30 episodes

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Graduate School of Systemic Neurosciences - Digitale Hochschulschriften der LMU Ludwig-Maximilians-Universität München

    • Education

Die Universitätsbibliothek (UB) verfügt über ein umfangreiches Archiv an elektronischen Medien, das von Volltextsammlungen über Zeitungsarchive, Wörterbücher und Enzyklopädien bis hin zu ausführlichen Bibliographien und mehr als 1000 Datenbanken reicht. Auf iTunes U stellt die UB unter anderem eine Auswahl an Dissertationen der Doktorandinnen und Doktoranden an der LMU bereit.

    Information integration and neural plasticity in sensory processing investigated at the levels of single neurons, networks, and perception

    Information integration and neural plasticity in sensory processing investigated at the levels of single neurons, networks, and perception

    In this doctoral thesis, several aspects of information integration and learning in neural systems are investigated at the levels of single neurons, networks, and perception.
    In the first study presented here, we asked the question of how contextual, multiplicative interactions can be mediated in single neurons by the physiological mechanisms available in the brain. Multiplicative interactions are omnipresent in the nervous system and although a wealth of possible mechanisms were proposed over the last decades, the physiological origin of multiplicative interactions in the brain remains an open question. We investigated permissive gating as a possible multiplication mechanism. We proposed an integrate-and-fire model neuron that incorporates a permissive gating mechanism and investigated the model analytically and numerically due to its abilities to realize multiplication between two input streams. The applied gating mechanism realizes multiplicative interactions of firing rates on a wide range of parameters and thus provides a feasible model for the realization of multiplicative interactions on the single neuron level.
    In the second study we asked the question of how gaze-invariant representations of visual space can develop in a self-organizing network that incorporates the gating model neuron presented in the first study. To achieve a stable representation of our visual environment our brain needs to transform the representation of visual stimuli from a retina-centered coordinate system to a frame of reference that is independent of changes in gaze direction. In the network presented here, receptive fields and gain fields organized in overlayed topographic maps that reflected the spatio-temporal statistics of the training input stream. Topographic maps supported a gaze-invariant representation in an output layer when the network was trained with natural input statistics. Our results show that gaze-invariant representations of visual space can be learned in an unsupervised way by a biologically plausible network based on the spatio-temporal statistics of visual stimulation and eye position signals under natural viewing conditions.
    In the third study we investigated psychophysically the effect of a three day meditative Zen retreat on tactile abilities of the finger tips. Here, meditators strongly altered the statistics of their attentional focus by focussing sustained attention on their right index finger for hours. Our data shows that sustained sensory focussing on a particular body part, here the right index finger, significantly affects tactile acuity indicating that merely changing the statistics of the attentional focus without external stimulation or training can improve tactile acuity.
    In the view of activity-dependent plasticity that is outlined in this thesis, the main driving force for development and alterations of neural representations is nothing more than neural activity itself. Patterns of neural activity shape our brains during development and significant changes in the patterns of neural activity inevitably change mature neural representations. At the same time, the patterns of neural activity are formed by environmental sensory inputs as well as by contextual, multiplicative inputs like gaze-direction or by internally generated signals like the attentional focus. In this way, our environments as well as our inner mental states shape our neural representations and our perception at any time.

