@phdthesis{Kopf2018,
  author    = {Kopf, Juliane},
  title     = {Emotion processing and working memory deficits in Bipolar Disorder: interactions and changes from acute to remitted state},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97752},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {BD is a severe and highly prevalent psychiatric illness characterized by oscillating mood episodes, where patients express either depressed mood, anhedonia, decreased activation along with concentration difficulties and sleep disturbances, or elevated mood with hyperactivity and loss of inhibitions. Between mood episodes, patients return to a relatively normal state of functioning without mood symptoms. Previous research on underlying neuronal mechanisms has led to a model of neuronal dysfunction in BD which states that BD arises from disruption in early development within brain networks that modulate emotional behavior. These abnormalities in the structure and function of key emotional control networks then lead to decreased connectivity among ventral prefrontal networks and limbic brain regions. This in turn creates a loss of emotional homeostasis, putting bipolar patients at risk for developing extreme mood states and switching among mood states. Two core components for BD have been identified, a hyperactive emotion processing system and a hypoactive cognitive functions system. It is controversial whether these deficits are still detectable in euthymia, so it is unclear if hyper- and hypoactivations represent state or trait-like characteristics. The aim of this study was to research both core components of BD with a paradigm eliciting differential activations in both cognitive and emotion processing networks. For this, an emotional word working memory paradigm was constructed to test for differences between manic, depressive, and remitted patients as well as a healthy control group. Differences were assessed in behavior, brain activation (as a correlate for the hypoactive cognitive functions system), measured with near-infrared spectroscopy (fNIRS), and electrophysiological changes in the late positive potential (as a correlate for the hyperactive emotion processing system), an event-related potential (ERP) measured with electroencephalography. 47 patients in the acutely ill phase and 45 healthy controls were measured. Of the 47 patients, 18 returned to the clinic for a second testing while in remission for at least 3 months. Acutely ill patients were classified into 4 groups according to their disorder status: a mildly depressed group, a depressed group, a manic group, and a mixed group along DSM-IV criteria. Analyses were calculated for 3 load conditions (1-back, 2-back and 3-back) and 3 valence conditions (negative, neutral, positive) for behavioral measures reaction time and omission errors, for brain activation and event related potential changes. Results indicate that ill patients differed from controls in their behavioral performance, but the difference in performance was modulated by the mood state they were in. Depressed patients showed the most severe differences in all behavioral measures, while manic and mixed patients differed from controls only upon different valence conditions. Brain activation changes were most pronounced in mildly depressed and manic patients, depressed patients and mixed patients did not differ as much from controls. ERP changes showed a significant difference only between mixed patients and controls, where mixed patients had an overall much higher ERP amplitude. When remitted patients were compared to controls, no differences in behavior, brain activation or ERP amplitude could be found. However, the same was true for differences in patients between acutely ill and remitted state. When looking at the overall data, the following conclusion can be drawn: assuming that the brain activation seen in the prefrontal cortex is part of the dorsal cognitive system, then this is the predominantly disturbed system in depressed patients who show only small changes in the ERP. In contrast, the predominantly disturbed system in manic and mixed patients is the ventral emotion processing system, which can be seen in a hyper-activation of ERP related neural correlates in mixed and hypo-activated neural correlates of the LPP in manic patients. When patients are remitted, the cognitive system regains temporary stability, and can be compared to that of healthy controls, while the emotion processing system remains dysfunctional and underlies still detectable performance deficits.},
  subject      = {Manisch-depressive Krankheit},
  language  = {en}
}
@phdthesis{Biehl2014,
  author    = {Biehl, Stefanie},
  title     = {The Impact of Adult Attention Deficit/ Hyperactivity Disorder, Methylphenidate, and the COMT Val158Met Polymorphism on Selective Attention and Working Memory},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-100959},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Theories of attention deficit hyperactivity disorder (ADHD) aetiology have placed a focus on impaired behavioural inhibition presumably leading to executive function (EF) deficits. Neuroimaging studies report neurophysiological findings consistent with these hypothesised impairments, and investigations of functional brain activation from a network perspective report hypoactivation in the frontoparietal network as well as hyperactivation in the dorsal attention network. Studies investigating the acute effects of stimulant medication on EF show an improvement on behavioural EF measures including working memory. In addition, methylphenidate (MPH) was shown to up-regulate the task-positive/ frontoparietal network in children and adolescents with ADHD. So far, there are only few studies investigating the impact of ADHD on behavioural and neurophysiological EF measures as well as the effect of several weeks of stimulant medication in adult patients. The importance of the catechol-O-methyltransferase (COMT) enzyme for subcortical and cortical dopaminergic and noradrenergic functioning furthermore led to studies investigating a potential interactive impact of COMT genotype and ADHD on neuropsychological functioning, with a particular focus on working memory. The results of these studies were very heterogeneous. In addition, as none of the studies compared the results of ADHD patients to those of a healthy control group, possible differential effects of COMT in patients and healthy controls could not be examined. The aim of this dissertation was to investigate selective attention properties of the central executive component during a working memory task and to transfer this task to fMRI. A third study then aimed to investigate the effects of adult ADHD (aADHD), MPH, and COMT genotype on working memory with a particular focus on activation of the task-positive network during the analysis of the fMRI data. The first study (EEG) could replicate and extend the results from previous research. This study could furthermore connect the overall activation in frontal areas to suppression efficiency in posterior visual areas as well as establish the impact of hyperactive/ impulsive ADHD symptoms on task performance. The second study (fMRI) allowed the successful transfer of the paradigm to fMRI, and the further replication and extension of previous findings. In addition, this study showed the sensitivity of the task to the effects of the COMT genotype. The third study (fMRI) was one of the first studies that exploratorily investigated the effects COMT in a sample of aADHD patients and a comparable healthy control group. This study showed an interactive effect of these two factors on neuropsychological measures as well as on fMRI activation during a classic n-back working memory task. In addition, this task led to more activation in the task-positive network of the aADHD group compared to a healthy control group in the absence of performance differences, pointing towards compensatory activation in the aADHD group. Furthermore, activation in the frontal cortex was increased in patients taking MPH compared to a placebo. The fMRI data from the selective attention task moreover showed decreased activation in the right DLPFC of the patient group, which was associated with reduced suppression efficiency across all participants. The clinical effect of MPH in the third study was visible but did not reach significance, which is probably attributable to a lack of experimental power. The studies in this dissertation could successfully replicate and extend previous findings. A goal for future studies should be the further investigation of the interactive effects of COMT genotype and aADHD on neuropsychological test results and fMRI activation, but also on medication response and adverse effects. In this context, the adaptation of a network perspective during the analysis of fMRI data seems to be the best way to detect existing between-group differences.},
  subject      = {Aufmerksamkeits-Defizit-Syndrom},
  language  = {en}
}