In deafness, which is caused by the malfunctioning of the inner ear, an implantation of a cochlear implant (CI) is able to restore hearing. The CI is a neural prosthesis that is located within the cochlea. It replaces the function of the inner hair cells by direct electrical stimulation of the auditory nerve fibers. The CI enables many deaf or severe hearing-impaired people to achieve a good speech perception. Nevertheless, there is a lot of potential for further improvements. Compared to normal-hearing listeners rate pitch discrimination is much worse. Rate pitch discrimination is the ability to distinguish the pitch of two stimuli with two different pulse rates. This ability is important for enjoying music as well as speech perception (in noise). Further, the small dynamic range in electrical hearing (compared to normal-hearing listeners) and therefore the small intensity resolution limits the performance of CI users. Both, rate pitch coding and dynamic range were investigated in this doctoral thesis. For the first issue, a pitch discrimination task was designed to determine the just-noticeable-difference (JND) in pitch with 200 and 400 pps as reference. Additionally to the default biphasic pulse (single pulse) the experiment was performed with double pulses. The double pulse consists out of two biphasic pulses directly after each other and a small interpulse interval (IPI) in between. Three different IPIs (15, 50, and 150 µs) were tested. The statistical analysis of JNDs revealed no significant effects between stimulation with single-pulse or double-pulse trains. A follow-up study investigated an alternating pulse train consisting of single and double pulses. To investigate if the 400 pps alternating pulse train is comparable in pitch with the 400 pps single-pulse train, a pairwise pitch comparison test was conducted. The alternating pulse train was compared with single-pulse trains at 200, 300 and 400 pps. The results showed that the alternating pulse train is for most subjects similar in pitch with the 200 pps single-pulse train. Therefore, pitch perception seemed to be dominated by the double pulses within the pulse train. Accordingly, double pulses with different amplitudes were tested. Based on the facilitation effect, a larger neuronal response was expected by stimulating with two pulses with a short IPI within the temporal facilitation range. In other studies, this effect was shown to be maximal in CIs of the manufacturer Cochlear, with first pulse amplitudes set at or slightly below the electrically evoked compound action potential (ECAP) threshold. The second pulse amplitude did not influence the facilitation effect and therefore could be choose at will. Similarly, this effect was tested in this thesis with CIs of the manufacturer MED-EL. Nevertheless, to achieve a proper signal-to-noise ratio, technical issues had to be addressed like a high noise floor, resulting in incorrect determination of the ECAP threshold. After solving this issues, the maximum facilitation effect was around the ECAP threshold as in the previous study with Cochlear. For future studies this effect could be used in a modified double pulse rate pitch experiment with the first pulse amplitude at ECAP threshold and the second pulse amplitude variable to set the most comfortable loudness level (MCL). The last study within this thesis investigated the loudness perception at two different loudness levels and the resulting dynamic range for different interphase-gaps (IPG). A larger IPG can reduce the amplitude at same loudness level to save battery power. However, it was unknown if the IPG has an influence on the dynamic range. Different IPGs (10 and 30 µs) were compared with the default IPG (2.1 µs) in a loudness matching experiment. The experiment was performed at the most comfortable loudness level (MCL) of the subject and the amplitude of half the dynamic range (50%-ADR). An upper dynamic range was calculated from the results of MCL and 50%-ADR (therefore not the whole dynamic range was covered). As expected from previous studies a larger IPG resulted in smaller amplitudes. However, the observed effect was larger at MCL than at 50%-ADR which resulted in a smaller upper dynamic range. This is the first time a decrease of this dynamic range was shown. / Bei einer Taubheit, welche durch eine Schädigung des Innenohres hervorgerufen wird, ist es möglich das Gehör mittels eines