An emotion-induced enhancement of episodic memory formation seems to have costs and benefits. Multiple lines of evidence implicate the amygdala and ß-adrenergic mechanisms in emotion-induced memory enhancements at long retention intervals. Therefore, one might predict that similar mechanisms are also involved in emotion-induced memory enhancements – and impairments – at short retention intervals. Chapter 2 introduces to a series of psychological, neuropsychological and pharmacological experiments that test this prediction and involve a retrograde amnesic effect in response to emotional oddballs. The role of amygdala- and ß- adrenergic-dependent mechanisms in emotion-induced retrograde amnesia is probed by testing a rare amygdala-lesioned patient with Urbach-Wiethe disease and by conducting a pharmacological challenge using the ß-adrenergic receptor antagonist propranolol. In Chapter 3, the experimental focus is widened to retrograde and anterograde episodic memory changes in response to emotional oddballs. Emerging evidence indicates dissociable contributions of arousal and valence to emotion-induced memory enhancements. This raises the question whether a similar dissociation might underlie the design that the brain uses to organize forgetting and remembering by emotion. To prove this question, emotional valence and arousal are manipulated by testing positive and negative oddballs relative to neutral oddballs under experimental conditions of low arousal (established by ß-adrenergic blockade with propranolol) versus high arousal (established by NE re-uptake inhibition with reboxetine). In Chapter 4, based on the data accumulated in the previous chapters, a neurocircuitry model of emotion-induced forgetting and remembering as a function of PFC-hippocampal and amygdala-hippocampal interactions during emotional memory encoding is developed. If emotion-induced forgetting and remembering both require integrity of the BLA, it should be abolished in Urbach-Wiethe patients with a disease emphasis on this subregion as confirmed with cytoarchitectonic maximum probability maps of the amygdala. In Chapter 5, this hypothesis is tested in a study of two monozygotic female twins with Urbach-Wiethe disease. Cytoarchitectonic maximum probability maps not only allow to accurately identify structural brain abnormalities, but may also be useful as an atlas for the accurate anatomical analysis of functional imaging data. The technical feasibility of this approach is tested in Chapter 6, which presents a quantitative analysis of in vivo neuroreceptor positron emission tomography (PET) data based on such maps. In the following two chapters, the focus shifts to the potential significance of emotioninduced amnesia in pathological conditions such as borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD). Current theories of BPD emphasize the disruptive potential of dysregulated negative emotion on cognitive functioning. These disruptive effects could result from amygdala hyper-responsiveness to negative emotion. Therefore, Chapter 7 presents a study of sixteen female BPD patients tested on the behavioral indices of emotion-induced forgetting and remembering established in matched controls. Preliminary evidence from human fMRI studies suggests synergistic effects of NE and cortisol (CORT) in amplifying amygdala responses during emotional encoding. NE-CORT interactions could thus determine the magnitude of emotioninduced amnesia, which – when expressed in extreme forms – constitutes a powerful predictive risk factor for PTSD. In an attempt to experimentally model the neurochemical mechanism precipitating amnesia by emotional trauma, Chapter 8 presents a pharmacological study, where the emotion-induced amnesic potential of elevated CORT levels is tested in the presence or absence of elevated NE levels. Finally, the results of the previous chapters are integrated in the concluding Chapter 9.weiterlesen