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Pulsars (in short for Pulsating Stars) are magnetized, fast rotating neutron stars. The basic picture of a pulsar describes it as a neutron star which has a rotation axis that is not aligned with its magnetic field axis. The emission is assumed to be generated near the magnetic poles of the neutron star and emitted along the open magnetic field lines. Consequently, the corresponding beam of photons is emitted along the magnetic field line axis. The non-alignment of both, the rotation and the magnetic field axis, results in the effect that the emission of the pulsar is only seen if its beam points towards the observer.
The emission from a pulsar is therefore perceived as being pulsed although its generation is not. This rather simple geometrical model is commonly referred to as Lighthouse Model and has been widely accepted. However, it does not deliver an explanation of the precise mechanisms behind the emission from pulsars (see below for more details).
Nowadays more than 2000 pulsars are known. They are observed at various wavelengths. Multiwavelength studies have shown that some pulsars are visible only at certain wavelengths while the emission from others can be observed throughout large parts of the electromagnetic spectrum. An example of the latter case is the Crab pulsar which is also the main object of interest in this thesis. Originating from a supernova explosion observed in 1054 A.D. and discovered in 1968, the Crab pulsar has been the central subject of numerous studies. Its pulsed emission is visible throughout the whole electromagnetic spectrum which makes it a key figure in understanding the possible mechanisms of multiwavelength emission from pulsars.
The Crab pulsar is also well known for its radio emission strongly varying on long as well as on short time scales. While long time scale behaviour from a pulsar is usually examined through the use of its average profile (a profile resulting from averaging of a large number of individual pulses resulting from single rotations), short time scale behaviour is examined via its single pulses. The short time scale anomalous behaviour of its radio emission is commonly referred to as Giant Pulses and represents the central topic of this thesis.
While current theoretical approaches place the origin of the radio emission from a pulsar like the Crab near its magnetic poles (Polar Cap Model) as already indicated by the Lighthouse model, its emission at higher frequencies, especially its gamma-ray emission, is assumed to originate further away in the geometrical region surrounding a pulsar which is commonly referred to as a pulsar magnetosphere (Outer Gap Model). Consequently, the respective emission regions are usually assumed not to be connected. However, past observational results from the Crab pulsar represent a contradiction to this assumption.
Radio giant pulses from the Crab pulsar have been observed to emit large amounts of energy on very short time scales implying small emission regions on the surface of the pulsar. Such energetic events might also leave a trace in the gamma-ray emission of the Crab pulsar.
The aim of this thesis is to search for this connection in the form of a correlation study between radio giant pulses and gamma-photons from the Crab pulsar.
To make such a study possible, a multiwavelength observational campaign was organized for which radio observations were independently applied for, coordinated and carried out with the Effelsberg radio telescope and the Westerbork Synthesis Radio Telescope and gamma-ray observations with the Major Atmospheric Imaging Cherenkov telescopes. The corresponding radio and gamma-ray data sets were reduced and the correlation analysis thereafter consisted of three different approaches:
1) The search for a clustering in the differences of the times of arrival of radio giant pulses and gamma-photons;
2) The search for a linear correlation between radio giant pulses and gamma-photons using the Pearson correlation approach;
3) A search for an increase of the gamma-ray flux around occurring radio giant pulses.
In the last part of the correlation study an increase of the number of gamma-photons centered on a radio giant pulse by about 17% (in contrast with the number of gamma-photons when no radio giant pulse occurs in the same time window) was discovered. This finding suggests that a new theoretical approach for the emission of young pulsars like the Crab pulsar, is necessary.
