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Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson's disease

Li, Weihua ; Lao-Kaim, Nick P. ; Roussakis, Andreas Antonios ; Martín-Bastida, Antonio ; Valle-Guzman, Natalie ; Paul, Gesine LU ; Soreq, Eyal ; Daws, Richard E. ; Foltynie, Tom and Barker, Roger A. LU , et al. (2020) In NeuroImage: Clinical 28.
Abstract

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson's disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of... (More)

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson's disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11C-PE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. Results: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. Conclusions: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C-PE2I, Dopamine transporter, Functional connectivity, Parkinson's disease, Resting-state functional magnetic resonance imaging
in
NeuroImage: Clinical
volume
28
article number
102409
publisher
Elsevier
external identifiers
  • pmid:32916466
  • scopus:85090335034
ISSN
2213-1582
DOI
10.1016/j.nicl.2020.102409
language
English
LU publication?
yes
id
80b25f65-abd3-437c-90be-82f545253eeb
date added to LUP
2020-10-20 11:22:46
date last changed
2021-01-06 05:02:15
@article{80b25f65-abd3-437c-90be-82f545253eeb,
  abstract     = {<p>Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson's disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using <sup>11</sup>C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. <sup>11</sup>C-PE2I binding potential (BP<sub>ND</sub>) was calculated for each participant. PD patients were assessed for disease severity. Results: At baseline, PD patients with greater dopaminergic deficits, as measured with <sup>11</sup>C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. Conclusions: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression.</p>},
  author       = {Li, Weihua and Lao-Kaim, Nick P. and Roussakis, Andreas Antonios and Martín-Bastida, Antonio and Valle-Guzman, Natalie and Paul, Gesine and Soreq, Eyal and Daws, Richard E. and Foltynie, Tom and Barker, Roger A. and Hampshire, Adam and Piccini, Paola},
  issn         = {2213-1582},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {NeuroImage: Clinical},
  title        = {Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson's disease},
  url          = {http://dx.doi.org/10.1016/j.nicl.2020.102409},
  doi          = {10.1016/j.nicl.2020.102409},
  volume       = {28},
  year         = {2020},
}