Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/92619
DC FieldValueLanguage
dc.contributor.authorRebelo, Diliana-
dc.contributor.authorOliveira, Francisco-
dc.contributor.authorAbrunhosa, Antero-
dc.contributor.authorJanuário, Cristina-
dc.contributor.authorLemos, João-
dc.contributor.authorCastelo-Branco, Miguel-
dc.date.accessioned2021-01-20T15:34:47Z-
dc.date.available2021-01-20T15:34:47Z-
dc.date.issued2021-01-19-
dc.identifier.issn0027-8424pt
dc.identifier.issn1091-6490pt
dc.identifier.urihttp://hdl.handle.net/10316/92619-
dc.description.abstractThe link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D2 receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D2 receptors (using 11C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D2 binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD.pt
dc.language.isoengpt
dc.publisherNational Academy of Sciencespt
dc.relationFCT/UID/4950/201pt
dc.relationPAC/MEDPERSYST-16428pt
dc.relationCENTRO-01-0145-FEDER-000016pt
dc.relationBial Foundation 252/18pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectFunctional connectivitypt
dc.subjectFunctional magnetic resonance imagingpt
dc.subject.meshMolecular imagingpt
dc.subject.meshPositron emission tomographypt
dc.titleA link between synaptic plasticity and reorganization of brain activity in Parkinson's diseasept
dc.typearticle-
degois.publication.firstPagee2013962118pt
degois.publication.issue3pt
degois.publication.titlePNAS - Proceedings of the National Academy of Sciences of the United States of Americapt
dc.relation.publisherversionhttps://www.pnas.org/content/118/3/e2013962118pt
dc.peerreviewedyespt
dc.identifier.doi10.1073/pnas.2013962118pt
degois.publication.volume118pt
dc.date.embargo2021-01-19*
uc.date.periodoEmbargo0pt
item.grantfulltextopen-
item.languageiso639-1en-
item.fulltextCom Texto completo-
crisitem.author.deptFaculty of Medicine-
crisitem.author.deptFaculty of Medicine-
crisitem.author.deptFaculty of Medicine-
crisitem.author.deptFaculty of Medicine-
crisitem.author.deptFaculty of Medicine-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCIBIT - Coimbra Institute for Biomedical Imaging and Translational Research-
crisitem.author.orcid0000-0003-0279-0221-
crisitem.author.orcid0000-0001-9468-8894-
crisitem.author.orcid0000-0002-4145-854X-
crisitem.author.orcid0000-0001-5402-3978-
crisitem.author.orcid0000-0002-9128-7064-
crisitem.author.orcid0000-0003-4364-6373-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
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