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.

Assessing the Effects of Continuous Theta Burst Stimulation Over the Dorsolateral Prefrontal Cortex on Human Cognition: A Systematic Review

“…The implication of the DLPFC in major depression (Lemogne et al, 2010 ; Sibille et al, 2011 ) has made it a key target in treatment intervention. It is also important to note that the DLPFC has been strongly associated with basic executive functions, such as working memory and attentional and inhibitory control as well as higher level EF processes, such as planning and intelligence (fluid intelligence) (Miller and Cohen, 2001 ; Wood and Grafman, 2003 ; Forbes et al, 2014 ; Snyder, 2014 ; Caspers et al, 2017 ). This implies that there is a close interlink between the dysfunction of executive function and major depression, and it is also possible that MDD is a product of a serious cognitive breakdown.…”

Increased functional connectivity of thalamic subdivisions in patients with Parkinson’s disease

“…Our findings of increased FC between the MD/A thalamus and the dorsolateral prefrontal cortex may represent functional compensatory mechanisms due to the significant cognitive dysfunction common in PD. The dorsolateral prefrontal cortex helps to execute tasks that contribute to cognitive functioning, including working memory, decision-making and action control, achieved through a top-down modulation of behavior in concert with diverse cortical and subcortical structures [61]. Research has shown that FC is significantly increased across the prefrontal cortex in PD subjects on medication, as the brain potentially recruits new anatomical areas to aid in the performance of cognitive tasks.…”

Low-Frequency Repetitive Transcranial Magnetic Stimulation over Right Dorsolateral Prefrontal Cortex in Parkinson’s Disease

“…High-frequency rTMS over left DLPFC, with comparable effects to those of antidepressants [ 13 ], was proved beneficial in treating PD-related depression in several studies [ 7 , 14 , 15 ]. Studies targeting the right DLPFC were largely based on its role of executive function such as working memory, decision making, and coping with novel tasks [ 8 ], which were found to be impaired at the early stage of PD [ 16 ]. Unilateral right DLPFC stimulation was shown to have a positive effect for individuals with PD on timed up-and-go task performance [ 17 ], spatial planning [ 18 ], metaphor comprehension [ 19 ], and time perception [ 20 ] via rTMS or other brain stimulation tools.…”

“…Among the targets, the right dorsolateral prefrontal cortex (DLPFC) has been applied to alleviate PD-related depression using low-frequency rTMS based on the rationale of imbalanced interregional activity (overactive right DLPFC and underactive left DLPFC) [ 7 ]. Besides, right DLPFC plays a crucial role in executive function [ 8 ] which may be reflected in cognitive change and motor-related dysfunction such as speech or limb movement in PD [ 8 , 9 ]. Sleep disturbance, one common nonmotor symptom of PD, was also suggested to benefit from low-frequency rTMS over DLPFC [ 10 ].…”