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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD<inline-graphic xlink:href="permznlpap0000n1.jpg"><alt-text>(e–Pub ahead of print)</alt-text>
</inline-graphic>
</title>
<author><name sortKey="Van Eimeren, T" sort="Van Eimeren, T" uniqKey="Van Eimeren T" first="T." last="Van Eimeren">T. Van Eimeren</name>
</author>
<author><name sortKey="Pellecchia, G" sort="Pellecchia, G" uniqKey="Pellecchia G" first="G." last="Pellecchia">G. Pellecchia</name>
</author>
<author><name sortKey="Cilia, R" sort="Cilia, R" uniqKey="Cilia R" first="R." last="Cilia">R. Cilia</name>
</author>
<author><name sortKey="Ballanger, B" sort="Ballanger, B" uniqKey="Ballanger B" first="B." last="Ballanger">B. Ballanger</name>
</author>
<author><name sortKey="Steeves, T D L" sort="Steeves, T D L" uniqKey="Steeves T" first="T. D. L." last="Steeves">T. D. L. Steeves</name>
</author>
<author><name sortKey="Houle, S" sort="Houle, S" uniqKey="Houle S" first="S." last="Houle">S. Houle</name>
</author>
<author><name sortKey="Miyasaki, J M" sort="Miyasaki, J M" uniqKey="Miyasaki J" first="J. M." last="Miyasaki">J. M. Miyasaki</name>
</author>
<author><name sortKey="Zurowski, M" sort="Zurowski, M" uniqKey="Zurowski M" first="M." last="Zurowski">M. Zurowski</name>
</author>
<author><name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name>
</author>
<author><name sortKey="Strafella, A P" sort="Strafella, A P" uniqKey="Strafella A" first="A. P." last="Strafella">A. P. Strafella</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20926784</idno>
<idno type="pmc">3033606</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033606</idno>
<idno type="RBID">PMC:3033606</idno>
<idno type="doi">10.1212/WNL.0b013e3181fc27fa</idno>
<date when="2010">2010</date>
<idno type="wicri:Area/Pmc/Corpus">000322</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000322</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD<inline-graphic xlink:href="permznlpap0000n1.jpg"><alt-text>(e–Pub ahead of print)</alt-text>
</inline-graphic>
</title>
<author><name sortKey="Van Eimeren, T" sort="Van Eimeren, T" uniqKey="Van Eimeren T" first="T." last="Van Eimeren">T. Van Eimeren</name>
</author>
<author><name sortKey="Pellecchia, G" sort="Pellecchia, G" uniqKey="Pellecchia G" first="G." last="Pellecchia">G. Pellecchia</name>
</author>
<author><name sortKey="Cilia, R" sort="Cilia, R" uniqKey="Cilia R" first="R." last="Cilia">R. Cilia</name>
</author>
<author><name sortKey="Ballanger, B" sort="Ballanger, B" uniqKey="Ballanger B" first="B." last="Ballanger">B. Ballanger</name>
</author>
<author><name sortKey="Steeves, T D L" sort="Steeves, T D L" uniqKey="Steeves T" first="T. D. L." last="Steeves">T. D. L. Steeves</name>
</author>
<author><name sortKey="Houle, S" sort="Houle, S" uniqKey="Houle S" first="S." last="Houle">S. Houle</name>
</author>
<author><name sortKey="Miyasaki, J M" sort="Miyasaki, J M" uniqKey="Miyasaki J" first="J. M." last="Miyasaki">J. M. Miyasaki</name>
</author>
<author><name sortKey="Zurowski, M" sort="Zurowski, M" uniqKey="Zurowski M" first="M." last="Zurowski">M. Zurowski</name>
</author>
<author><name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name>
</author>
<author><name sortKey="Strafella, A P" sort="Strafella, A P" uniqKey="Strafella A" first="A. P." last="Strafella">A. P. Strafella</name>
</author>
</analytic>
<series><title level="j">Neurology</title>
<idno type="ISSN">0028-3878</idno>
<idno type="eISSN">1526-632X</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Objective:</title>
<p>Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).</p>
</sec>
<sec><title>Methods:</title>
<p>Following overnight withdrawal of antiparkinsonian medication, patients were studied with H<sub>2</sub>
<sup>15</sup>
O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.</p>
</sec>
<sec><title>Results:</title>
<p>We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.</p>
</sec>
<sec><title>Conclusions:</title>
<p>We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions—outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)—together with restricted access of those areas to executive control (external pallidum)—may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.</p>
</sec>
<sec><title>GLOSSARY</title>
<def-list list-type="abr"><def-item><term><bold>ANOVA</bold>
</term>
<def><p> = analysis of variance; </p>
</def>
</def-item>
<def-item><term><bold>DA</bold>
</term>
<def><p> = dopamine agonist; </p>
</def>
</def-item>
<def-item><term><bold>G-SAS</bold>
</term>
<def><p> = Gambling Symptom Assessment Scale; </p>
</def>
</def-item>
<def-item><term><bold>GPe</bold>
</term>
<def><p> = external pallidum; </p>
</def>
</def-item>
<def-item><term><bold>MNI</bold>
</term>
<def><p> = Montréal Neurological Institute; </p>
</def>
</def-item>
<def-item><term><bold>OFC</bold>
</term>
<def><p> = orbitofrontal cortex; </p>
</def>
</def-item>
<def-item><term><bold>PD</bold>
</term>
<def><p> = Parkinson disease; </p>
</def>
</def-item>
<def-item><term><bold>rCBF</bold>
</term>
<def><p> = regional cerebral blood flow; </p>
</def>
</def-item>
<def-item><term><bold>RCZ</bold>
</term>
<def><p> = rostral cingulated zone; </p>
</def>
</def-item>
<def-item><term><bold>UPDRS</bold>
</term>
<def><p> = Unified Parkinson's Disease Rating Scale.</p>
