In patients with Parkinson disease (PD), atrophic changes occur mainly in the limbic/paralimbic and prefrontal areas. These atrophic changes may be related to the development of dementia in PD.

We investigated the effect of transient dopamine depletion on functional connectivity during performance of the Wisconsin Card Sorting Task. Functional magnetic resonance imaging data were analyzed as a psychophysiological interaction, a statistical method used to identify functional connectivity during experimental manipulations. Nineteen healthy subjects were scanned, double blind, on 2 separate days: once after drinking an amino acid mixture deficient in the dopamine precursors tyrosine and phenylalanine, and once after drinking a nutritionally balanced mixture. In the balanced drink session, statistically significant connectivity between the frontal lobes and striatum was observed during set shifting, and the greater the prefrontostriatal connectivity, the faster the response time after a shift. Neither of these associations were observed after dopamine depletion. Moreover, dopamine depletion also reduced the degree of deactivation in areas normally suppressed during attention-demanding tasks, including the medial prefrontal cortex, posterior cingulate cortex, and hippocampus. Together, these results suggest that functional connectivity between the frontal lobes and basal ganglia during set shifting contributes to more efficient performance and that dopamine modulates this corticostriatal connectivity.

We investigated the relative differences in dopaminergic function through the whole brain in patients with Parkinson's disease without dementia (PD) and with dementia (PDD) using 6-[18F]fluoro-L-dopa (18F-dopa) PET and a voxel-by-voxel analysis. The 10 PD and 10 PDD patients were equivalently disabled, having mean scores of 3.2 +/- 0.6 and 3.2 +/- 0.7, respectively, on the Hoehn and Yahr rating scale. 18F-dopa influx constant (Ki) images of those patients and 15 normal age-matched subjects were transformed into standard stereotactic space. The significant differences between the groups (expressed in mean regional Ki values) were localized with statistical parametric mapping (SPM) on a voxel-by-voxel basis. Compared with the normal group, SPM localized declines of the 18F-dopa Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group (P < 0.01, corrected). Compared with the normal group, the PDD group showed reduced 18F-dopa Ki bilaterally in the striatum, midbrain and anterior cingulate area (P < 0.01, corrected). A relative difference in 18F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group (P < 0.001, corrected). Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function.

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The present study provides evidence of stress-induced dopamine release in the mPFC in humans, in vivo.

Dopaminergic projections are hypothesized to stabilize neural signaling and neural representations, but how they shape regional information processing and large-scale network interactions remains unclear. Here we investigated effects of lowered dopamine levels on within-region temporal signal variability (measured by sample entropy) and between-region functional connectivity (measured by pairwise temporal correlations) in the healthy brain at rest. The acute phenylalanine and tyrosine depletion (APTD) method was used to decrease dopamine synthesis in 51 healthy participants who underwent resting-state functional MRI (fMRI) scanning. Functional connectivity and regional signal variability were estimated for each participant. Multivariate partial least squares (PLS) analysis was used to statistically assess changes in signal variability following APTD as compared with the balanced control treatment. The analysis captured a pattern of increased regional signal variability following dopamine depletion. Changes in hemodynamic signal variability were concomitant with changes in functional connectivity, such that nodes with greatest increase in signal variability following dopamine depletion also experienced greatest decrease in functional connectivity. Our results suggest that dopamine may act to stabilize neural signaling, particularly in networks related to motor function and orienting attention towards behaviorally-relevant stimuli. Moreover, dopamine-dependent signal variability is critically associated with functional embedding of individual areas in large-scale networks.

To determine the characteristics of cerebral glucose metabolism in Parkinson's disease patients with visual hallucinations, group comparison studies using [18F]fluorodeoxyglucose positron emission tomography were performed. Nondemented Parkinson's disease patients in advanced stages were classified into two groups: (1) patients without visual hallucinations; (2) patients with visual hallucinations. Compared to patients without hallucinations, the relative regional cerebral glucose metabolic rate was greater in the frontal areas in patients with visual hallucinations, and the increase reached a significant level in the left superior frontal gyrus. Relative frontal hypermetabolism may be a feature of Parkinson's disease patients with visual hallucinations.