Dataset Information

Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease.

ABSTRACT: Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF) like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC) has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC) in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF) and under their regular dopaminergic medication (ON). We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC) and left dorsal premotor region (PMd) in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC) in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part.

SUBMITTER: Caspers J

PROVIDER: S-EPMC5447710 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease.

Caspers Julian J Mathys Christian C Hoffstaedter Felix F Südmeyer Martin M Cieslik Edna C EC Rubbert Christian C Hartmann Christian J CJ Eickhoff Claudia R CR Reetz Kathrin K Grefkes Christian C Michely Jochen J Turowski Bernd B Schnitzler Alfons A Eickhoff Simon B SB

Frontiers in human neuroscience 20170530

Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF) like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC) has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engag ...[more]

PMID: 28611616

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Project description:The pathological hallmark of Parkinson's disease is the degeneration of dopaminergic nigrostriatal neurons, leading to depletion of striatal dopamine. Recent neuroanatomical work has identified pathways for communication across striatal subdivisions, suggesting that the striatum provides a platform for integration of information across parallel corticostriatal circuits. The aim of this study was to investigate whether dopaminergic dysfunction in Parkinson's disease was associated with impairments in functional connectivity across striatal subdivisions, which could potentially reflect reduced integration across corticostriatal circuits. Utilizing resting-state functional magnetic resonance imaging (fMRI), we analyzed functional connectivity in 39 patients with Parkinson's disease, both "on" and "off" their regular dopaminergic medications, along with 40 age-matched healthy controls. Our results demonstrate widespread impairments in connectivity across subdivisions of the striatum in patients with Parkinson's disease in the "off" state. The administration of dopaminergic medication significantly improved connectivity across striatal subdivisions in Parkinson's disease, implicating dopaminergic deficits in the pathogenesis of impaired striatal interconnectivity. In addition, impaired striatal interconnectivity in the Parkinson's disease "off" state was associated with pathological decoupling of the striatum from the thalamic and sensorimotor (SM) networks. Specifically, we found that although the strength of striatal interconnectivity was positively correlated with both (i) the strength of internal thalamic connectivity, and (ii) the strength of internal SM connectivity, in both healthy controls and the Parkinson's disease "on" state, these relationships were absent in Parkinson's disease when in the "off" state. Taken together our findings emphasize the central role of dopamine in integrated striatal function and the pathological consequences of striatal dopamine denervation in Parkinson's disease.

Project description:Since anatomic MRI is presently not able to directly discern neuronal loss in Parkinson's Disease (PD), studying the associated functional connectivity (FC) changes seems a promising approach toward developing non-invasive and non-radioactive neuroimaging markers for this disease. While several groups have reported such FC changes in PD, there are also significant discrepancies between studies. Investigating the reproducibility of PD-related FC changes on independent datasets is therefore of crucial importance. We acquired resting-state fMRI scans for 43 subjects (27 patients and 16 normal controls, with 2 replicate scans per subject) and compared the observed FC changes with those obtained in two independent datasets, one made available by the PPMI consortium (91 patients, 18 controls) and a second one by the group of Tao Wu (20 patients, 20 controls). Unfortunately, PD-related functional connectivity changes turned out to be non-reproducible across datasets. This could be due to disease heterogeneity, but also to technical differences. To distinguish between the two, we devised a method to directly check for disease heterogeneity using random splits of a single dataset. Since we still observe non-reproducibility in a large fraction of random splits of the same dataset, we conclude that functional heterogeneity may be a dominating factor behind the lack of reproducibility of FC alterations in different rs-fMRI studies of PD. While global PD-related functional connectivity changes were non-reproducible across datasets, we identified a few individual brain region pairs with marginally consistent FC changes across all three datasets. However, training classifiers on each one of the three datasets to discriminate PD scans from controls produced only low accuracies on the remaining two test datasets. Moreover, classifiers trained and tested on random splits of the same dataset (which are technically homogeneous) also had low test accuracies, directly substantiating disease heterogeneity.

Dataset Information

Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease.

Publications

Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease.

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