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      Effects of Ginkgo biloba extract EGb 761® on cognitive control functions, mental activity of the prefrontal cortex and stress reactivity in elderly adults with subjective memory impairment – a randomized double‐blind placebo‐controlled trial

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          Abstract

          Objective

          Cognitive control as well as stress reactivity is assumed to depend on prefrontal dopamine and decline with age. Because Ginkgo biloba extract EGb761® increases prefrontal dopamine in animals, we assessed its effects on cognitive functions related to prefrontal dopamine.

          Methods

          Effects of 240‐mg EGb761® daily on task‐set‐switching, response‐inhibition, delayed response, prospective‐memory, task‐related fMRI‐BOLD‐signals and the Trier Social Stress‐Test were explored in a randomized, placebo‐controlled, double‐blind pilot‐trial in 61 elderly volunteers with subjective memory impairment.

          Results

          Baseline‐fMRI‐data showed BOLD‐responses in regions commonly activated by the specific tasks. Task‐switch‐costs decreased with EGb761® compared to placebo (ANOVA‐interaction: Group × Time × Switch‐Costs p = 0.018, multiple tests uncorrected), indicating improved cognitive flexibility. Go–NoGo‐task reaction‐times corrected for error‐rates indicated a trend for improved response inhibition. No treatment effects were found for the delayed response and prospective‐memory tasks and fMRI‐data. A non‐significant trend indicated a potentially accelerated endocrine stress‐recovery. EGb761® was safe and well tolerated.

          Conclusion

          We observed indications for improved cognitive flexibility without changes in brain activation, suggesting increased processing efficiency with EGb761®. Together with a trend for improved response inhibition results are compatible with mild enhancement of prefrontal dopamine. These conclusions on potential beneficial effect of EGb761® on prefrontal dopaminergic functions should be confirmed by direct measurements. © 2016 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd.

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          Most cited references 69

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          Inverted-U-shaped dopamine actions on human working memory and cognitive control.

          Brain dopamine (DA) has long been implicated in cognitive control processes, including working memory. However, the precise role of DA in cognition is not well-understood, partly because there is large variability in the response to dopaminergic drugs both across different behaviors and across different individuals. We review evidence from a series of studies with experimental animals, healthy humans, and patients with Parkinson's disease, which highlight two important factors that contribute to this large variability. First, the existence of an optimum DA level for cognitive function implicates the need to take into account baseline levels of DA when isolating the effects of DA. Second, cognitive control is a multifactorial phenomenon, requiring a dynamic balance between cognitive stability and cognitive flexibility. These distinct components might implicate the prefrontal cortex and the striatum, respectively. Manipulating DA will thus have paradoxical consequences for distinct cognitive control processes, depending on distinct basal or optimal levels of DA in different brain regions. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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            Task switching.

            Everyday life requires frequent shifts between cognitive tasks. Research reviewed in this article probes the control processes that reconfigure mental resources for a change of task by requiring subjects to switch frequently among a small set of simple tasks. Subjects' responses are substantially slower and, usually, more error-prone immediately after a task switch. This 'switch cost' is reduced, but not eliminated, by an opportunity for preparation. It seems to result from both transient and long-term carry-over of 'task-set' activation and inhibition as well as time consumed by task-set reconfiguration processes. Neuroimaging studies of task switching have revealed extra activation in numerous brain regions when subjects prepare to change tasks and when they perform a changed task, but we cannot yet separate 'controlling' from 'controlled' regions.
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              The neuropsychopharmacology of fronto-executive function: monoaminergic modulation.

              We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.
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                Author and article information

                Journal
                Hum Psychopharmacol
                Hum Psychopharmacol
                10.1002/(ISSN)1099-1077
                HUP
                Human Psychopharmacology
                John Wiley and Sons Inc. (Hoboken )
                0885-6222
                1099-1077
                05 May 2016
                May 2016
                : 31
                : 3 ( doiID: 10.1002/hup.v31.3 )
                : 227-242
                Affiliations
                [ 1 ] Department of PsychologyTechnische Universität Dresden DresdenGermany
                [ 2 ] Neuroimaging CentreTechnische Universität Dresden DresdenGermany
                [ 3 ] Institute for Clinical Pharmacology, Faculty of Medicine Carl Gustav CarusTechnische Universität Dresden DresdenGermany
                [ 4 ] Clinical Research Center Hannover & Institute for Clinical PharmacologyHannover Medical School HannoverGermany
                [ 5 ]Dr. Willmar Schwabe GmbH & Co. KG KarlsruheGermany
                Author notes
                [* ]Correspondence to: Stefanie Beck, Technische Universitaet Dresden, Faculty for Mathematic and Natural Science, Department of Psychology, Professorship for General Psychology, Zellescher Weg 17, 01062 Dresden, Germany. Tel: +49 351 463 346 76; Fax: +49 351 463 33522 E‐mail: Stefanie.Beck@ 123456tu-dresden.de
                Article
                HUP2534 HUP-15-0039.R2
                10.1002/hup.2534
                5084772
                27147264
                © 2016 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Pages: 16
                Product
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                hup2534
                hup2534-hdr-0001
                May 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.6 mode:remove_FC converted:28.10.2016

                Pharmacology & Pharmaceutical medicine

                cognitive control, dopamine, fmri, egb 761, ginkgo, task switch

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