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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson’s Disease</title>
<author><name sortKey="Hirano, Shigeki" sort="Hirano, Shigeki" uniqKey="Hirano S" first="Shigeki" last="Hirano">Shigeki Hirano</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Asanuma, Kotaro" sort="Asanuma, Kotaro" uniqKey="Asanuma K" first="Kotaro" last="Asanuma">Kotaro Asanuma</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Neurology, Tokushima University Hospital Tokushima-City, Japan 770-8503</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ma, Yilong" sort="Ma, Yilong" uniqKey="Ma Y" first="Yilong" last="Ma">Yilong Ma</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tang, Chengke" sort="Tang, Chengke" uniqKey="Tang C" first="Chengke" last="Tang">Chengke Tang</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Feigin, Andrew" sort="Feigin, Andrew" uniqKey="Feigin A" first="Andrew" last="Feigin">Andrew Feigin</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dhawan, Vijay" sort="Dhawan, Vijay" uniqKey="Dhawan V" first="Vijay" last="Dhawan">Vijay Dhawan</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carbon, Maren" sort="Carbon, Maren" uniqKey="Carbon M" first="Maren" last="Carbon">Maren Carbon</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Eidelberg, David" sort="Eidelberg, David" uniqKey="Eidelberg D" first="David" last="Eidelberg">David Eidelberg</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">18417699</idno>
<idno type="pmc">2577921</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577921</idno>
<idno type="RBID">PMC:2577921</idno>
<idno type="doi">10.1523/JNEUROSCI.0582-08.2008</idno>
<date when="2008">2008</date>
<idno type="wicri:Area/Pmc/Corpus">000207</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000207</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson’s Disease</title>
<author><name sortKey="Hirano, Shigeki" sort="Hirano, Shigeki" uniqKey="Hirano S" first="Shigeki" last="Hirano">Shigeki Hirano</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Asanuma, Kotaro" sort="Asanuma, Kotaro" uniqKey="Asanuma K" first="Kotaro" last="Asanuma">Kotaro Asanuma</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Neurology, Tokushima University Hospital Tokushima-City, Japan 770-8503</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ma, Yilong" sort="Ma, Yilong" uniqKey="Ma Y" first="Yilong" last="Ma">Yilong Ma</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tang, Chengke" sort="Tang, Chengke" uniqKey="Tang C" first="Chengke" last="Tang">Chengke Tang</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Feigin, Andrew" sort="Feigin, Andrew" uniqKey="Feigin A" first="Andrew" last="Feigin">Andrew Feigin</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dhawan, Vijay" sort="Dhawan, Vijay" uniqKey="Dhawan V" first="Vijay" last="Dhawan">Vijay Dhawan</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carbon, Maren" sort="Carbon, Maren" uniqKey="Carbon M" first="Maren" last="Carbon">Maren Carbon</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Eidelberg, David" sort="Eidelberg, David" uniqKey="Eidelberg D" first="David" last="Eidelberg">David Eidelberg</name>
<affiliation><nlm:aff id="A1">The Feinstein Institute for Medical Research, Manhasset, NY 11030</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of neuroscience : the official journal of the Society for Neuroscience</title>
<idno type="ISSN">0270-6474</idno>
<idno type="eISSN">1529-2401</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">We compared the metabolic and neurovascular effects of levodopa (LD) therapy for Parkinson’s disease (PD). Eleven PD patients were scanned with both [<sup>15</sup>
O]-H<sub>2</sub>
O and [<sup>18</sup>
F]-FDG PET in the unmedicated state and during intravenous LD infusion. Images were used to quantify LD-mediated changes in the expression of motor- and cognition-related PD covariance patterns in scans of cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMR). These changes in network activity were compared with those occurring during subthalamic nucleus deep brain stimulation (STN DBS), and those observed in a test-retest PD control group. Separate voxel-based searches were conducted to identify individual regions with dissociated treatment-mediated changes in local cerebral blood flow and metabolism.</p>
<p id="P2">We found a significant dissociation between CBF and CMR in the modulation of the PD motor-related network by LD treatment (p<0.001). This dissociation was characterized by reductions in network activity in the CMR scans (p<0.003) occurring concurrently with increases in the CBF scans (p<0.01). Flow-metabolism dissociation was also evident at the regional level, with LD-mediated reductions in CMR and increases in CBF in the putamen/globus pallidus, dorsal midbrain/pons, STN, and ventral thalamus. CBF responses to LD in the putamen and pons were relatively greater in patients exhibiting drug- induced dyskinesia. By contrast, flow-metabolism dissociation was not present in the STN DBS treatment group or in the PD control group. These findings suggest that flow-metabolism dissociation is a distinctive feature of LD treatment. This phenomenon may be especially pronounced in patients with LD-induced dyskinesia.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8102140</journal-id>
