High-frequency microstimulation in human globus pallidus and substantia nigra
Identifieur interne : 001D08 ( Main/Exploration ); précédent : 001D07; suivant : 001D09High-frequency microstimulation in human globus pallidus and substantia nigra
Auteurs : Myriam Lafreniere-Roula [Canada] ; Elaine Kim [Canada] ; William D. Hutchison [Canada] ; Andres M. Lozano [Canada] ; Mojgan Hodaie [Canada] ; Jonathan O. Dostrovsky [Canada]Source :
- Experimental brain research [ 0014-4819 ] ; 2010.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
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Abstract
Deep brain stimulation of the basal ganglia and other brain regions has been used successfully to treat a variety of neurological disorders. However, the mechanisms by which it works, remain unclear. In a previous study, we showed that locally delivered single current pulses delivered from a nearby microelectrode are sufficient to inhibit firing in the internal globus pallidus for tens of milliseconds. The GPi and the substantia nigra pars reticulata are the output nuclei of the basal ganglia and share many anatomical and physiological features. The goal of the current study was to examine the after-effects of trains of high-frequency microstimulation on neuronal firing in the GPi of Parkinson's disease and dystonia patients as well as in the SNr ofPD patients. Microelectrode recordings and microstimulation were performed in a total of 57 patients during stereotactic surgery. We found that firing in the GPi and SNr is inhibited for several hundreds of milliseconds following the end of a short, 200 Hz high-frequency train delivered through the recording electrode (e.g., on average 618 ms when stimulating in the SNr with a 0.5 s train of 4 μA pulses at 200 Hz). Inhibition duration usually increased with increasing current intensity, train frequency and generally peaked for trains of 1-2 s, while it decreased with increasing train durations. Statistical analysis with general linear models revealed a significant linear relationship between current intensity and inhibition duration in all nuclei and patient groups. There was also a significant relationship between train frequency and inhibition duration in the SNr and GPi of PD patients and between train duration and inhibition duration in the GPi of PD patients. There was no significant difference in inhibition duration across patient groups but the current threshold for inhibition was significantly different in the SNr compared to the GPi. The characteristics of the inhibition observed are consistent with stimulation-induced GABA release following activation of the GABAergic afferents in the SNr and GPi. The findings suggest that high-frequency microstimulation of the GPi and SNr depresses local neuronal activity and synaptic transmission, and such mechanisms may contribute to the therapeutic effects of DBS.
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Hutchison</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Physiology, University of Toronto, Medical Sciences Building Room 3302, 1 King's College Circle</s1><s2>Toronto, ON M5S 1A8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON M5S 1A8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Toronto Western Research Institute</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Toronto Western Hospital, Division of Neurosurgery, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Toronto Western Research Institute</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Hodaie, Mojgan" sort="Hodaie, Mojgan" uniqKey="Hodaie M" first="Mojgan" last="Hodaie">Mojgan Hodaie</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Toronto Western Research Institute</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Toronto Western Hospital, Division of Neurosurgery, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Dostrovsky, Jonathan O" sort="Dostrovsky, Jonathan O" uniqKey="Dostrovsky J" first="Jonathan O." last="Dostrovsky">Jonathan O. Dostrovsky</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Physiology, University of Toronto, Medical Sciences Building Room 3302, 1 King's College Circle</s1><s2>Toronto, ON M5S 1A8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON M5S 1A8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Toronto Western Research Institute</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Research Institute</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Experimental brain research</title><title level="j" type="abbreviated">Exp. brain res.