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      Thinking Outside a Less Intact Box: Thalamic Dopamine D2 Receptor Densities Are Negatively Related to Psychometric Creativity in Healthy Individuals

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          Abstract

          Several lines of evidence support that dopaminergic neurotransmission plays a role in creative thought and behavior. Here, we investigated the relationship between creative ability and dopamine D2 receptor expression in healthy individuals, with a focus on regions where aberrations in dopaminergic function have previously been associated with psychotic symptoms and a genetic liability to schizophrenia. Scores on divergent thinking tests (Inventiveness battery, Berliner Intelligenz Struktur Test) were correlated with regional D2 receptor densities, as measured by Positron Emission Tomography, and the radioligands [ 11C]raclopride and [ 11C]FLB 457. The results show a negative correlation between divergent thinking scores and D2 density in the thalamus, also when controlling for age and general cognitive ability. Hence, the results demonstrate that the D2 receptor system, and specifically thalamic function, is important for creative performance, and may be one crucial link between creativity and psychopathology. We suggest that decreased D2 receptor densities in the thalamus lower thalamic gating thresholds, thus increasing thalamocortical information flow. In healthy individuals, who do not suffer from the detrimental effects of psychiatric disease, this may increase performance on divergent thinking tests. In combination with the cognitive functions of higher order cortical networks, this could constitute a basis for the generative and selective processes that underlie real life creativity.

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          The principal features and mechanisms of dopamine modulation in the prefrontal cortex.

          Mesocortical [corrected] dopamine (DA) inputs to the prefrontal cortex (PFC) play a critical role in normal cognitive process and neuropsychiatic pathologies. This DA input regulates aspects of working memory function, planning and attention, and its dysfunctions may underlie positive and negative symptoms and cognitive deficits associated with schizophrenia. Despite intense research, there is still a lack of clear understanding of the basic principles of actions of DA in the PFC. In recent years, there has been considerable efforts by many groups to understand the cellular mechanisms of DA modulation of PFC neurons. However, the results of these efforts often lead to contradictions and controversies. One principal feature of DA that is agreed by most researchers is that DA is a neuromodulator and is clearly not an excitatory or inhibitory neurotransmitter. The present article aims to identify certain principles of DA mechanisms by drawing on published, as well as unpublished data from PFC and other CNS sites to shed light on aspects of DA neuromodulation and address some of the existing controversies. Eighteen key features about DA modulation have been identified. These points directly impact on the end result of DA neuromodulation, and in some cases explain why DA does not yield identical effects under all experimental conditions. It will become apparent that DA's actions in PFC are subtle and depend on a variety of factors that can no longer be ignored. Some of these key factors include distinct bell-shaped dose-response profiles of postsynaptic DA effects, different postsynaptic responses that are contingent on the duration of DA receptor stimulation, prolonged duration effects, bidirectional effects following activation of D1 and D2 classes of receptors and membrane potential state and history dependence of subsequent DA actions. It is hoped that these factors will be borne in mind in future research and as a result a more consistent picture of DA neuromodulation in the PFC will emerge. Based on these factors, a theory is proposed for DA's action in PFC. This theory suggests that DA acts to expand or contract the breadth of information held in working memory buffers in PFC networks.
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            The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia.

            There is now general consensus that at least some of the cognitive deficits in schizophrenia are related to dysfunctions in the prefrontal cortex (PFC) dopamine (DA) system. At the cellular and synaptic level, the effects of DA in PFC via D1- and D2-class receptors are highly complex, often apparently opposing, and hence difficult to understand with regard to their functional implications. Biophysically realistic computational models have provided valuable insights into how the effects of DA on PFC neurons and synaptic currents as measured in vitro link up to the neural network and cognitive levels. They suggest the existence of two discrete dynamical regimes, a D1-dominated state characterized by a high energy barrier among different network patterns that favors robust online maintenance of information and a D2-dominated state characterized by a low energy barrier that is beneficial for flexible and fast switching among representational states. These predictions are consistent with a variety of electrophysiological, neuroimaging, and behavioral results in humans and nonhuman species. Moreover, these biophysically based models predict that imbalanced D1:D2 receptor activation causing extremely low or extremely high energy barriers among activity states could lead to the emergence of cognitive, positive, and negative symptoms observed in schizophrenia. Thus, combined experimental and computational approaches hold the promise of allowing a detailed mechanistic understanding of how DA alters information processing in normal and pathological conditions, thereby potentially providing new routes for the development of pharmacological treatments for schizophrenia.
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              The creative brain: investigation of brain activity during creative problem solving by means of EEG and FMRI.

              Cortical activity in the EEG alpha band has proven to be particularly sensitive to creativity-related demands, but its functional meaning in the context of creative cognition has not been clarified yet. Specifically, increases in alpha activity (i.e., alpha synchronisation) in response to creative thinking can be interpreted in different ways: As a functional correlate of cortical idling, as a sign of internal top-down activity or, more specifically, as selective inhibition of brain regions. We measured brain activity during creative thinking in two studies employing different neurophysiological measurement methods (EEG and fMRI). In both studies, participants worked on four verbal tasks differentially drawing on creative idea generation. The EEG study revealed that the generation of original ideas was associated with alpha synchronisation in frontal brain regions and with a diffuse and widespread pattern of alpha synchronisation over parietal cortical regions. The fMRI study revealed that task performance was associated with strong activation in frontal regions of the left hemisphere. In addition, we found task-specific effects in parietotemporal brain areas. The findings suggest that EEG alpha band synchronisation during creative thinking can be interpreted as a sign of active cognitive processes rather than cortical idling.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                17 May 2010
                : 5
                : 5
                : e10670
                Affiliations
                [1 ]Neuropediatric Research Unit, Department of Women's and Children's Health and Stockholm Brain Institute, Karolinska Institutet, Stockholm, Sweden
                [2 ]Psychiatry Section, Department of Clinical Neuroscience and Stockholm Brain Institute, Karolinska Institutet, Stockholm, Sweden
                [3 ]Human Motor Control Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
                University of Minnesota, United States of America
                Author notes

                Conceived and designed the experiments: OdM SC LF FU. Performed the experiments: OdM SC AK. Analyzed the data: OdM. Contributed reagents/materials/analysis tools: OdM SC. Wrote the paper: OdM FU. Interpretation of data: SC AK LF FU. Revision of paper: SC AK LF.

                Article
                10-PONE-RA-16116R1
                10.1371/journal.pone.0010670
                2871784
                20498850
                a21d4543-2b76-4302-aee4-3505c248bfcd
                de Manzano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 7 February 2010
                : 11 April 2010
                Page count
                Pages: 6
                Categories
                Research Article
                Neuroscience/Cognitive Neuroscience
                Neuroscience/Psychology
                Neuroscience/Experimental Psychology

                Uncategorized
                Uncategorized

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