There is a lot of evidence for the impact of acute glucocorticoid treatment on hippocampus-dependent explicit learning and memory (memory for facts and events). But there have been few studies, investigating the effect of glucocorticoids on implicit learning and memory. We conducted three studies with different methodology to investigate the effect of glucocorticoids on different forms of implicit learning. In Study 1, we investigated the effect of cortisol depletion on short-term habituation in 49 healthy subjects. 25 participants received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. Eye blink electromyogram (EMG) responses to 105 dB acoustic startle stimuli were assessed. Effective endogenous cortisol suppression had no effect on short-term habituation of the startle reflex, but startle eye blink responses were significantly increased in the metyrapone group. The latter findings are in line with previous human studies, which have shown that excess cortisol, sufficient to fully occupy central nervous system (CNS) corticosteroid receptors, may reduce startle eye blink. This effect may be mediated by CNS mechanisms controlling cortisol feedback. In Study 2, we investigated delay or trace eyeblink conditioning in a patient group with a relative hypocortisolism (30 patients with fibromyaligia syndrome/FMS) compared to 20 healthy control subjects. Conditioned eyeblink response probability was assessed by EMG. Morning cortisol levels, ratings of depression, anxiety and psychosomatic complaints as well as general symptomatology and psychological distress were assessed. As compared to healthy controls FMS patients showed lower morning cortisol levels, and trace eyeblink conditioning was facilitated whereas delay eyeblink conditioning was reduced. Cortisol measures correlate significantly only with trace eyeblink conditioning. Our results are in line with studies of pharmacologically induced hyper- and hypocortisolism, which affected trace eyeblink conditioning. We suggest that endocrine mechanisms affecting hippocampus-mediated forms of associative learning may play a role in the generation of symptoms in these patients.rnIn Study 3, we investigated the effect of excess cortisol on implicit sequence learning in healthy subjects. Oral cortisol (30 mg) was given to 29 participants, whereas 31 control subjects received placebo. All volunteers performed a 5-choice serial reaction time task (SRTT). The reaction speed of every button-press was determined and difference-scores were calculated as a proof of learning. Compared to the control group, we found a delayed learning in the cortisol group at the very beginning of the task. This study is the first human investigation, indicating impaired implicit memory function after exogenous administration of the stress hormone cortisol. Our findings support a previous neuroimaging study, which suggested that the medial temporal lobe (including the hippocampus) is also active in implicit sequence learning, but our results may also depend on the engagement of other brain structures.
The last decades of stress research have yielded substantial advancements highlighting the importance of the phenomenon for basic psychological functions as well as physical health and well-being. Progress in stress research heavily relies on the availability of suitable and well validated laboratory stressors. Appropriate laboratory stressors need to be able to reliably provoke a response in the relevant parameters and be applicable in different research settings or experimental designs. This thesis focuses on the Cold Pressor Test (CPT) as a stress induction technique. Three published experiments are presented that show how the advantages of the CPT can be used to test stress effects on memory processes and how some of its disadvantages can be met by a simple modification that retains its feasibility and validity. The first experiment applies the CPT in a substantial sample to investigate the consolidation effects of post-learning sympathetic arousal. Stressed participants with high increases in heart rate during the CPT showed enhanced memory performance one day after learning compared to both the warm water control group and low heart rate responders. This finding suggests that beta-adrenergic activation elicited shortly after learning enhances memory consolidation and that the CPT induced heart rate response is a predictor for this effect. Moreover, the CPT proved to be an appropriate stressor to test hypothesis about endogenous adrenergic effects on memory processes. The second experiment addresses known practical limitations of the standard dominant hand CPT protocol. A bilateral feet CPT modification is presented, the elicited neuroendocrine stress response assessed and validated against the standard CPT in a within-subjects design. The bilateral feet CPT elicited a substantial neuroendocrine stress response. Moreover, with the exception of blood pressure responses, all stress parameters were enhanced compared to the standard CPT. This shows that the bilateral feet CPT is a valid alternative to the standard CPT. The third experiment further validates the bilateral feet CPT and its corresponding control procedure by employing it in a typical application scenario. Specifically, the bilateral feet CPT was used to modulate retrieval of event files in a distractor-response binding paradigm that required lateralized bimanual responses. Again, the bilateral feet CPT induced significant increases in heart rate, blood pressure and cortisol, no such increases could be observed in the warm water control condition. Moreover, stressed participants showed diminished retrieval compared to controls. These results provide further evidence for the feasibility and validity of the bilateral feet CPT and its warm water control procedure. Together the experiments presented here highlight the usefulness of the CPT as a tool in psychophysiological stress research. It is especially well suited to test hypothesis concerning stress effects on memory processes and its applicability can be further increased by the bilateral feet modification.