In this thesis, I present a model system for carbohydrate interactions with single-crystalline Ru surfaces. Geometric and electronic properties of copper phthalocyanine (CuPc) on top of graphene on hexagonal Ru(0001), rectangular Ru(10-10) and vicinal Ru(1,1,-2,10) surfaces have been studied. First, the Fermi surfaces and band structures of the three Ru surfaces were investigated by high-resolution angle-resolved photoemission spectroscopy. The experimental data and theoretical calculations allow to derive detailed information about the momentum-resolved electronic structure. The results can be used as a reference to understand the chemical and catalytic properties of Ru surfaces. Second, graphene layers were prepared on the three different Ru surfaces. Using low-energy electron diffraction and scanning tunneling microscopy, it was found that graphene can be grown in well-ordered structures on all three surfaces, hexagonal Ru(0001), rectangular Ru(10-10) and vicinal Ru(1,1,-2,10), although they have different surface symmetries. Evidence for a strong interaction between graphene and Ru surfaces is a 1.3-1.7e V increase in the graphene pi-bands binding energy with respect to free-standing graphene sheets. This energy variation is due to the hybridization between the graphene pi bands and the Ru 4d electrons, while the lattice mismatch does not play an important role in the bonding between graphene and Ru surfaces. Finally, the geometric and electronic structures of CuPc on Ru(10-10), graphene/Ru(10-10), and graphene/Ru(0001) have been studied in detail. CuPc molecules can be grown well-ordered on Ru(10-10) but not on Ru(0001). The growth of CuPc on graphene/Ru(10-10) and Ru(0001) is dominated by the Moire pattern of graphene. CuPc molecules form well-ordered structures with rectangular unit cells on graphene/Ru(10-10) and Ru(0001). The distance of adjacent CuPc molecules is 1.5 and 1.3 nm on graphene/Ru(0001) and 1.54 and 1.37 nm on graphene/Ru(10-10). This indicates that the molecule-substrate interaction dominates over the intermolecular interaction for CuPc molecules on graphene/Ru(10-10) and graphene/Ru(0001).
The learned helplessness phenomenon is a specific animal behavior induced by prior exposure to uncontrollable aversive stimuli. It was first found by Seligman and Maier (1967) in dogs and then has been reported in many other species, e.g. in rats (Vollmayr and Henn, 2001), in goldfishes (Padilla, 1970), in cockroaches (Brown, 1988) and also in fruit flies (Brown, 1996; Bertolucci, 2008). However, the learned helplessness effect in fruit flies (Drosophila melanogaster) has not been studied in detail. Thus, in this doctoral study, we investigated systematically learned helplessness behavior of Drosophila for the first time.
Three groups of flies were tested in heatbox. Control group was in the chambers experiencing constant, mild temperature. Second group, master flies were punished in their chambers by being heated if they stopped walking for 0.9s. The heat pulses ended as soon as they resumed walking again. A third group, the yoked fly, was in their chambers at the same time. However, their behavior didn’t affect anything: yoked flies were heated whenever master flies did, with same timing and durations. After certain amount of heating events, yoked flies associated their own behavior with the uncontrollability of the environment. They suppressed their innate responses such as reducing their walking time and walking speed; making longer escape latencies and less turning around behavior under heat pulses. Even after the conditioning phase, yoked flies showed lower activity level than master and control flies. Interestingly, we have also observed sex dimorphisms in flies. Male flies expressed learned helplessness not like female flies. Differences between master and yoked flies were smaller in male than in female flies. Another interesting finding was that prolonged or even repetition of training phases didn’t enhance learned helplessness effect in flies.
Furthermore, we investigated serotonergic and dopaminergic nervous systems in learned helplessness. Using genetic and pharmacological manipulations, we altered the levels of serotonin and dopamine in flies’ central nervous system. Female flies with reduced serotonin concentration didn’t show helpless behavior, while the learned helplessness effect in male flies seems not to be affected by a reduction of serotonin. Flies with lower dopamine level do not display the learned helplessness effect in the test phase, suggesting that with low dopamine the motivational change in learned helplessness in Drosophila may decline faster than with a normal dopamine level.
Several aspects of the stability analysis of large-scale discrete-time systems are considered. An important feature is that the right-hand side does not have have to be continuous.
In particular, constructive approaches to compute Lyapunov functions are derived and applied to several system classes.
For large-scale systems, which are considered as an interconnection of smaller subsystems, we derive a new class of small-gain results, which do not require the subsystems to be robust in some sense. Moreover, we do not only study sufficiency of the conditions, but rather state an assumption under which these conditions are also necessary.
