@phdthesis{Plichta2009,
  author    = {Plichta, Michael M.},
  title     = {Neural correlates of delay discounting: Effects of dopamine bioavailability and implications for attention-deficit/hyperactivity disorder (ADHD)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-35953},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Humans and other animals share choice preference for smaller-but-sooner over later-but-larger rewards, indicating that the subjective value of a reward is discounted as a function of time. This phenomenon referred to as delay discounting (DD), represents one facet of impulsivity which is inherently connected with reward processing and, within a certain range, adaptive. Maladaptive levels, however, can lead to suboptimal decision-making and represent important characteristics of psychopathologies such as attention-deficit/hyperactivity disorder (ADHD). In line with a proposed influence of dysregulated dopamine (DA) levels on impulsivity, neural structures involved in DD (the ventral-striatum [VS]; orbitofrontal cortex [OFC]) are highly innervated by dopaminergic neurons. However, studies explicitly testing the triadic interplay of dopaminergic neurotransmission, impulsivity and brain activation during intertemporal choice are missing. Therefore, the first study of the thesis examined the effect of different DA-bioavailability levels, indicated by a genetic polymorphism (Val158Met) in the gene of the catechol-O-methyltransferase, on the association of delay discounting and OFC activation. OFC response to monetary rewards that varied by delay-to-delivery was recorded with functional near-infrared spectroscopy (fNIRS) in a sample of 49 healthy human subjects. The results suggest a DA-related enhancement in OFC function from low (low DA level) to partial (intermediate DA level) and full (high DA level) reward delay sensitivity. Furthermore, DA-bioavailability was shown to moderate the association of neural reward delay sensitivity and impulsivity: OFC reward delay sensitivity was strongly correlated with impulsivity at intermediate DA-levels, but not at low or high DA-levels where impulsivity was related to delay-independent OFC amplitudes. It is concluded that DA-level should be considered as a crucial factor whenever impulsivity-related brain activation, in particular to reward delay, is examined in healthy subjects. Dysfunctional reward processing, accompanied by a limited ability to tolerate reward delays (delay aversion), has been proposed as an important feature in ADHD putatively caused by striatal hypo-dopaminergia. Therefore, the aim of the second study of this thesis was to examine subcortical processing of reward delays and to test for neural indicators of a negative emotional response to delay periods. Using functional magnetic resonance imaging (fMRI), brain activation in adult patients with ADHD (n=14) and healthy control subjects (n=12) was recorded during the processing of immediate and delayed rewards. Compared with healthy control subjects, hyporesponsiveness of the VS reward system was evident in patients with ADHD for both immediate and delayed rewards. In contrast, delayed rewards evoked hyperactivation in the dorsal caudate nucleus and the amygdala of ADHD patients, corroborating the central predictions of the delay aversion hypothesis. In combination both studies support the conception of a close link between delay discounting, brain activation and dopaminergic neurotransmission. The results implicate that studies on neural correlates of DD have to account for the DA-bioavailability level and for a negative emotional response to reward delays.},
  subject      = {Impulsivit{\"a}t},
  language  = {en}
}
@phdthesis{Liedtke2007,
  author    = {Liedtke, Daniel},
  title     = {Functional divergence of Midkine growth factors : Non-redundant roles during neural crest induction, brain patterning and somitogenesis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25707},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Neural crest cells and sensory neurons are two prominent cell populations which are induced at the border between neural and non-neural ectoderm during early vertebrate development. The neural crest cells are multipotent and highly migratory precursors that give rise to face cartilage, peripheral neurons, glia cells, pigment cells and many other cell types unique to vertebrates. Sensory neurons are located dorsally in the neural tube and are essential for sensing and converting environmental stimuli into electrical motor reflexes. In my PhD thesis, I obtained novel insights into the complex processes of cell induction at the neural plate border by investigating the regulation and function of mdkb in zebrafish. First, it was possible to demonstrate that mdkb expression is spatiotemporally correlated with the induction of neural crest cells and primary sensory neurons at the neural plate border. Second, it became evident that the expression of mdkb is activated by known neural crest cell inducing signals, like Wnts, FGFs and RA, but that it is independent of Delta-Notch signals essential for lateral inhibition. Knockdown experiments showed that mdkb function is necessary for induction of neural crest cells and sensory neurons at the neural plate border, probably through determination of a common pool of progenitor cells during gastrulation. The present study also used the advantages of the zebrafish model system to investigate the in vivo function of all midkine