Cochlea-Implantates (CI) wieder herzustellen. Das Implantat befindet sich innerhalb der Hörschnecke und ist in der Lage, die Funktion der inneren Haarzellen zu ersetzen. Dies geschieht durch direkte elektrische Stimulation der auditorischen Nervenfasern. Dadurch ermöglicht das CI Ertaubten oder stark Schwerhörigen, ein gutes Sprachverstehen zu erlangen. Dennoch gibt es weiterhin Verbesserungspotential. Im Vergleich zu Normalhörenden ist unter anderem die Tonhöhenunterscheidung stark eingeschränkt. Die Unterscheidung von Tonhöhen ist sowohl für den Musikgenuss als auch für das Sprachverstehen (im Störgeräusch) wichtig. Ebenso verfügen CI Träger über einen vergleichsweise kleinen Dynamikbereich und einer daraus resultierenden geringen Auflösung der Intensitäten. Dies kann zu einer Beeinträchtigung des Hörens führen. Sowohl die Fähigkeit der Tonhöhenunterscheidung als auch der Dynamikbereich werden in der vorliegenden Doktorarbeit untersucht. Hierfür wurde zunächst ein Tonhöhenunterscheidungs-Experiment entworfen, bei welchem der kleinste wahrnehmbare Unterschied zweier Pulsraten ermittelt wurde. Die Pulsraten 200 und 400 pps dienten als Referenzwert. Neben dem standardmäßig verwendeten Biphasischen Puls, wurden Doppelpulse genutzt. Diese bestehen aus zwei aufeinander folgenden biphasischen Pulsen gleicher Amplitude, welche durch ein kurzes interpuls Intervall (IPI) separiert sind. In dem Experiment wurden drei unterschiedliche IPIs getestet (15, 50 und 150 µs). Die Analyse des kleinesten wahrnehmbaren Tonhöhenunterschieds ergab keine signifikanten Unterschiede zwischen dem einfachen Puls und den Doppelpulsen. Ein Folgeexperiment beschäftigte sich mit einer alternierenden Pulsfolge bestehend aus dem einfachen und dem Doppelpuls. In einem paarweisen Vergleichsexperiment wurde die alternierende Pulsfolge bei 400 pps mit einem Einfachpuls bei 200, 300 und 400 pps in ihrer Tonhöhe verglichen. Es zeigte sich, dass die alternierende Pulsfolge bei 400 pps mehrheitlich mit dem Einzelpuls bei 200 pps vergleichbar war. Demzufolge scheint die Tonhöhenwahrnehmung der alternierenden Pulsfolge von dem Doppelpuls dominiert zu werden. Auf beide Experimente aufbauend, wurden Doppelpulse mit unterschiedlichen Amplituden untersucht. Basierend auf den Bahnungseffekt (Facilitation-Effekt), kann eine größere neuronale Antwort hervorgerufen werden, indem mit Doppelpulsen mit kurzem IPI stimuliert wird. In einer anderen Studie konnte anhand von CIs der Firma Cochlear gezeigt werden, dass dieser Effekt maximal war, wenn die Amplitude des ersten Pulses nahe der Schwelle zum elektrisch evozierten Summenaktionspotential (ECAP) liegt. Die Amplitude des zweiten Pulses dagegen hatte keinen Einfluss auf den „Facilitation“-Effekt und konnte beliebig gewählt werden. Dieser Effekt wurde mit CIs der Firma MED-EL in der vorliegenden Doktorarbeit nachgestellt. Es zeigte sich, dass auch hier der größte „Facilitation“-Effekt auftrat, wenn die Amplitude des ersten Pulses nahe der ECAP-Schwelle lag. In zukünftigen Studien könnte dieser Effekt für einen modifizierten Doppelpuls genutzt werden, um mit diesem das ursprüngliche Tonhöhenunterscheidungs-Experiment zu wiederholen. Dabei würde die Amplitude des ersten Pulses der ECAP-Schwelle entsprechen, während die zweite Pulsamplitude variiert wird, um den größten, möglichst angenehmen, Lautheitspegel zu erhalten. In einer letzten Studie wurde das Lautheitsempfinden bei zwei unterschiedlichen Lautheiten bei unterschiedlichen Interphasen-Gaps (IPG) untersucht und der daraus resultierende Dynamikbereich. Eine Vergrößerung des IPGs führt bei gleich bleibendem Lautheitsempfinden zu geringeren Stimulations-Amplituden und ist dadurch in der Lage die Batterie schonen. Allerdings ist der Einfluss auf den Dynamikbereich bisher unbekannt. In einem Lautheits-Experiment wurden Pulse mit verschiedenen IPGs (10 und 30 µs) mit dem standardmäßig verwendeten IPG (2.1 µs) in ihrer Lautheit angeglichen. Dieses Verfahren wurde bei MCL und der Amplitude des halben Dynamikbereichs (50%-ADR) durchgeführt. Aus den ermittelten Werten konnte ein „oberer“ Dynamikbereich zwischen MCL und 50%-ADR ermittelt werden. Es zeigte sich, dass sich die Amplituden mit größerem IPG, wie erwartet, verringerten. Jedoch zeigte sich ein stärkerer Effekt bei MCL, was eine Verringerung des Dynamikbereichs zur Folge hat. Dies ist das erste Mal, dass eine Verringerung des Dynamikbereichs gezeigt wurde.