Moreover, gain construction methods are derived for several types of aggregation, quantifying how large a prescribed set of interconnection gains can be in order that a small-gain condition holds.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of the brain, which is characterized by a progressive loss of memory and spatial orientation. Only less than 5-10% of AD sufferers are familial cases due to genetic mutations in the amyloid precursor protein (APP) gene or presenilin (PS) 1 and 2 genes. The cause of sporadic AD (sAD) which covers > 95% of AD patients is still unknown. Current research found interactions between aging, diabetes and cognitive decline including dementia in general and in AD in particular. Disturbances of brain glucose uptake, glucose tolerance and utilization and impairment of the insulin/insulin receptor (IR) signaling cascade are thought to be key targets for the development of sAD.
In the brain of AD patients, neural plasticity is impaired indicated by synaptic and neuronal loss. Adult neurogenesis (AN), the generation of functional neurons in the adult brain, may be able to restore neurological function deficits through the integration of newborn neurons into existing neural networks. The dentate gyrus of the hippocampus is one out of few brain regions where life-long AN exists. However, there is a big controversy in literature regarding the involvement of AN in AD pathology. Most animal studies used transgenic mice based on the Amyloid ß (Aß) hypothesis which primarily act as models for the familial form of AD. Findings from human post mortem AN studies were also inconstistent. In this thesis, we focused on the possible involvement of AN in the pathogenesis of the sporadic form of AD. Streptozotocin intracerebroventricularily (STZ icv) treated rats, which develop an insulin-resistant brain state and learning and memory deficits preceding Aß pathology act as an appropriate animal model for sAD. We used STZ treatment for both parts of my work, for the in vivo and in vitro study.
In the first part of my thesis, my coworkers and I investigated STZ icv treatment effects on different stages of AN in an in vivo approach. Even if STZ icv treatment does not seem to considerably influence stem cell proliferation over a short-term (1 month after STZ icv treatment) as well as in a long-term (3 months after STZ icv treatment) period, it results in significantly less immature and newborn mature neurons 3 months after STZ icv treatment. This reduction detected after 3 months was specific for the septal hippocampus, discussed to be important for spatial learning. Subsequently we performed co-localization studies with antibodies detecting BrdU (applied appr. 27 days before sacrifice) and cell-type specific markers such as NeuN, and GFAP, we found that STZ treatment does not affect the differentiation fate of newly generated cells. Phenotype analysis of BrdU-positive cells in the hilus and molecular layer revealed that some of the BrdU-positive cells are newborn oligodendrocytes but not newborn microglia.
In the second part of my thesis I worked with cultured neural stem cells (NSCs) isolated from the adult rat hippocampus to reveal STZ effects on the proliferation of of NSCs, and on the survival and differentiation of their progeny. Furthermore, this in vitro approach enabled me to study cellular mechanisms underlying the observed impaired neurogenesis in the hippocampus of STZ-treated rats. In contrast to our findings of the STZ icv in vivo study we revealed that STZ supplied with the cell culture medium inhibits the proliferation of NSCs in a dose-dependent and time-dependent manner. Moreover, performing immunofluorescence studies with antibodies detecting cell-type specific markers after triggering NSCs to differentiate, we could show that STZ treatment affects the number of newly generated neurons but not of astrocytes. Analyzing newborn cells starting to differentiate and migrate I was able to demonstrate that STZ has no effect on the migration of newborn cells. Trying to reveal cellular mechanisms underlying the negative influence of STZ on hippocampal AN, we performed qRT-PCR and immunofluorescence staining and thus could show that in NSCs the expression of glucose transporter (GLUT)3 mRNA as well as IR and GLUT3 protein levels are reduced after STZ treatment. Therefore, the inhibition of the proliferation of NSCs may be (at least partially) caused by these two molecules. Interestingly, the effect of STZ on differentiating cells was shown to be different, as IR protein expression was not significantly changed but GLUT3 protein levels were decreased in consequence of STZ treatment.
In summary, this project delivered further insights into the interrelation between AN the sporadic form of sAD and thus provides a basis of new therapeutic approaches in sAD treatment through intervening AN. Discrepancies between the results of the two parts of my thesis, the in vivo and in vitro part, were certainly caused to a certain extent by the missing microenvironment in the in vitro approach with cultured NSCs. Future studies e.g. using co-culture systems could at least minimize the effect of a missing natural microenvironment of cultured NSCs, so that the use of an in vitro approach for the investigation of STZ treatment underlying cellular mechanisms can be improved.
