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      Effects of Parkinson’s disease and dopamine on digit span measures of working memory

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          Abstract

          Rationale

          Parkinson’s disease (PD) impairs working memory (WM)—the ability to maintain items in memory for short periods of time and manipulate them. There is conflicting evidence on the nature of the deficits caused by the disease, and the potential beneficial and detrimental effects of dopaminergic medication on different WM processes.

          Objectives

          We hypothesised that PD impairs both maintenance and manipulation of items in WM and dopaminergic medications improve this in PD patients but impair it in healthy older adults.

          Methods

          We tested 68 PD patients ON and OFF their dopaminergic medication, 83 healthy age-matched controls, and 30 healthy older adults after placebo and levodopa administration. We used the digit span, a WM test with three components (forwards, backwards, and sequence recall) that differ in the amount of manipulation required. We analysed the maximum spans and the percentage of lists correctly recalled, which probe capacity of WM and the accuracy of the memory processes within this capacity, respectively.

          Results

          PD patients had lower WM capacity across all three digit span components, but only showed reduced percentage accuracy on the components requiring manipulation (backwards and sequence spans). Dopaminergic medication did not affect performance in PD patients. In healthy older adults, levodopa did not affect capacity, but did impair accuracy on one of the manipulation components (sequence), without affecting the other (backwards).

          Conclusions

          This suggests that the deficit of maintenance capacity and manipulation accuracy in PD patients is not primarily a dopaminergic one and supports a potential “overdosing” of intact manipulation mechanisms in healthy older adults by levodopa.

          Electronic supplementary material

          The online version of this article (10.1007/s00213-018-5058-6) contains supplementary material, which is available to authorized users.

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          Most cited references28

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          Working Memory: Theories, Models, and Controversies

          I present an account of the origins and development of the multicomponent approach to working memory, making a distinction between the overall theoretical framework, which has remained relatively stable, and the attempts to build more specific models within this framework. I follow this with a brief discussion of alternative models and their relationship to the framework. I conclude with speculations on further developments and a comment on the value of attempting to apply models and theories beyond the laboratory studies on which they are typically based.
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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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              The precision of visual working memory is set by allocation of a shared resource.

              The mechanisms underlying visual working memory have recently become controversial. One account proposes a small number of memory "slots," each capable of storing a single visual object with fixed precision. A contrary view holds that working memory is a shared resource, with no upper limit on the number of items stored; instead, the more items that are held in memory, the less precisely each can be recalled. Recent findings from a color report task have been taken as crucial new evidence in favor of the slot model. However, while this task has previously been thought of as a simple test of memory for color, here we show that performance also critically depends on memory for location. When errors in memory are considered for both color and location, performance on this task is in fact well explained by the resource model. These results demonstrate that visual working memory consists of a common resource distributed dynamically across the visual scene, with no need to invoke an upper limit on the number of objects represented.
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                Author and article information

                Contributors
                +44 (0)1174148186 , John.grogan@bristol.ac.uk
                Journal
                Psychopharmacology (Berl)
                Psychopharmacology (Berl.)
                Psychopharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0033-3158
                1432-2072
                12 October 2018
                12 October 2018
                2018
                : 235
                : 12
                : 3443-3450
                Affiliations
                [1 ]ISNI 0000 0004 0417 1173, GRID grid.416201.0, Bristol Brain Centre, Elgar House, , Southmead Hospital, ; Bristol, BS10 5NB UK
                [2 ]ISNI 0000 0004 0380 7336, GRID grid.410421.2, University Hospitals Bristol, ; Bristol, UK
                [3 ]ISNI 0000 0004 0380 7221, GRID grid.418484.5, North Bristol NHS Trust, ; Bristol, UK
                Author information
                http://orcid.org/0000-0002-0463-8904
                Article
                5058
                10.1007/s00213-018-5058-6
                6267128
                30315362
                a6b4e523-798f-4dc3-9ff1-75078aba3a28
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 10 May 2018
                : 2 October 2018
                Funding
                Funded by: Wellcome Trust (GB)
                Award ID: 097081/Z/11/Z
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100011699, BRACE;
                Award ID: BRI17/15
                Award Recipient :
                Categories
                Original Investigation
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Pharmacology & Pharmaceutical medicine
                parkinson’s disease,dopamine,working memory,levodopa,short-term memory

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