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.
Highlights
Parkinson’s disease (PD) is predominantly determined by motor symptoms, cognitive deficits are increasingly recognized as key features of the disorder, having profound impact on patient’s quality of life (Michely et al, 2012; SantosGarcia and de la Fuente-Fernandez, 2013; Berganzo et al, 2014)
We found significantly reduced functional connectivity (FC) for the posterior right dorsolateral prefrontal cortex (dlPFC) seed in PD patients in the medical OFF condition compared to healthy controls with bilateral posterior parietal and left premotor regions (Figure 2, Table 3)
From the two seed regions within the right dlPFC involved in cognitive action control, only the posterior subdivision features distinct FC changes in PD
Summary
Parkinson’s disease (PD) is predominantly determined by motor symptoms, cognitive deficits are increasingly recognized as key features of the disorder, having profound impact on patient’s quality of life (Michely et al, 2012; SantosGarcia and de la Fuente-Fernandez, 2013; Berganzo et al, 2014). Affection of cognitive abilities in PD has mainly been attributed to disturbance of frontostriatal circuits caused by dopaminergic depletion (Owen, 2004; Leh et al, 2010). In this regard, the prefrontal cortex, and the dorsolateral prefrontal cortex (dlPFC) in particular, have been repeatedly reported by neuroimaging studies to show alterations in their function and connectivity in PD (e.g., Cools et al, 2002; Lewis et al, 2003; Monchi et al, 2007; Hirano et al, 2012; Disbrow et al, 2013). It could be demonstrated that deficits in EF tests are a predictor for the development of dementia in PD (Levy et al, 2002; Janvin et al, 2005)
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