gene family members during early brain development. In contrast to the situation in mouse, all three zebrafish genes show distinct expression patterns throughout CNS development. mdka, mdkb and ptn expression is detected in mostly non-overlapping patterns during embryonic brain development in the telencephalon, the mid-hindbrain boundary and the rhombencephalon. The possibility of simultaneously knocking down two or even three mRNAs by injection of morpholino mixtures allowed the investigation of functional redundancy of midkine factors during brain formation. Knockdown of Midkine proteins revealed characteristic defects in brain patterning indicating their association with the establishment of prominent signaling centers such as the mid-hindbrain boundary and rhombomere 4. Interestingly, combined knockdown of mdka, mdkb and ptn or single knockdown of ptn alone prevented correct formation of somites, either by interfering with the shifting of the somite maturation front or interferance with cell adhesion in the PSM. Thus, Ptn was identified as a novel secreted regulator of segmentation in zebrafish.},
  subject      = {Zebrab{\"a}rbling},
  language  = {en}
}
@phdthesis{Dresler2011,
  author    = {Dresler, Thomas},
  title     = {Die neuronale Verarbeitung emotionaler Reize bei Patienten mit Panikst{\"o}rung - eine Betrachtung der neuroanatomischen Hypothese},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64932},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Hintergrund: Die Panikst{\"o}rung ist eine die Lebensqualit{\"a}t beeintr{\"a}chtigende psychische St{\"o}rung, die unbehandelt einen chronischen Verlauf zeigt, jedoch sowohl durch Psychotherapie als auch Psychopharmakotherapie erfolgreich behandelt werden kann. Die der Panikst{\"o}rung zugrundeliegenden neuronalen Schaltkreise werden in der von Gorman et al. (1989, 2000) ver{\"o}ffentlichten neuroanatomischen Hypothese beschrieben. In der stark an der Tierforschung angelehnten revidierten Version (2000) wird die Amygdala als Zentrum eines komplexen Furchtnetzwerks angesehen, deren Aktivit{\"a}t durch h{\"o}here kortikale Areale im pr{\"a}frontalen Kortex moduliert wird. Trotz der Popularit{\"a}t der Hypothese sind deren Annahmen bislang kaum explizit {\"u}berpr{\"u}ft worden. Ziel: Ziel der Untersuchung war es, die neuronale Verarbeitung emotionaler Reize in empirischen Experimenten genauer zu untersuchen, da die Datenlage in diesem Bereich noch gering und inkonsistent ist und Replikationsstudien fehlen. Außerdem sollte ein {\"U}berblick {\"u}ber die bereits ver{\"o}ffentlichten empirischen Studien gegeben werden, welche mit bildgebenden Verfahren Aussagen {\"u}ber die Beteiligung bestimmter neuronaler Strukturen bei der Panikst{\"o}rung erlauben. Methoden: An den Standorten W{\"u}rzburg und Hamburg wurden Patienten mit Panikst{\"o}rung (n = 18/20) und gesunde Kontrollen (n = 27/23) mit zwei Paradigmen zur Verarbeitung emotionaler Reize (emotionaler Stroop-Test und Gesichterverarbeitung) mit der funktionellen Magnetresonanztomographie untersucht. Hierbei sollten insbesondere die in der neuroanatomischen Hypothese wichtigen Strukturen Amygdala und pr{\"a}frontaler Kortex betrachtet werden. Bildgebende Studien, die Patienten mit Panikst{\"o}rung untersuchten, wurden {\"u}ber eine Literaturrecherche ermittelt, in Untergruppen von Studien eingeteilt und bewertet. Ergebnisse: In beiden untersuchten Stichproben zeigten die Patienten im Vergleich zu den Kontrollen auf Reaktionszeitebene einen signifikanten emotionalen Stroop-Effekt mit verl{\"a}ngerten Antwortlatenzen f{\"u}r panikrelevante W{\"o}rter. In den funktionellen Daten zeigten sich keine Unterschiede in der Amygdalaaktivierung, jedoch zeigten die Patienten f{\"u}r den Kontrast ‚panikrelevante vs. neutrale W{\"o}rter' im Gruppenvergleich eine erh{\"o}hte Aktivierung in pr{\"a}frontalen Arealen. Bei der Verarbeitung emotionaler Gesichter gab es kaum Unterschiede zwischen den Gruppen, {\"a}ngstliche Gesichter l{\"o}sten im Vergleich zu neutralen Gesichtern keine erh{\"o}hte Amygdalaaktivierung aus. Hinweise auf eine generelle Hypofrontalit{\"a}t ließen sich bei den Patienten - zumindest bei der Verarbeitung emotionaler Reize - in den angewandten Paradigmen nicht finden. Schlussfolgerung: Die Ergebnisse der experimentellen Untersuchung und des Literatur{\"u}berblicks zeigen, dass - trotz durchaus mit der neuroanatomischen Hypothese in Einklang stehender Befunde - Inkonsistenzen zu finden sind, die mit der aktuellen Hypothese nicht erkl{\"a}rt werden k{\"o}nnen. Die Ergebnisse der vorliegenden Untersuchung im emotionalen Stroop-Test konnten bisher gefundene pr{\"a}frontale Aktivierungsmuster replizieren, f{\"u}r die Amygdala gilt das nicht. Eine Erweiterung der Hypothese durch die Ber{\"u}cksichtigung neuer Aspekte k{\"o}nnte helfen, diese Befunde besser zu erkl{\"a}ren und zu einem umfassenderen Bild der neuronalen Grundlagen der St{\"o}rung beitragen. Modifikationen werden vorgeschlagen, die der Weiterentwicklung der Hypothese dienen k{\"o}nnten und bei der Planung zuk{\"u}nftiger Studien ber{\"u}cksichtigt werden sollten. Die vermutete prominente Rolle der Amygdala bei der Panikst{\"o}rung ist nach wie vor nicht hinreichend untersucht und der modulierende Einfluss pr{\"a}frontaler Strukturen sollte zuk{\"u}nftig insbesondere im direkten Zusammenspiel mit der Amygdala, z. B. im Rahmen psychotherapeutischer Interventionen, genauer analysiert werden.},
  subject      = {Paniksyndrom},
  language  = {de}
}