Background: Vagus nerve stimulation is increasingly applied to treat epilepsy, psychiatric conditions and potentially chronic heart failure. After implanting vagus nerve electrodes to the cervical vagus nerve, side effects such as voice alterations and dyspnea or missing therapeutic effects are observed at different frequencies. Cervical vagus nerve branching might partly be responsible for these effects. However, vagus nerve branching has not yet been described in the context of vagus nerve stimulation. Materials and methods: Branching of the cervical vagus nerve was investigated macroscopically in 35 body donors (66 cervical sides) in the carotid sheath. After X-ray imaging for determining the vertebral levels of cervical vagus nerve branching, samples were removed to confirm histologically the nerve and to calculate cervical vagus nerve diameters and cross-sections. Results: Cervical vagus nerve branching was observed in 29%of all cases (26% unilaterally, 3% bilaterally) and proven histologically in all cases. Right-sided branching (22%) was more common than left-sided branching (12%) and occurred on the level of the fourth and fifth vertebra on the left and on the level of the second to fifth vertebra on the right side. Vagus nerves without branching were significantly larger than vagus nerves with branches, concerning their diameters (4.79mm vs. 3.78mm) and cross-sections (7.24 mm2 vs. 5.28mm2). Discussion: Cervical vagus nerve branching is considerably more frequent than described previously. The side-dependent differences of vagus nerve branching may be linked to the asymmetric effects of the vagus nerve. Cervical vagus nerve branching should be taken into account when identifying main trunk of the vagus nerve for implanting electrodes to minimize potential side effects or lacking therapeutic benefits of vagus nerve stimulation.

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than fullsine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the halfsegment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.

In the nature, crayfish are represented like predators or a part of food base of some fish. Also in free waters they acts as detrivors and are an important element in the nutrient and energy circle in aquatic ecosystem. The crayfish weren't able to avoid negative impacts of anthropogenic activities such as water pollution and devastation of habitats. For these reasons reproduction of the crayfish is necessary in hatcheries and farms. The main aim of my work was to study the reproductive biology of the crayfish focused on the process of mating, the interval between mating and laying eggs, fertilization and morphological structure of the male and female gametes. Among the secondary objectives there was included using of repeated electrostimulation of the crayfish and the possibility of hybrids of the noble crayfish (Astacus astacus) and the narrow-clawed crayfish (Astacus leptodactylus). The observation of the period of reproduction was realized on representativies of the noble crayfish and the narrow-clawed crayfish throughout natural mating in the tanks. The structure of gametes was observed on the samples taken from thenoble crayfish (Astacus astacus), the narrow-clawed crayfish (Astacus leptodactylus), the signal crayfish (Pacifastacus leniusculus), the red swamp crayfish (Procambarus clarkii) and spinycheek crayfish (Orconectes limosus). The experiments were carried out during the autumn season in 2012 and 2013. The results of observations of the reproduction of crayfish made us clear as for the period and intervals for all phases of the process of mating crayfish. For females the noble crayfish and the narrow-clawed crayfish was found oviposition without the presence of males. Their individual components have been described by using ultrastructure of males and female gametes. Repeated electrostimulation showed at the family Astacidae as a suitable tool for collecting large mass of sperm material. Hybridization experiment proved that it can occur to mate the two species of crayfish in areas where they occur simultaneously. These experiments helped to further knowledge of reproductive biology of crayfish.

