Simulating Neurocognitive Aging: Effects of a Dopaminergic Antagonist on Brain Activity During Working Memory
Background Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity. Methods We used an experimental-pharmacological functional magnetic resonance imaging (...
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| Veröffentlicht in: | Biological psychiatry (1969) 2010, Vol.67 (6), p.575-580 |
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| container_title | Biological psychiatry (1969) |
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| creator | Fischer, Håkan Nyberg, Lars Karlsson, Sari Karlsson, Per Brehmer, Yvonne Rieckmann, Anna MacDonald, Stuart W.S Farde, Lars Bäckman, Lars |
| description | Background Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity. Methods We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [11 C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults. Results An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response. Conclusions These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks. |
| doi_str_mv | 10.1016/j.biopsych.2009.12.013 |
| format | Article |
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Methods We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [11 C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults. Results An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response. Conclusions These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.</description><identifier>ISSN: 0006-3223</identifier><identifier>ISSN: 1873-2402</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2009.12.013</identifier><identifier>PMID: 20138255</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Aging ; Aging - physiology ; Analysis of Variance ; antagonist ; Benzazepines ; Benzazepines - pharmacology ; Biological and medical sciences ; blood ; blood supply ; Brain ; Brain - blood supply ; Brain - diagnostic imaging ; Brain - drug effects ; Brain Mapping ; Computer-Assisted ; D1 receptors ; Diagnostic radiology ; Diagnostisk radiologi ; dopamine ; Dopamine Antagonists ; Dopamine Antagonists - pharmacology ; drug effects ; Female ; fMRI ; Fysiologi och farmakologi ; Humans ; Image Processing ; Image Processing, Computer-Assisted - methods ; Kirurgi ; Magnetic Resonance Imaging ; Magnetic Resonance Imaging - methods ; Male ; Medical sciences ; MEDICIN ; MEDICINE ; Memory ; Memory, Short-Term - drug effects ; Memory, Short-Term - physiology ; methods ; Neuropsychological Tests ; Oxygen ; Oxygen - blood ; pharmacology ; physiology ; Physiology and pharmacology ; Positron-Emission Tomography ; Positron-Emission Tomography - methods ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Radiological research ; Radiologisk forskning ; radionuclide imaging ; Short-Term ; Single-Blind Method ; Space Perception ; Space Perception - drug effects ; Space Perception - physiology ; spatial working memory ; Surgery ; Young Adult</subject><ispartof>Biological psychiatry (1969), 2010, Vol.67 (6), p.575-580</ispartof><rights>Society of Biological Psychiatry</rights><rights>2010 Society of Biological Psychiatry</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c667t-181c558056edcff0b5b9b95782a07d4c36e78f0ab37882d652007f0b0f395c1d3</citedby><cites>FETCH-LOGICAL-c667t-181c558056edcff0b5b9b95782a07d4c36e78f0ab37882d652007f0b0f395c1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006322309014747$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,4009,27902,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22504751$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20138255$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-84983$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-31985$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/150918$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:120140788$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Fischer, Håkan</creatorcontrib><creatorcontrib>Nyberg, Lars</creatorcontrib><creatorcontrib>Karlsson, Sari</creatorcontrib><creatorcontrib>Karlsson, Per</creatorcontrib><creatorcontrib>Brehmer, Yvonne</creatorcontrib><creatorcontrib>Rieckmann, Anna</creatorcontrib><creatorcontrib>MacDonald, Stuart W.S</creatorcontrib><creatorcontrib>Farde, Lars</creatorcontrib><creatorcontrib>Bäckman, Lars</creatorcontrib><title>Simulating Neurocognitive Aging: Effects of a Dopaminergic Antagonist on Brain Activity During Working Memory</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>Background Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity. Methods We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [11 C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults. Results An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response. Conclusions These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.