</title><idno type="ISSN">0014-4819</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Experimental brain research</title><title level="j" type="abbreviated">Exp. brain res.</title><idno type="ISSN">0014-4819</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>After effect</term><term>Basal ganglion</term><term>Deep brain stimulation</term><term>Dystonia</term><term>Encephalon</term><term>GABA</term><term>Human</term><term>Locus niger</term><term>Parkinson disease</term><term>Release</term><term>Statistical analysis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Locus niger</term><term>Encéphale</term><term>Noyau gris central</term><term>Effet consécutif</term><term>Dystonie</term><term>Analyse statistique</term><term>GABA</term><term>Libération</term><term>Maladie de Parkinson</term><term>Homme</term><term>Stimulation cérébrale profonde</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deep brain stimulation of the basal ganglia and other brain regions has been used successfully to treat a variety of neurological disorders. However, the mechanisms by which it works, remain unclear. In a previous study, we showed that locally delivered single current pulses delivered from a nearby microelectrode are sufficient to inhibit firing in the internal globus pallidus for tens of milliseconds. The GPi and the substantia nigra pars reticulata are the output nuclei of the basal ganglia and share many anatomical and physiological features. The goal of the current study was to examine the after-effects of trains of high-frequency microstimulation on neuronal firing in the GPi of Parkinson's disease and dystonia patients as well as in the SNr ofPD patients. Microelectrode recordings and microstimulation were performed in a total of 57 patients during stereotactic surgery. We found that firing in the GPi and SNr is inhibited for several hundreds of milliseconds following the end of a short, 200 Hz high-frequency train delivered through the recording electrode (e.g., on average 618 ms when stimulating in the SNr with a 0.5 s train of 4 μA pulses at 200 Hz). Inhibition duration usually increased with increasing current intensity, train frequency and generally peaked for trains of 1-2 s, while it decreased with increasing train durations. Statistical analysis with general linear models revealed a significant linear relationship between current intensity and inhibition duration in all nuclei and patient groups. There was also a significant relationship between train frequency and inhibition duration in the SNr and GPi of PD patients and between train duration and inhibition duration in the GPi of PD patients. There was no significant difference in inhibition duration across patient groups but the current threshold for inhibition was significantly different in the SNr compared to the GPi. The characteristics of the inhibition observed are consistent with stimulation-induced GABA release following activation of the GABAergic afferents in the SNr and GPi. The findings suggest that high-frequency microstimulation of the GPi and SNr depresses local neuronal activity and synaptic transmission, and such mechanisms may contribute to the therapeutic effects of DBS.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Lafreniere Roula, Myriam" sort="Lafreniere Roula, Myriam" uniqKey="Lafreniere Roula M" first="Myriam" last="Lafreniere-Roula">Myriam Lafreniere-Roula</name></region><name sortKey="Dostrovsky, Jonathan O" sort="Dostrovsky, Jonathan O" uniqKey="Dostrovsky J" first="Jonathan O." last="Dostrovsky">Jonathan O. Dostrovsky</name><name sortKey="Dostrovsky, Jonathan O" sort="Dostrovsky, Jonathan O" uniqKey="Dostrovsky J" first="Jonathan O." last="Dostrovsky">Jonathan O. Dostrovsky</name><name sortKey="Hodaie, Mojgan" sort="Hodaie, Mojgan" uniqKey="Hodaie M" first="Mojgan" last="Hodaie">Mojgan Hodaie</name><name sortKey="Hodaie, Mojgan" sort="Hodaie, Mojgan" uniqKey="Hodaie M" first="Mojgan" last="Hodaie">Mojgan Hodaie</name><name sortKey="Hutchison, William D" sort="Hutchison, William D" uniqKey="Hutchison W" first="William D." last="Hutchison">William D. Hutchison</name><name sortKey="Hutchison, William D" sort="Hutchison, William D" uniqKey="Hutchison W" first="William D." last="Hutchison">William D. Hutchison</name><name sortKey="Hutchison, William D" sort="Hutchison, William D" uniqKey="Hutchison W" first="William D." last="Hutchison">William D. Hutchison</name><name sortKey="Kim, Elaine" sort="Kim, Elaine" uniqKey="Kim E" first="Elaine" last="Kim">Elaine Kim</name><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. 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