Background: Vagus nerve stimulation is increasingly applied to treat epilepsy, psychiatric conditions and potentially chronic heart failure. After implanting vagus nerve electrodes to the cervical vagus nerve, side effects such as voice alterations and dyspnea or missing therapeutic effects are observed at different frequencies. Cervical vagus nerve branching might partly be responsible for these effects. However, vagus nerve branching has not yet been described in the context of vagus nerve stimulation. Materials and methods: Branching of the cervical vagus nerve was investigated macroscopically in 35 body donors (66 cervical sides) in the carotid sheath. After X-ray imaging for determining the vertebral levels of cervical vagus nerve branching, samples were removed to confirm histologically the nerve and to calculate cervical vagus nerve diameters and cross-sections. Results: Cervical vagus nerve branching was observed in 29%of all cases (26% unilaterally, 3% bilaterally) and proven histologically in all cases. Right-sided branching (22%) was more common than left-sided branching (12%) and occurred on the level of the fourth and fifth vertebra on the left and on the level of the second to fifth vertebra on the right side. Vagus nerves without branching were significantly larger than vagus nerves with branches, concerning their diameters (4.79mm vs. 3.78mm) and cross-sections (7.24 mm2 vs. 5.28mm2). Discussion: Cervical vagus nerve branching is considerably more frequent than described previously. The side-dependent differences of vagus nerve branching may be linked to the asymmetric effects of the vagus nerve. Cervical vagus nerve branching should be taken into account when identifying main trunk of the vagus nerve for implanting electrodes to minimize potential side effects or lacking therapeutic benefits of vagus nerve stimulation.

In der vorliegenden Arbeit wurden einseitig mit Human-Cochlea-Implantat versorgte Meerschweinchen verwendet, die auf dem anderen Ohr normalhörend waren und mit einer einseitig vertäubten, aber nicht elektrostimulierten Kontrollgruppe verglichen wurden. Untersucht wurde der Einfluss von drei unterschiedlichen Stimulationsraten und drei Stimulationsintensitäten während einer einseitigen Elektrostimulation. Dabei wurde zunächst der Einfluss der Elektrostimulation auf die Hörschwellen mittels Hirnstammaudiometrie (ABR) untersucht. Anschließend wurden die Zelldichten in der aufsteigenden Hörbahn (dorsaler Nucleus Cochlearis, Colliculus Inferior, medialer Kniehöcker und auditorischer Cortex) im Hirnschnitt unter Verwendung einer Hämalaun-Eosin Färbung bestimmt. Ein Zusammenhang zwischen der verwendeten Stimulationsrate und den in der zentralen Hörbahn gefundenen Zelldichten wurde ebenso wenig gezeigt wie ein Zusammenhang mit den mittels ABR ermittelten Hörschwellen der normalhörenden Seite. Dagegen wurde jedoch ein Zusammenhang zwischen den in der Elektrostimulation verwendeten Stimulationsintensitäten und den ermittelten Zelldichten festgestellt. Die niedrigste verwendete Stimulationsintensität führte zu einer bilateralen Konservierung der Zelldichten in der gesamten untersuchten Hörbahn, wogegen eine Elektrostimulation mit der höchsten Stimulationsintensität zum Teil einen bilateralen Zellverlust im dorsalen Nucleus Cochlearis, medialen Kniehöcker und im auditorischen Cortex zur Folge hatte. Dieser Zellverlust führte in dem Untersuchungszeitraum nicht zu einer signifikanten Veränderung der Hörschwelle. / In this study, human cochlear implants (CI) were implanted unilaterally in the cochlea of guinea pigs that were normal hearing on the contralateral side. Electro-stimulation was used on the cochlea with the implanted CI. They were compared to an unilaterally implanted but not electro-stimulated control group. This study investigates the effect of three different stimulation-rates and three different stimulation-intensities in unilateral electro-stimulation. The effect of the electro-stimulation on the hearing thresholds was determined using auditory brainstem recordings (ABR). Afterwards, cell densities in the ascending auditory pathway (dorsal cochlear nucleus, inferior colliculus, medial geniculate body and auditory cortex) were measured in brain slices stained with hematoxylin and eosin. No evidence was found of a connection between the different stimulation rates of electro-stimulation in the cochlea with a CI and cell densities seen in the central auditory pathway. Furthermore, there were no links found between hearing thresholds determined by ABR and the different parameters that were used for the electro-stimulation. However a significant effect of the different stimulation intensities on the cell densities identified in the auditory pathway was demonstrated. The lowest intensity used in the electro stimulation led to a bilateral preservation of cell densities in the entire auditory pathway whereas electro-stimulation with the highest intensity induced a significant cell loss in the auditory pathway (dorsal cochlear nucleus, the medial geniculate body and the auditory cortex). Interestingly, this cell loss was not accompanied by significant changes in the auditory threshold.

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than fullsine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the halfsegment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.