</description><subject>Adult</subject><subject>Aged</subject><subject>Aging</subject><subject>Aging - physiology</subject><subject>Analysis of Variance</subject><subject>antagonist</subject><subject>Benzazepines</subject><subject>Benzazepines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>blood</subject><subject>blood supply</subject><subject>Brain</subject><subject>Brain - blood supply</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - drug effects</subject><subject>Brain Mapping</subject><subject>Computer-Assisted</subject><subject>D1 receptors</subject><subject>Diagnostic radiology</subject><subject>Diagnostisk radiologi</subject><subject>dopamine</subject><subject>Dopamine Antagonists</subject><subject>Dopamine Antagonists - pharmacology</subject><subject>drug effects</subject><subject>Female</subject><subject>fMRI</subject><subject>Fysiologi och farmakologi</subject><subject>Humans</subject><subject>Image Processing</subject><subject>Image Processing, Computer-Assisted - methods</subject><subject>Kirurgi</subject><subject>Magnetic Resonance Imaging</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Memory</subject><subject>Memory, Short-Term - drug effects</subject><subject>Memory, Short-Term - physiology</subject><subject>methods</subject><subject>Neuropsychological Tests</subject><subject>Oxygen</subject><subject>Oxygen - blood</subject><subject>pharmacology</subject><subject>physiology</subject><subject>Physiology and pharmacology</subject><subject>Positron-Emission Tomography</subject><subject>Positron-Emission Tomography - methods</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Radiological research</subject><subject>Radiologisk forskning</subject><subject>radionuclide imaging</subject><subject>Short-Term</subject><subject>Single-Blind Method</subject><subject>Space Perception</subject><subject>Space Perception - drug effects</subject><subject>Space Perception - physiology</subject><subject>spatial working memory</subject><subject>Surgery</subject><subject>Young Adult</subject><issn>0006-3223</issn><issn>1873-2402</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0stu1DAUBuAIgei08AqVN4gFzeBLHDssKoZOuUgFFuWytBzHCZ5J7GDHRfP2OJppkZCgK9tH3zmO4j_LThFcIojKl5tlbdwYdurHEkNYLRFeQkQeZAvEGclxAfHDbAEhLHOCMTnKjkPYpCPDGD3OjnCyHFO6yIZrM8ReTsZ24JOO3inXWTOZGw1WXSq-Apdtq9UUgGuBBGs3ysFY7TujwMpOsnPWhAk4C954aSxYqdRrph1YRz_P_O78dl4_6sH53ZPsUSv7oJ8e1pPs69vLLxfv86vP7z5crK5yVZZsyhFHilIOaakb1bawpnVVV5RxLCFrCkVKzXgLZU0Y57gpafoFLDHYkooq1JCTLN_PDb_0GGsxejNIvxNOGnEobdNOC0oJgfi_voujSKUuzh5RWCGe_Nk__dp8WwnnOxGHKAiqOE38xf08RMGLipOkn-_16N3PqMMkBhOU7ntptYtBMEIowbAokyz3UnkXgtft3WQExRwTsRG3MRFzTATCIj19ajw9XBHrQTd3bbe5SODZAcigZN96aZUJfxymsGAUJfd673R6zRujvQjKaKt0Y3xKjWicuf9bzv8aoXpjTbp1q3c6bFz0NmVFIBFSg7ieQz1nGlYQFaxg5DertvWK</recordid><startdate>2010</startdate><enddate>2010</enddate><creator>Fischer, Håkan</creator><creator>Nyberg, Lars</creator><creator>Karlsson, Sari</creator><creator>Karlsson, Per</creator><creator>Brehmer, Yvonne</creator><creator>Rieckmann, Anna</creator><creator>MacDonald, Stuart W.S</creator><creator>Farde, Lars</creator><creator>Bäckman, Lars</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG7</scope><scope>D93</scope><scope>F1U</scope></search><sort><creationdate>2010</creationdate><title>Simulating Neurocognitive Aging: Effects of a Dopaminergic Antagonist on Brain Activity During Working Memory</title><author>Fischer, Håkan ; Nyberg, Lars ; Karlsson, Sari ; Karlsson, Per ; Brehmer, Yvonne ; Rieckmann, Anna ; MacDonald, Stuart W.S ; Farde, Lars ; Bäckman, Lars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c667t-181c558056edcff0b5b9b95782a07d4c36e78f0ab37882d652007f0b0f395c1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aging</topic><topic>Aging - physiology</topic><topic>Analysis of Variance</topic><topic>antagonist</topic><topic>Benzazepines</topic><topic>Benzazepines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>blood</topic><topic>blood supply</topic><topic>Brain</topic><topic>Brain - blood supply</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - drug effects</topic><topic>Brain Mapping</topic><topic>Computer-Assisted</topic><topic>D1 receptors</topic><topic>Diagnostic