Analysis of discretization schemes for Fokker-Planck equations and related optimality systems
(2015)
The Fokker-Planck (FP) equation is a fundamental model in thermodynamic kinetic theories and
statistical mechanics.
In general, the FP equation appears in a number of different fields in natural sciences, for instance in solid-state physics, quantum optics, chemical physics, theoretical biology, and circuit theory. These equations also provide a powerful mean to define
robust control strategies for random models. The FP equations are partial differential equations (PDE) describing the time evolution of the probability density function (PDF) of stochastic processes.
These equations are of different types depending on the underlying stochastic process.
In particular, they are parabolic PDEs for the PDF of Ito processes, and hyperbolic PDEs for piecewise deterministic processes (PDP).
A fundamental axiom of probability calculus requires that the integral of the PDF over all the allowable state space must be equal to one, for all time. Therefore, for the purpose of accurate numerical simulation, a discretized FP equation must guarantee conservativeness of the total probability. Furthermore, since the
solution of the FP equation represents a probability density, any numerical scheme that approximates the FP equation is required to guarantee the positivity of the solution. In addition, an approximation scheme must be accurate and stable.
For these purposes, for parabolic FP equations on bounded domains, we investigate the Chang-Cooper (CC) scheme for space discretization and first- and
second-order backward time differencing. We prove that the resulting
space-time discretization schemes are accurate, conditionally stable, conservative, and preserve positivity.
Further, we discuss a finite difference discretization for the FP system corresponding to a PDP process in a bounded domain.
Next, we discuss FP equations in unbounded domains.
In this case, finite-difference or finite-element methods cannot be applied. By employing a suitable set of basis functions, spectral methods allow to treat unbounded domains. Since FP solutions decay exponentially at infinity, we consider Hermite functions as basis functions, which are Hermite polynomials multiplied by a Gaussian.
To this end, the Hermite spectral discretization is applied
to two different FP equations; the parabolic PDE corresponding to Ito processes, and the system of hyperbolic PDEs corresponding to a PDP process. The resulting discretized schemes are analyzed. Stability and spectral accuracy of the Hermite spectral discretization of the FP problems is proved. Furthermore, we investigate the conservativity of the solutions of FP equations discretized with the Hermite spectral scheme.
In the last part of this thesis, we discuss optimal control problems governed by FP equations on the characterization of their solution by optimality systems. We then investigate the Hermite spectral discretization of FP optimality systems in unbounded domains.
Within the framework of Hermite discretization, we obtain sparse-band systems of ordinary differential equations. We analyze the accuracy of the discretization schemes by showing spectral convergence in approximating the state, the adjoint, and the control variables that appear in the FP optimality systems.
To validate our theoretical estimates, we present results of numerical experiments.
Division of labor represents a major advantage of social insect communities that accounts for their enormous ecological success. In colonies of the honeybee, Apis mellifera, division of labor comprises different tasks of fertile queens and drones (males) and, in general, sterile female workers. Division of labor also occurs among workers in form of an age-related polyethism. This helps them to deal with the great variety of tasks within the colony. After adult eclosion, workers spend around three weeks with various duties inside the hive such as tending the brood or cleaning and building cells. After this period workers switch to outdoor tasks and become foragers collecting nectar, pollen and water. With this behavioral transition, workers face tremendous changes in their sensory environment. In particular, visual sensory stimuli become important, but also the olfactory world changes. Foragers have to perform a completely new behavioral repertoire ranging from long distance navigation based on landmark orientation and polarized-skylight information to learning and memory tasks associated with finding profitable food sources. However, behavioral maturation is not a purely age-related internal program associated with a change, for example, in juvenile hormone titers. External factors such as primer pheromones like the brood pheromone or queen mandibular pheromone can modulate the timing of this transition. In this way colonies are able to flexibly adjust their work force distribution between indoor and outdoor tasks depending on the actual needs of the colony. Besides certain physiological changes, mainly affecting glandular tissue, the transition from indoor to outdoor tasks requires significant adaptations in sensory and higher-order integration centers of the brain.