</def>
</def-item>
</def-list>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neurology</journal-id>
<journal-title-group><journal-title>Neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0028-3878</issn>
<issn pub-type="epub">1526-632X</issn>
<publisher><publisher-name>American Academy of Neurology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20926784</article-id>
<article-id pub-id-type="pmc">3033606</article-id>
<article-id pub-id-type="publisher-id">znl04310001711</article-id>
<article-id pub-id-type="doi">10.1212/WNL.0b013e3181fc27fa</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD<inline-graphic xlink:href="permznlpap0000n1.jpg"><alt-text>(e–Pub ahead of print)</alt-text>
</inline-graphic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>van Eimeren</surname>
<given-names>T.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Pellecchia</surname>
<given-names>G.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Cilia</surname>
<given-names>R.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Ballanger</surname>
<given-names>B.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Steeves</surname>
<given-names>T.D.L.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Houle</surname>
<given-names>S.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Miyasaki</surname>
<given-names>J.M.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Zurowski</surname>
<given-names>M.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Lang</surname>
<given-names>A.E.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Strafella</surname>
<given-names>A.P.</given-names>
</name>
<degrees>MD, PhD</degrees>
</contrib>
</contrib-group>
<aff id="d26e80">From the Division of Brain, Imaging and Behaviour-Systems Neuroscience, BIB-SN (T.v.E., G.P., R.C., B.B., A.P.S.), Toronto Western Research Institute; Movement Disorders Centre (T.D.L.S., J.M., M.Z., A.E.L., A.P.S.), Toronto Western Hospital; and CAMH-PET Centre (T.v.E., G.P., R.C., B.B., S.H., A.P.S.), University of Toronto, Canada.<break></break>
</aff>
<pub-date pub-type="ppub"><day>9</day>
<month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>9</day>
<month>11</month>
<year>2011</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
. </pmc-comment>
<volume>75</volume>
<issue>19</issue>
<fpage>1711</fpage>
<lpage>1716</lpage>
<permissions><copyright-statement>Copyright © 2010 by AAN Enterprises, Inc.</copyright-statement>
</permissions>
<abstract><sec><title>Objective:</title>
<p>Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).</p>
</sec>
<sec><title>Methods:</title>
<p>Following overnight withdrawal of antiparkinsonian medication, patients were studied with H<sub>2</sub>
<sup>15</sup>
O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.</p>
</sec>
<sec><title>Results:</title>
<p>We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.</p>
</sec>
<sec><title>Conclusions:</title>
<p>We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions—outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)—together with restricted access of those areas to executive control (external pallidum)—may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.</p>
</sec>
<sec><title>GLOSSARY</title>
<def-list list-type="abr"><def-item><term><bold>ANOVA</bold>
</term>
<def><p> = analysis of variance; </p>
</def>
</def-item>
<def-item><term><bold>DA</bold>
</term>
<def><p> = dopamine agonist; </p>
</def>
</def-item>
<def-item><term><bold>G-SAS</bold>
</term>
<def><p> = Gambling Symptom Assessment Scale; </p>
</def>
</def-item>
<def-item><term><bold>GPe</bold>
</term>
<def><p> = external pallidum; </p>
</def>
</def-item>
<def-item><term><bold>MNI</bold>
</term>
<def><p> = Montréal Neurological Institute; </p>
</def>
</def-item>
<def-item><term><bold>OFC</bold>
</term>
<def><p> = orbitofrontal cortex; </p>
</def>
</def-item>
<def-item><term><bold>PD</bold>
</term>
<def><p> = Parkinson disease; </p>
</def>
</def-item>
<def-item><term><bold>rCBF</bold>
</term>
<def><p> = regional cerebral blood flow; </p>
</def>
</def-item>
<def-item><term><bold>RCZ</bold>
</term>
<def><p> = rostral cingulated zone; </p>
</def>
</def-item>
<def-item><term><bold>UPDRS</bold>
</term>
<def><p> = Unified Parkinson's Disease Rating Scale.</p>
</def>
</def-item>
</def-list>
</sec>
</abstract>
</article-meta>
<notes><p>Address correspondence and reprint requests to Dr. A.P. Strafella, Toronto Western Hospital and Research Institute and CAMH-PET Centre, Toronto, ON, Canada <email>antonio.strafella@uhnres.utoronto.ca</email>
</p>
<p>Editorial, page 1668</p>
<p>Supplemental data at <ext-link ext-link-type="uri" xlink:href="www.neurology.org">www.neurology.org</ext-link>
</p>
<p><italic>e-Pub ahead of print on October 6, 2010, at</italic>
<ext-link ext-link-type="uri" xlink:href="www.neurology.org">www.neurology.org</ext-link>
.</p>
<p><italic>Study funding:</italic>
Supported by the Ontario Problem Gambling Research Centre and Canadian Institutes of Health Research (CIHR) (MOP-64423 to A.P.S.). A.P.S. is supported by the CIHR New Investigator Research Award.</p>
<p><italic>Disclosure:</italic>
Author disclosures are provided at the end of the article.</p>
<p>Received April 2, 2010. Accepted in final form July 19, 2010.</p>
</notes>
</front>
</pmc>
</record>
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