Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.
Identifieur interne : 000853 ( PubMed/Corpus ); précédent : 000852; suivant : 000854Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.
Auteurs : Mark D. Humphries ; Kevin GurneySource :
- The European journal of neuroscience [ 1460-9568 ] ; 2012.
English descriptors
- KwdEn :
- Animals, Basal Ganglia (physiology), Brain Waves (physiology), Deep Brain Stimulation, Evoked Potentials (physiology), Models, Neurological, Nerve Net (physiology), Parkinson Disease (physiopathology), Parkinson Disease (therapy), Rats, Subthalamic Nucleus (physiology), Synaptic Transmission (physiology).
- MESH :
- physiology : Basal Ganglia, Brain Waves, Evoked Potentials, Nerve Net, Subthalamic Nucleus, Synaptic Transmission.
- physiopathology : Parkinson Disease.
- therapy : Parkinson Disease.
- Animals, Deep Brain Stimulation, Models, Neurological, Rats.
Abstract
Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS.
DOI: 10.1111/j.1460-9568.2012.08085.x
PubMed: 22805068
Links to Exploration step
pubmed:22805068Le document en format XML
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Humphries</name><affiliation><nlm:affiliation>Group for Neural Theory, Department d'Etudes Cognitives, Ecole Normale Superieure, 29 rue d'Ulm, 75005 Paris, France. m.d.humphries@shef.ac.uk</nlm:affiliation></affiliation></author><author><name sortKey="Gurney, Kevin" sort="Gurney, Kevin" uniqKey="Gurney K" first="Kevin" last="Gurney">Kevin Gurney</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="RBID">pubmed:22805068</idno><idno type="pmid">22805068</idno><idno type="doi">10.1111/j.1460-9568.2012.08085.x</idno><idno type="wicri:Area/PubMed/Corpus">000853</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000853</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.</title><author><name sortKey="Humphries, Mark D" sort="Humphries, Mark D" uniqKey="Humphries M" first="Mark D" last="Humphries">Mark D. Humphries</name><affiliation><nlm:affiliation>Group for Neural Theory, Department d'Etudes Cognitives, Ecole Normale Superieure, 29 rue d'Ulm, 75005 Paris, France. m.d.humphries@shef.ac.uk</nlm:affiliation></affiliation></author><author><name sortKey="Gurney, Kevin" sort="Gurney, Kevin" uniqKey="Gurney K" first="Kevin" last="Gurney">Kevin Gurney</name></author></analytic><series><title level="j">The European journal of neuroscience</title><idno type="eISSN">1460-9568</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Basal Ganglia (physiology)</term><term>Brain Waves (physiology)</term><term>Deep Brain Stimulation</term><term>Evoked Potentials (physiology)</term><term>Models, Neurological</term><term>Nerve Net (physiology)</term><term>Parkinson Disease (physiopathology)</term><term>Parkinson Disease (therapy)</term><term>Rats</term><term>Subthalamic Nucleus (physiology)</term><term>Synaptic Transmission (physiology)</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Basal Ganglia</term><term>Brain Waves</term><term>Evoked Potentials</term><term>Nerve Net</term><term>Subthalamic Nucleus</term><term>Synaptic Transmission</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Deep Brain Stimulation</term><term>Models, Neurological</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22805068</PMID><DateCreated><Year>2012</Year><Month>07</Month><Day>18</Day></DateCreated><DateCompleted><Year>2012</Year><Month>11</Month><Day>12</Day></DateCompleted><DateRevised><Year>2012</Year><Month>07</Month><Day>18</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1460-9568</ISSN><JournalIssue CitedMedium="Internet"><Volume>36</Volume><Issue>2</Issue><PubDate><Year>2012</Year><Month>Jul</Month></PubDate></JournalIssue><Title>The European journal of neuroscience</Title><ISOAbbreviation>Eur. J. Neurosci.</ISOAbbreviation></Journal><ArticleTitle>Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.</ArticleTitle><Pagination><MedlinePgn>2240-51</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/j.1460-9568.2012.08085.x</ELocationID><Abstract><AbstractText>Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS.</AbstractText><CopyrightInformation>© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Humphries</LastName><ForeName>Mark D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Group for Neural Theory, Department d'Etudes Cognitives, Ecole Normale Superieure, 29 rue d'Ulm, 75005 Paris, France. m.d.humphries@shef.ac.uk</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gurney</LastName><ForeName>Kevin</ForeName><Initials>K</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Eur J Neurosci</MedlineTA><NlmUniqueID>8918110</NlmUniqueID><ISSNLinking>0953-816X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001479" MajorTopicYN="N">Basal Ganglia</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058256" MajorTopicYN="N">Brain Waves</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D046690" MajorTopicYN="Y">Deep Brain Stimulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005071" MajorTopicYN="N">Evoked Potentials</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008959" MajorTopicYN="Y">Models, Neurological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009415" MajorTopicYN="N">Nerve Net</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020531" MajorTopicYN="N">Subthalamic Nucleus</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009435" MajorTopicYN="N">Synaptic Transmission</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>7</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>7</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22805068</ArticleId><ArticleId IdType="doi">10.1111/j.1460-9568.2012.08085.x</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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