The mushroom bodies integrate olfactory, visual, gustatory and mechanosensory information. Furthermore, they play important roles in learning and memory processes. It is therefore not surprising that the mushroom bodies, in particular their main input region, the calyx, undergo volumetric neuronal plasticity. Similar to behavioral maturation, plastic changes of the mushroom bodies are associated with age, but are also to be affected by modulating factors such as task and experience.
In my thesis, I analyzed in detail the neuronal processes underlying volumetric plasticity in the mushroom body. Immunohistochemical labeling of synaptic proteins combined with quantitative 3D confocal imaging revealed that the volume increase of the mushroom body calyx is largely caused by the growth of the Kenyon cell dendritic network. This outgrowth is accompanied by changes in the synaptic architecture of the mushroom body calyx, which is organized in a distinct pattern of synaptic complexes, so called microglomeruli. During the first week of natural adult maturation microglomeruli remain constant in total number. With subsequent behavioral transition from indoor duties to foraging, microglomeruli are pruned while the Kenyon cell dendritic network is still growing. As a result of these processes, the mushroom body calyx neuropil volume enlarges while the total number of microgloumeruli becomes reduced in foragers compared to indoor workers. In the visual subcompartments (calyx collar) this process is induced by visual sensory stimuli as the beginning of pruning correlates with the time window when workers start their first orientation flights. The high level of analysis of cellular and subcellular process underlying structural plasticity of the mushroom body calyx during natural maturation will serve as a framework for future investigations of behavioral plasticity in the honeybee.
The transition to foraging is not purely age-dependent, but gets modulated, for example, by the presence of foragers. Ethyl oleate, a primer pheromone that is present only in foragers, was shown to delay the onset of foraging in nurse bees. Using artificial application of additional ethyl oleate in triple cohort colonies, I tested whether it directly affects adult neuronal plasticity in the visual input region of the mushroom body calyx. As the pheromonal treatment failed to induce a clear behavioral phenotype (delayed onset of foraging) it was not possible to show a direct link between the exposure to additional ethyl oleate and neuronal plasticity in mushroom body calyx. However, the general results on synaptic maturation confirmed my data of natural maturation processes in the mushroom body calyx.
Given the result that dendritic plasticity is a major contributor to neuronal plasticity in the mushroom body calyx associated with division of labor, the question arose which proteins could be involved in mediating these effects. Calcium/calmodulin-dependent protein kinase II (CaMKII) especially in mammals, but also in insects (Drosophila, Cockroach), was shown to be involved in facilitating learning and memory processes like long-term synaptic potentiation. In addition to presynaptic effects, the protein was also revealed to directly interact with cytoskeleton elements in the postsynapse. It therefore is a likely candidate to mediate structural synaptic plasticity. As part of my thesis, the presence and distribution of CaMKII was analyzed, and the results showed that the protein is highly concentrated in a distinct subpopulation of the mushroom body intrinsic neurons, the noncompact Kenyon cells. The dendritic network of this population arborizes in two calyx subregions: one receiving mainly olfactory input – the lip – and the collar receiving visual input. This distribution pattern did not change with age or task. The high concentration of CaMKII in dendritic spines and its overlap with f-actin indicates that CaMKII could be a key player inducing structural neuronal plasticity associated with learning and memory formation and/or behavioral transitions related to division of labor. Interestingly CaMKII immunoreactivity was absent in the basal ring, another subregion of the mushroom body calyx formed almost exclusively by the inner compact Kenyon cells and known to receive combined visual and olfactory input. This indicates differences of this mushroom body subregion regarding the molecular mechanisms controlling plastic changes in corresponding Kenyon cells.
