intrinsically encode low frequencies. This may contribute to diminished implant-mediated musical sound quality perception. The objective of this study was to assess the effect of varying degrees of apical cochlear stimulation (measured by angular insertion depth) on musical sound quality discrimination. Hypothesis: Increased apical cochlear stimulation will improve low-frequency perception and musical sound quality discrimination. Methods: Standard (31.5 mm, n=17) and medium (24 mm, n=8) array Med-EL CI users, and normal hearing (NH) listeners (n=16) participated. Imaging confirmed angular insertion depth. Participants completed a musical discrimination task in which they listened to a real-world musical stimulus (labeled reference) and provided sound quality ratings to versions of the reference, which included a hidden reference and test stimuli with increasing amounts of lowfrequency removal. Scores for each CI users were calculated on the basis of how much their ratings differed from NH listeners for each stimulus version. Results: Medium array and standard users had significantly different insertion depths (389.464.5 and 583.978.5 degrees, respectively; p<0.001). A significant Pearson's correlation was observed between angular insertion depth and the hidden reference scores ( p<0.05). Conclusion: CI users with greater apical stimulation made sound quality discriminations that more closely resembled those of NH controls for stimuli that contained low frequencies (<200 Hz of information). These findings suggest that increased apical cochlear stimulation improves musical low-frequency perception, which may provide a more satisfactory music listening experience for CI users. Copyright © 2015 Otology &Neurotology, Inc. Source


Timm L.,Hannover Medical School | Vuust P.,University of Aarhus | Vuust P.,The Royal Academy of Music | Brattico E.,Aalto University | And 7 more authors.
Frontiers in Human Neuroscience | Year: 2014

Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 min. The presentation of stimuli did not require the participants' attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients' age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. Highlights: - Automatic brain responses to musical feature changes reflect the limitations of central auditory processing in adult Cochlear Implant users. - The brains of adult CI users automatically process sound features changes even when inserted in a musical context. - CI users show disrupted automatic discriminatory abilities for rhythm in the brain. - Our fast paradigm demonstrate residual musical abilities in the brains of adult CI users giving hope for their future rehabilitation. © 2014 Timm, Vuust, Brattico, Agrawal, Debener, Büchner, Dengler and Wittfoth. Source


Carroll R.,Cluster of Excellence Hearing4all | Carroll R.,University of Oldenburg | Meis M.,Cluster of Excellence Hearing4all | Schulte M.,Cluster of Excellence Hearing4all | And 3 more authors.
International Journal of Audiology | Year: 2015

Objective: To report the development of a standardized German version of a reading span test (RST) with a dual task design. Special attention was paid to psycholinguistic control of the test items and time-sensitive scoring. We aim to establish our RST version to use for determining an individual's working memory in the framework of hearing research in German contexts. Design: RST stimuli were controlled and pretested for psycholinguistic factors. The RST task was to read sentences, quickly determine their plausibility, and later recall certain words to determine a listener's individual reading span. RST results were correlated with outcomes of additional sentence-in-noise tests measured in an aided and an unaided listening condition, each at two reception thresholds. Study sample: Item plausibility was pre-determined by 28 native German participants. An additional 62 listeners (45-86 years, M=69.8) with mild-to-moderate hearing loss were tested for speech intelligibility and reading span in a multicenter study. Results: The reading span test significantly correlated with speech intelligibility at both speech reception thresholds in the aided listening condition. Conclusion: Our German RST is standardized with respect to psycholinguistic construction principles of the stimuli, and is a cognitive correlate of intelligibility in a German matrix speech-in-noise test. © 2015 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society. Source

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