<journal-id journal-id-type="pubmed-jr-id">5035</journal-id>
<journal-id journal-id-type="nlm-ta">J Neurosci</journal-id>
<journal-title>The Journal of neuroscience : the official journal of the Society for Neuroscience</journal-title>
<issn pub-type="ppub">0270-6474</issn>
<issn pub-type="epub">1529-2401</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18417699</article-id>
<article-id pub-id-type="pmc">2577921</article-id>
<article-id pub-id-type="doi">10.1523/JNEUROSCI.0582-08.2008</article-id>
<article-id pub-id-type="manuscript">NIHMS60589</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson’s Disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hirano</surname>
<given-names>Shigeki</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Asanuma</surname>
<given-names>Kotaro</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Yilong</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tang</surname>
<given-names>Chengke</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Feigin</surname>
<given-names>Andrew</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dhawan</surname>
<given-names>Vijay</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Carbon</surname>
<given-names>Maren</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Eidelberg</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
The Feinstein Institute for Medical Research, Manhasset, NY 11030</aff>
<aff id="A2"><label>2</label>
Department of Neurology, Tokushima University Hospital Tokushima-City, Japan 770-8503</aff>
<aff id="A3"><label>3</label>
Departments of Neurology and Medicine, North Shore University Hospital and New York University School of Medicine, New York, New York</aff>
<author-notes><corresp id="CR1"><bold>Address Corresponding To:</bold>
David Eidelberg, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, Phone: (516) 562-2498; Fax: (516) 562-1008; E-mail: <email>david1@nshs.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>13</day>
<month>8</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="ppub"><day>16</day>
<month>4</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>4</day>
<month>11</month>
<year>2008</year>
</pub-date>
<volume>28</volume>
<issue>16</issue>
<fpage>4201</fpage>
<lpage>4209</lpage>
<abstract><p id="P1">We compared the metabolic and neurovascular effects of levodopa (LD) therapy for Parkinson’s disease (PD). Eleven PD patients were scanned with both [<sup>15</sup>
O]-H<sub>2</sub>
O and [<sup>18</sup>
F]-FDG PET in the unmedicated state and during intravenous LD infusion. Images were used to quantify LD-mediated changes in the expression of motor- and cognition-related PD covariance patterns in scans of cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMR). These changes in network activity were compared with those occurring during subthalamic nucleus deep brain stimulation (STN DBS), and those observed in a test-retest PD control group. Separate voxel-based searches were conducted to identify individual regions with dissociated treatment-mediated changes in local cerebral blood flow and metabolism.</p>
<p id="P2">We found a significant dissociation between CBF and CMR in the modulation of the PD motor-related network by LD treatment (p<0.001). This dissociation was characterized by reductions in network activity in the CMR scans (p<0.003) occurring concurrently with increases in the CBF scans (p<0.01). Flow-metabolism dissociation was also evident at the regional level, with LD-mediated reductions in CMR and increases in CBF in the putamen/globus pallidus, dorsal midbrain/pons, STN, and ventral thalamus. CBF responses to LD in the putamen and pons were relatively greater in patients exhibiting drug- induced dyskinesia. By contrast, flow-metabolism dissociation was not present in the STN DBS treatment group or in the PD control group. These findings suggest that flow-metabolism dissociation is a distinctive feature of LD treatment. This phenomenon may be especially pronounced in patients with LD-induced dyskinesia.</p>
</abstract>
<kwd-group><kwd>Parkinson’s disease</kwd>
<kwd>positron emission tomography</kwd>
<kwd>glucose metabolism</kwd>
<kwd>cerebral blood flow</kwd>
<kwd>levodopa treatment</kwd>
<kwd>STN DBS</kwd>
</kwd-group>
<contract-num rid="NS1">R01 NS035069-08</contract-num>
<contract-num rid="NS1">R01 NS035069-07</contract-num>
<contract-num rid="NS1">R01 NS035069-06</contract-num>
<contract-num rid="NS1">R01 NS035069-05A1</contract-num>
<contract-num rid="NS1">R01 NS035069-04</contract-num>
<contract-num rid="RR1">M01 RR018535-056239</contract-num>
<contract-num rid="RR1">M01 RR018535-047117</contract-num>
<contract-num rid="RR1">M01 RR018535-030004</contract-num>
<contract-num rid="RR1">M01 RR018535-020004</contract-num>
<contract-sponsor id="NS1">National Institute of Neurological Disorders and Stroke : NINDS</contract-sponsor>
<contract-sponsor id="RR1">National Center for Research Resources : NCRR</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
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