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Title: A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease
Authors: Rebelo, Diliana 
Oliveira, Francisco 
Abrunhosa, Antero 
Januário, Cristina 
Lemos, João 
Castelo-Branco, Miguel 
Keywords: Functional connectivity; Functional magnetic resonance imaging
Issue Date: 19-Jan-2021
Publisher: National Academy of Sciences
Project: FCT/UID/4950/201 
Bial Foundation 252/18 
Serial title, monograph or event: PNAS - Proceedings of the National Academy of Sciences of the United States of America
Volume: 118
Issue: 3
Abstract: The 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.
ISSN: 0027-8424
DOI: 10.1073/pnas.2013962118
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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