title: Dopaminergic correlates of metabolic network activity in Parkinson's disease.
abstract: Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P < 0.001), while PDCP expression correlated with uptake in the anterior striatum (P < 0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss.
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, 11030.
authors.forename: Florian
authors.initials: F
authors.lastname: Holtbernd
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, 11030.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, 11030.
authors.forename: Shichun
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schwartz
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Timmermann
authors.affiliation: Max-Planck Institute for Neurological Research, Cologne, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Kracht
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany.|Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Jülich Research Center, Jülich, Germany.
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, 11030.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Tang
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, 11030.
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany.|Max-Planck Institute for Neurological Research, Cologne, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Eggers
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007980:Levodopa; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D007980:Levodopa; D004298:Dopamine
keywords: FDOPA; PET; Parkinson's disease; brain networks; dopamine