Changes in Cortical Dopamine D1 Receptor Binding Associated with Cognitive Training

Neuropediatric Unit, Department of Woman and Child Health, Stockholm Brain Institute, Karolinska Institutet, Stockholm, Sweden.
Science (Impact Factor: 33.61). 03/2009; 323(5915):800-2. DOI: 10.1126/science.1166102
Source: PubMed


Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo.

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    • "Significant and lasting improvement in WM following working memory training has been reported in several populations with poor working memory skills, and transfer to some non-trained cognitive tasks has been observed (Klingberg et al., 2005; McNab et al., 2009; Olesen et al., 2004; Thorell et al., 2009; Westerberg and Klingberg, 2007; Westerberg et al., 2007). For example, Bickel et al. (2011) found that working memory training decreased delay discounting in stimulant users, suggesting greater preferences for larger-later rewards relative to smaller-sooner ones. "
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    ABSTRACT: Objective: Working memory impairment in individuals with chronic opioid dependence can play a major role in cognitive and treatment outcomes. Cognitive training targeting working memory shows promise for improved function in substance use disorders. To date, cognitive training has not been incorporated as an adjunctive treatment for opioid dependence. Methods: Methadone maintenance patients were randomly assigned to experimental (n=28) or active control (n=28) 25-session computerized training and run in parallel. Cognitive and drug use outcomes were assessed before and after training. Results: Participants in the experimental condition showed performance improvements on two of four working memory measures, and both groups improved on a third measure of working memory performance. Less frequent drug use was found in the experimental group than in the control group post-training. In contrast to previous findings with stimulant users, no significant effect of working memory training on delay discounting was found using either hypothetical or real rewards. There were no group differences on working memory outcome measures that were dissimilar from the training tasks, suggesting that another mechanism (e.g., increased distress tolerance) may have driven drug use results. Conclusions: Working memory training improves performance on some measures of working memory in methadone maintenance patients, and may impact drug use outcomes. Working memory training shows promise in patients with substance use disorders; however, further research is needed to understand the mechanisms through which performance is improved and drug use outcomes are impacted.
    Drug and alcohol dependence 09/2015; 156. DOI:10.1016/j.drugalcdep.2015.08.012 · 3.42 Impact Factor
    • "Not only does cognition depend on dopamine signaling but also cognitive training alters dopamine function . In fact, working memory training for 5 weeks altered the D1R binding potential in prefrontal and parietal cortices (McNab et al., 2009) and D2R binding potential in the striatum (Backman et al., 2011). One limitation of the current work arises from our sole use of female subjects. "
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    ABSTRACT: Increasing motivation can positively impact cognitive performance. Here we employed a cognitive timing task that allows us to detect changes in cognitive performance that are not influenced by general activity or arousal factors such as the speed or persistence of responding. This approach allowed us to manipulate motivation using three different methods; molecular/genetic, behavioral and pharmacological. Increased striatal D2Rs resulted in deficits in temporal discrimination. Switching off the transgene improved motivation in earlier studies, and here partially rescued the temporal discrimination deficit. To manipulate motivation behaviorally, we altered reward magnitude and found that increasing reward magnitude improved timing in control mice and partially rescued timing in the transgenic mice. Lastly, we manipulated motivation pharmacologically using a functionally selective 5-HT2C receptor ligand, SB242084, which we previously found to increase incentive motivation. SB242084 improved temporal discrimination in both control and transgenic mice. Thus, while there is a general intuitive belief that motivation can affect cognition, we here provide a direct demonstration that enhancing motivation, in a variety of ways, can be an effective strategy for enhancing temporal cognition. Understanding the interaction of motivation and cognition is of clinical significance since many psychiatric disorders are characterized by deficits in both domains. (PsycINFO Database Record
    Behavioral Neuroscience 09/2015; 129(5). DOI:10.1037/bne0000083 · 2.73 Impact Factor
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    • "Behavioral improvements after treatment were observed in the domain of WM (Vogt et al., 2009), as well as in linked cognitive functions (Nouchi et al., 2012) and, importantly, they transferred to the subjective appraisal of everyday life functioning (Johansson & Tornmalm, 2012). Imaging studies indicated that such behavioral effects are accompanied by changes in brain activation and structure (Brehmer et al., 2011; Takeuchi et al., 2011), in structural connectivity (Takeuchi et al., 2010), and in the neurotransmitter system (McNab et al., 2009). Nevertheless, not all studies yield consistent results and, currently, there is an intensive discussion if and under which Conditions WM training produces valid transfer effects (for a review, see Morrison & Chein, 2011). "
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    ABSTRACT: Deficits in working memory (WM) are commonly observed after brain injuries and cause severe impairments in patients' everyday life. It is still under debate if training can enhance or rehabilitate WM in case of malfunction. The current meta-analysis investigates this issue from a clinical point of view. It addresses under which conditions and for which target group WM training may be justifiable. Relevant WM training studies were identified by searching electronic literature databases with a comprehensive search term. In total, 103 studies, which added up to 112 independent group comparisons (N = 6,113 participants), were included in the analysis. Overall, WM training caused a moderate and long-lasting improvement in untrained WM tasks. Moreover, improvement of WM functioning led to sustainable better evaluation of everyday life functioning, however, effect sizes were small. Concerning transfer effects on other cognitive domains, long-lasting improvements with small effect sizes were observed in cognitive control and reasoning/intelligence. In contrast, small immediate, but no long-term effects were found for attention and long-term memory. Studies with brain injured patients demonstrated long-lasting improvements in WM functions with moderate to large effect sizes. A main moderator variable of intervention efficacy is the number of training sessions applied. WM training produces long-lasting beneficial effects which are strongly pronounced in patients with acquired brain injuries. This finding supports the application of WM training in clinical settings. To determine optimal training conditions, future studies must systematically investigate the characteristics of interventions as they are at present inevitably confounded. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Neuropsychology 08/2015; DOI:10.1037/neu0000227 · 3.27 Impact Factor
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