How is timing of behavioral and neuronal plasticity regulated? The primer pheromone ethyl oleate was found in high concentrations on foragers and was shown to influence behavioral maturation by delaying the onset of foraging when artificially applied in elevated concentrations. But how is ethyl oleate transferred and how does it shift the work force distribution between indoor and outdoor tasks? Previous work showed that ethyl oleate concentrations are highest in the honeycrop of foragers and suggested that it is transferred and communicated inside the colony via trophallaxis. The results of this thesis however clearly show, that ethyl oleate was not present inside the honey crop or the regurgitate, but rather in the surrounding tissue of the honey crop. As additionally the second highest concentration of ethyl oleate was measured on the surface of the cuticle of forgers, trophallaxis was ruled out as a mode of transmission. Neurophysiological measurements at the level of the antennae (electroantennogram recordings) and the first olfactory neuropil (calcium imaging of activity in the antennal lobe) revealed that the primer pheromone ethyl oleate is received and processed as an olfactory stimulus. Appetitive olfactory conditioning using the proboscis extension response as a behavioral paradigm showed that ethyl oleate can be associated with a sugar reward. This indicates that workers are able to perceive, learn and memorize the presence of this pheromone. As ethyl oleate had to be presented by a heated stimulation device at close range, it can be concluded that this primer pheromone acts via close range/contact chemoreception through the olfactory system. This is also supported by previous behavioral observations.
Taken together, the findings presented in this thesis revealed structural changes in the synaptic architecture of the mushroom body calyx associated with division of labor. For the primer pheromone ethyl oleate, which modulates the transition from nursing to foraging, the results clearly showed that it is received via the olfactory system and presumably acts via this pathway. However, manipulation experiments did not indicate a direct effect of ethyl oleate on synaptic plasticity. At the molecular level, CaMKII is a prime candidate to mediate structural synaptic plasticity in the mushroom body calyx. Future combined structural and functional experiments are needed to finally link the activity of primer pheromones like ethyl oleate to the molecular pathways mediating behavioral and synaptic plasticity associated with division of labor in Apis mellifera. The here identified underlying processes will serve as excellent models for a general understanding of fundamental mechanisms promoting behavioral plasticity.
Anxiety is an affective state characterized by a sustained, long-lasting defensive response, induced by unpredictable, diffuse threat. In comparison, fear is a phasic response to predictable threat. Fear can be experimentally modeled with the help of cue conditioning. Context conditioning, in which the context serves as the best predictor of a threat due to the absence of any conditioned cues, is seen as an operationalization of sustained anxiety.
This thesis used a differential context conditioning paradigm to examine sustained attention processes in a threat context compared to a safety context for the first time. In three studies, the attention mechanisms during the processing of contextual anxiety were examined by measuring heart rate responses and steady-state-visually evoked potentials (ssVEPs). An additional focus was set on the processing of social cues (i.e. faces) and the influence of contextual information on these cues. In a last step, the correlates of sustained anxiety were compared to evoked responses by phasic fear, which was realized in a previously established paradigm combining predictable and unpredictable threat.
In the first study, a contextual stimulus was associated with an aversive loud noise, while a second context remained unpaired. This conditioning paradigm created an anxiety context (CTX+) and a safety context (CTX-). After acquisition, a social agent vs. an object was presented as a distractor in both contexts. Heart rate and cortical responses, with ssVEPs by using frequency tagging, to the contexts and the distractors were assessed. Results revealed enhanced ssVEP amplitudes for the CTX+ compared to the CTX− during acquisition and during presentation of distractor stimuli. Additionally, the heart rate was accelerated in the acquisition phase, followed by a heart rate deceleration as a psychophysiological marker of contextual anxiety.
Study 2 used the same context conditioning paradigm as Study 1. In contrast to the first study, persons with different emotional facial expressions were presented in the anxiety and safety contexts in order to compare the differential processing of these cues within periods of threat and safety. A similar anxiety response was found in the second study, although only participants who
Abstract
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were aware of the contingency between contexts and aversive event showed a sensory amplification of the threat context, indicated by heart rate response and ssVEP activation. All faces irrespective of their emotional expression received increased attentional resources when presented within the anxiety context, which suggests a general hypervigilance in anxiety contexts.
