Computational Dissection of Dopamine Motor and Motivational Functions in Humans.
Identifieur interne : 000321 ( Main/Exploration ); précédent : 000320; suivant : 000322Computational Dissection of Dopamine Motor and Motivational Functions in Humans.
Auteurs : Raphaël Le Bouc ; Lionel Rigoux ; Liane Schmidt [France] ; Bertrand Degos [France] ; Marie-Laure Welter [France] ; Marie Vidailhet [France] ; Jean Daunizeau ; Mathias Pessiglione [Oman]Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience [ 1529-2401 ] ; 2016.
Abstract
Motor dysfunction (e.g., bradykinesia) and motivational deficit (i.e., apathy) are hallmarks of Parkinson's disease (PD). Yet, it remains unclear whether these two symptoms arise from a same dopaminergic dysfunction. Here, we develop a computational model that articulates motor control to economic decision theory, to dissect the motor and motivational functions of dopamine in humans. This model can capture different aspects of the behavior: choice (which action is selected) and vigor (action speed and intensity). It was used to characterize the behavior of 24 PD patients, tested both when medicated and unmedicated, in two behavioral tasks: an incentive motivation task that involved producing a physical effort, knowing that it would be multiplied by reward level to calculate the payoff, and a binary choice task that involved choosing between high reward/high effort and low reward/low effort options. Model-free analyses in both tasks showed the same two effects when comparing unmedicated patients to medicated patients: dopamine depletion (1) decreased the amount of effort that patients were willing to produce for a given reward and (2) slowed down the production of this effort, regardless of reward level. Model-based analyses captured these effects with two independent parameters, namely reward sensitivity and motor activation rate. These two parameters were respectively predictive of medication effects on clinical measures of apathy and motor dysfunction. More generally, we suggest that such computational phenotyping might help characterizing deficits and refining treatments in neuropsychiatric disorders.
DOI: 10.1523/JNEUROSCI.3078-15.2016
PubMed: 27335396
Affiliations:
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type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Daunizeau, Jean" sort="Daunizeau, Jean" uniqKey="Daunizeau J" first="Jean" last="Daunizeau">Jean Daunizeau</name><affiliation><nlm:affiliation>Motivation, Brain and Behavior Team, Institut du cerveau et de la Moelle Epinière, INSERM UMR1127, CNRS UMR 7225, Université Pierre et Marie Curie-Paris 6.</nlm:affiliation><wicri:noCountry code="subField">Université Pierre et Marie Curie-Paris 6</wicri:noCountry></affiliation></author><author><name sortKey="Pessiglione, Mathias" sort="Pessiglione, Mathias" uniqKey="Pessiglione M" first="Mathias" last="Pessiglione">Mathias Pessiglione</name><affiliation wicri:level="1"><nlm:affiliation>Motivation, Brain and Behavior Team, Institut du cerveau et de la Moelle Epinière, INSERM UMR1127, CNRS UMR 7225, Université Pierre et Marie Curie-Paris 6, mathias.pessiglione@gmail.com.</nlm:affiliation><country wicri:rule="url">Oman</country><wicri:regionArea>Motivation, Brain and Behavior Team, Institut du cerveau et de la Moelle Epinière, INSERM UMR1127, CNRS UMR 7225, Université Pierre et Marie Curie-Paris 6</wicri:regionArea><wicri:noRegion>Université Pierre et Marie Curie-Paris 6</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of neuroscience : the official journal of the Society for Neuroscience</title><idno type="eISSN">1529-2401</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Motor dysfunction (e.g., bradykinesia) and motivational deficit (i.e., apathy) are hallmarks of Parkinson's disease (PD). Yet, it remains unclear whether these two symptoms arise from a same dopaminergic dysfunction. Here, we develop a computational model that articulates motor control to economic decision theory, to dissect the motor and motivational functions of dopamine in humans. This model can capture different aspects of the behavior: choice (which action is selected) and vigor (action speed and intensity). It was used to characterize the behavior of 24 PD patients, tested both when medicated and unmedicated, in two behavioral tasks: an incentive motivation task that involved producing a physical effort, knowing that it would be multiplied by reward level to calculate the payoff, and a binary choice task that involved choosing between high reward/high effort and low reward/low effort options. Model-free analyses in both tasks showed the same two effects when comparing unmedicated patients to medicated patients: dopamine depletion (1) decreased the amount of effort that patients were willing to produce for a given reward and (2) slowed down the production of this effort, regardless of reward level. Model-based analyses captured these effects with two independent parameters, namely reward sensitivity and motor activation rate. These two parameters were respectively predictive of medication effects on clinical measures of apathy and motor dysfunction. More generally, we suggest that such computational phenotyping might help characterizing deficits and refining treatments in neuropsychiatric disorders.</div></front></TEI><affiliations><list><country><li>France</li><li>Oman</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Daunizeau, Jean" sort="Daunizeau, Jean" uniqKey="Daunizeau J" first="Jean" last="Daunizeau">Jean Daunizeau</name><name sortKey="Le Bouc, Raphael" sort="Le Bouc, Raphael" uniqKey="Le Bouc R" first="Raphaël" last="Le Bouc">Raphaël Le Bouc</name><name sortKey="Rigoux, Lionel" sort="Rigoux, Lionel" uniqKey="Rigoux L" first="Lionel" last="Rigoux">Lionel Rigoux</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Schmidt, Liane" sort="Schmidt, Liane" uniqKey="Schmidt L" first="Liane" last="Schmidt">Liane Schmidt</name></region><name sortKey="Degos, Bertrand" sort="Degos, Bertrand" uniqKey="Degos B" first="Bertrand" last="Degos">Bertrand Degos</name><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><name sortKey="Welter, Marie Laure" sort="Welter, Marie Laure" uniqKey="Welter M" first="Marie-Laure" last="Welter">Marie-Laure Welter</name></country><country name="Oman"><noRegion><name sortKey="Pessiglione, Mathias" sort="Pessiglione, Mathias" uniqKey="Pessiglione M" first="Mathias" last="Pessiglione">Mathias Pessiglione</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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