radiology</topic><topic>Diagnostisk radiologi</topic><topic>dopamine</topic><topic>Dopamine Antagonists</topic><topic>Dopamine Antagonists - pharmacology</topic><topic>drug effects</topic><topic>Female</topic><topic>fMRI</topic><topic>Fysiologi och farmakologi</topic><topic>Humans</topic><topic>Image Processing</topic><topic>Image Processing, Computer-Assisted - methods</topic><topic>Kirurgi</topic><topic>Magnetic Resonance Imaging</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Male</topic><topic>Medical sciences</topic><topic>MEDICIN</topic><topic>MEDICINE</topic><topic>Memory</topic><topic>Memory, Short-Term - drug effects</topic><topic>Memory, Short-Term - physiology</topic><topic>methods</topic><topic>Neuropsychological Tests</topic><topic>Oxygen</topic><topic>Oxygen - blood</topic><topic>pharmacology</topic><topic>physiology</topic><topic>Physiology and pharmacology</topic><topic>Positron-Emission Tomography</topic><topic>Positron-Emission Tomography - methods</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Radiological research</topic><topic>Radiologisk forskning</topic><topic>radionuclide imaging</topic><topic>Short-Term</topic><topic>Single-Blind Method</topic><topic>Space Perception</topic><topic>Space Perception - drug effects</topic><topic>Space Perception - physiology</topic><topic>spatial working memory</topic><topic>Surgery</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fischer, Håkan</creatorcontrib><creatorcontrib>Nyberg, Lars</creatorcontrib><creatorcontrib>Karlsson, Sari</creatorcontrib><creatorcontrib>Karlsson, Per</creatorcontrib><creatorcontrib>Brehmer, Yvonne</creatorcontrib><creatorcontrib>Rieckmann, Anna</creatorcontrib><creatorcontrib>MacDonald, Stuart W.S</creatorcontrib><creatorcontrib>Farde, Lars</creatorcontrib><creatorcontrib>Bäckman, Lars</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Stockholms universitet</collection><collection>SWEPUB Umeå universitet</collection><collection>SWEPUB Göteborgs universitet</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fischer, Håkan</au><au>Nyberg, Lars</au><au>Karlsson, Sari</au><au>Karlsson, Per</au><au>Brehmer, Yvonne</au><au>Rieckmann, Anna</au><au>MacDonald, Stuart W.S</au><au>Farde, Lars</au><au>Bäckman, Lars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simulating Neurocognitive Aging: Effects of a Dopaminergic Antagonist on Brain Activity During Working Memory</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2010</date><risdate>2010</risdate><volume>67</volume><issue>6</issue><spage>575</spage><epage>580</epage><pages>575-580</pages><issn>0006-3223</issn><issn>1873-2402</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Background Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity. Methods We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [11 C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults. Results An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response. Conclusions These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20138255</pmid><doi>10.1016/j.biopsych.2009.12.013</doi><tpages>6</tpages></addata></record> |
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| subjects | Adult Aged Aging Aging - physiology Analysis of Variance antagonist Benzazepines Benzazepines - pharmacology Biological and medical sciences blood blood supply Brain Brain - blood supply Brain - diagnostic imaging Brain - drug effects Brain Mapping Computer-Assisted D1 receptors Diagnostic radiology Diagnostisk radiologi dopamine Dopamine Antagonists Dopamine Antagonists - pharmacology drug effects Female fMRI Fysiologi och farmakologi Humans Image Processing Image Processing, Computer-Assisted - methods Kirurgi Magnetic Resonance Imaging Magnetic Resonance Imaging - methods Male Medical sciences MEDICIN MEDICINE Memory Memory, Short-Term - drug effects Memory, Short-Term - physiology methods Neuropsychological Tests Oxygen Oxygen - blood pharmacology physiology Physiology and pharmacology Positron-Emission Tomography Positron-Emission Tomography - methods Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Radiological research Radiologisk forskning radionuclide imaging Short-Term Single-Blind Method Space Perception Space Perception - drug effects Space Perception - physiology spatial working memory Surgery Young Adult |
| title | Simulating Neurocognitive Aging: Effects of a Dopaminergic Antagonist on Brain Activity During Working Memory |
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