(Lack of) Effects of noradrenergic stimulation on human working memory performance
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ORIGINAL INVESTIGATION
(Lack of) Effects of noradrenergic stimulation on human working memory performance Nadine Wanke 1 & Jana Christina Müller 2 & Klaus Wiedemann 2 & Lars Schwabe 1 Received: 27 March 2020 / Accepted: 11 June 2020 # The Author(s) 2020
Abstract Rationale Working memory depends on prefrontal cortex functioning, which is particularly sensitive to levels of noradrenaline. Studies in non-human primates have shown that modest levels of noradrenaline improve working memory, and that higher levels of noradrenaline impair working memory performance. However, research in humans provided inconsistent findings concerning noradrenergic effects on working memory. Objective The present study aimed at assessing dose-dependent effects of yohimbine, an alpha-2 adrenoceptor antagonist, on working memory performance in healthy humans. We further aimed to explore a potential interactive effect between noradrenergic arousal and lack of control over aversive events on working memory performance. Methods We used a double-blind, fully crossed, placebo-controlled, between-subject design. Participants (N = 121) performed an adaptive n-back task before and after oral administration of either a placebo, 20 mg, or 40 mg yohimbine and a manipulation of controllability, during which participants could either learn to avoid electric shocks (controllability groups), had no instrumental control over shock administration (uncontrollability groups), or did not receive any shocks (no-shock control group). Results While no significant results of noradrenergic stimulation through yohimbine were obtained using conventional frequentist analyses, additional Bayesian analyses provided strong evidence for the absence of an association between pharmacological treatment and working memory performance. We further observed no effect of controllability and no interaction between noradrenergic stimulation and the manipulation of controllability. Conclusions Our results suggest that noradrenergic stimulation through yohimbine does not affect (non-spatial) working memory in healthy human participants. Keywords Yohimbine . Noradrenaline . Norepinephrine . Working memory . n-back . Prefrontal cortex . Learned helplessness
Introduction Working memory is a core cognitive function that is essential for goal-directed behavior. At a neural level, working memory relies heavily on the dorsolateral prefrontal cortex (Barbey et al. 2013; Cohen et al. 1997; D'Esposito and Postle 1999). This brain area is known to be regulated by catecholamines in general and noradrenaline in particular (Arnsten 2011; Robbins 2000). Increased noradrenergic arousal, mediated
* Lars Schwabe [email protected] 1
Department of Cognitive Psychology, University of Hamburg, 20146 Hamburg, Germany
2
Department of Psychiatry, University Clinic Hamburg-Eppendorf, Hamburg, Germany
by noradrenergic projections from the locus coeruleus to prefrontal areas, is assumed to be a driving force in the disruptive effect of stressful events on working memory function (Bogdanov and
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