In the third study, the differentiation of predictable and unpredictable threat as an operationalization of fear and anxiety was examined on a cortical and physiological level. In the predictable condition, a social cue was paired with an aversive event, while in the unpredictable condition the aversive event remained unpaired with the respective cue. A fear response to the predictable cue was found, indicated by increased oscillatory response and accelerated heart rate. Both predictable and unpredictable threat yielded increased ssVEP amplitudes evoked by the context stimuli, while the response in the unpredictable context showed longer-lasting ssVEP activation to the threat context.
To sum up, all three studies endorsed anxiety as a long-lasting defensive response. Due to the unpredictability of the aversive events, the individuals reacted with hypervigilance in the anxiety context, reflected in a facilitated processing of sensory information and an orienting response. This hypervigilance had an impact on the processing of novel cues, which appeared in the anxiety context. Considering the compared stimuli categories, the stimuli perceived in a state of anxiety received increased attentional resources, irrespective of the emotional arousal conveyed by the facial expression. Both predictable and unpredictable threat elicited sensory amplification of the contexts, while the response in the unpredictable context showed longer-lasting sensory facilitation of the threat context.
Brain-computer interfaces (BCIs) could provide a muscle-independent communication channel to persons with severe paralysis by translating brain activity into device commands. As a means of communication, in particular BCIs based on event-related potentials (ERPs) as control signal have been researched. Most of these BCIs rely on visual stimulation and have been investigated with healthy participants in controlled laboratory environments. In proof-of-principle studies targeted end users gained control over BCI systems; however, these systems are not yet established as an assistive technology for persons who would most benefit from them. The main aim of this thesis is to advance the usability of ERP-BCIs for target users. To this end, five studies with BCIs have been conducted that enabled users to communicate by focusing their attention on external stimuli.
Two studies were conducted in order to demonstrate the advantages and to further improve the practical application of visual BCIs. In the first study, mental workload was experimentally manipulated during prolonged BCI operation. The study showed the robustness of the visual ERP-BCI since users maintained a satisfactory level of control despite constant distraction in the form of background noise. Moreover, neurophysiological markers that could potentially serve as indicators of high mental workload or fatigue were revealed. This is a first step towards future applications in which the BCI could adapt to the mental state of the user (e.g. pauses if high mental workload is detected to prevent false selections). In the second study, a head-mounted display (HMD), which assures that stimuli are presented in the field of view of the user, was evaluated. High accuracies and information transfer rates, similar to a conventional display, were achieved by healthy participants during a spelling task. Furthermore, a person in the locked-in state (LIS) gained control over the BCI using the HMD. The HMD might be particularly suited for initial communication attempts with persons in the LIS in situations, where mounting a conventional monitor is difficult or not feasible.
Visual ERP-BCIs could prove valuable for persons with residual control over eye muscles and sufficient vision. However, since a substantial number of target users have limited control over eye movements and/or visual impairments, BCIs based on non-visual modalities are required. Therefore, a main aspect of this thesis was to improve an auditory paradigm that should enable motor impaired users to spell by focusing attention on different tones. The two conducted studies revealed that healthy participants were able to achieve high spelling performance with the BCI already in the first session and stress the importance of the choice of the stimulus material. The employed natural tones resulted in an increase in performance compared to a previous study that used artificial tones as stimuli. Furthermore, three out of five users with a varying degree of motor impairments could gain control over the system within the five conducted sessions. Their performance increased significantly from the first to the fifth session - an effect not previously observed for visual ERP-BCIs. Hence, training is particularly important when testing auditory multiclass BCIs with potential users.
A prerequisite for user satisfaction is that the BCI technology matches user requirements. In this context, it is important to compare BCIs with already established assistive technology. Thus, the fifth study of this dissertation evaluated gaze dependent methods (EOG, eye tracking) as possible control signals for assistive technology and a binary auditory BCI with a person in the locked-in state. The study participant gained control over all tested systems and rated the ease of use of the BCI as the highest among the tested alternatives, but also rated it as the most tiring due to the high amount of attention that was needed for a simple selection. Further efforts are necessary to simplify operation of the BCI.
The involvement of end users in all steps of the design and development process of BCIs will increase the likelihood that they can eventually be used as assistive technology in daily life. The work presented in this thesis is a substantial contribution towards the goal of re-enabling communication to users who cannot rely on motor activity to convey their thoughts.