    Motor variability as a characteristic of the control of reaching movements

    Motor variability as a characteristic of the control of reaching movements

    Antidepressant activated biochemical pathways and biomarker candidates

    Antidepressant activated biochemical pathways and biomarker candidates

    Most of the commonly used antidepressants block monoamine reuptake transporters to enhance serotonergic or noradrenergic neurotransmission. Effects besides or downstream of increased monoaminergic neurotransmission are poorly understood and yet presumably important for the drugs’ mode of action. In my PhD thesis I employed proteomics and metabolomics technologies combined with in silico analyses and identified cellular pathways affected by antidepressant drug treatment. DBA/2 mice were treated with paroxetine as a representative Selective Serotonin Reuptake Inhibitor (SSRI). Hippocampal protein levels were compared between chronic paroxetine- and vehicle-treated animals using in vivo 15N metabolic labeling combined with mass spectrometry. I also studied chronic changes in the hippocampus using unbiased metabolite profiling and the time course of metabolic changes with the help of a targeted polar metabolomics profiling platform. I identified profound alterations related to hippocampal energy metabolism. Glycolytic metabolite levels acutely increased while Krebs cycle metabolite levels decreased upon chronic treatment. Changes in energy metabolism were influenced by altered glycogen metabolism rather than by altered glycolytic or Krebs cycle enzyme levels. Increased energy levels were reflected by an increased ATP/ADP ratio and by increased ratios of high-to-low energy purines and pyrimidines. Paralleling the shift towards aerobic glycolysis upon paroxetine treatment I identified decreased levels of Krebs cycle and oxidative phosphorylation enzyme levels upon the antidepressant-like 15N isotope effect in high-anxiety behavior mice. In the course of my analyses I also identified GABA, galactose-6-phosphate and leucine as biomarker candidates for the assessment of chronic paroxetine treatment effects in the periphery and myo-inositol as biomarker candidate for an early assessment of chronic treatment effects. The identified antidepressant drug treatment affected molecular pathways and novel SSRI modes of action warrant consideration in antidepressant drug development efforts.

    Spatial and temporal resolution of bat sonar

    Spatial and temporal resolution of bat sonar

    Making eyes with others

    Making eyes with others

    Components of aging

    Components of aging

    Age-related cognitive decline has been linked to a reduction in attentional resources that are assumed to result from alterations in the aging brain. A core ability that is subject to age-related decline is visual attention, which enables individuals to select the most important information for conscious processing and action. However, visual attention is considered a conglomerate of various functions and the specific components underlying age differences in performance remain little understood. The present PhD project aimed at dissociating age effects on several (sub-) components that concur in visual attention tasks within a neurocognitive approach. Established and theoretically grounded psychological paradigms that allow separating various attentional components were combined with event-related potentials (ERPs), which provide a temporally fine-graded dissociation of cognitive processes involved in a task.
    1st Project
    The first project was designed to determine the origin(s) of age-related decline in visual search, a key paradigm of attention research. To pursue this goal on a micro-level, response time measures in a compound-search task, in which the target-defining feature of a pop-out target (color/shape) was dissociated from the response-defining feature (orientation), were coupled with lateralized ERPs. Several ERP components tracked the timing of processing stages involved in this task, these being (1) allocation of attention to the target, marked by the posterior-contralateral negativity (PCN), (2) target analyses in vSTM, marked by the sustained posterior-contralateral negativity (SPCN), (3) response selection, marked by the stimulus-locked lateralized readiness potential (LRP) and (4) response execution, marked by the response-locked LRP. Slowed response times (RT) in older participants were associated with age differences in all analyzed ERPs, indicating that behavioural slowing accrues across multiple stages within the information processing stream. Furthermore,
    v
    behavioral data and ERPs were analyzed with respect to age and carry-over effects from one trial to the next. The intertrial analyses revealed relatively automatic processes – such as dimension weighting facilitating the early stage of visual selection, and response weighting facilitating the late stage of response execution – to be preserved in older age. By contrast, more controlled processes – such as the flexible stimulus-response (S-R) (re-) mapping across trials on the intermediate stages of response selection - were particularly affected by aging. This indicates that besides general slowing, specific age decrements in executively controlled processes contribute to age-related decline in visual search.
    2nd Project
    The second project explored neural markers of individual and age differences in attention parameters formally integrated in Bundesen’s computational Theory of Visual Attention (TVA). According to the model, two parameters of general visual attention capacity, perceptual processing speed C and visual short-term memory (vSTM) storage capacity K are defined and can be modeled mathematically independently for a particular individual. More recently, the neural interpretation of the model (NTVA) suggested that the two functions (at least partly) rely on distinct brain mechanisms. To test this assumption in an empirical approach, individual TVA-based estimates were derived in a standard TVA whole report task, and ERPs of the same participants were recorded in an adapted EEG-compatible version of the task. In the first study of the second project, we explored neurophysiological markers of interindividual differences in the two functions in younger participants. The results revealed distinct ERP correlates to be related to the parameters: Individuals with higher compared to lower processing speed C had significantly smaller posterior N1

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