Abstract
The cholinergic system arising from the basal forebrain plays an important role in cognitive performance in Parkinson’s disease (PD). Here, we analyzed cholinergic status-dependent cortical and subcortical resting-state functional connectivity in PD. A total of 61 drug-naïve PD patients were divided into tertiles based on normalized substantia innominata (SI) volumes. We compared the resting-state network from seed region of interest in the caudate, posterior cingulate cortex (PCC), and SI between the lowest (PD-L) and highest tertile (PD-H) groups. Correlation analysis of the functional networks was also performed in all subjects. The functional network analysis showed that PD-L subjects displayed decreased striato-cortical functional connectivity compared with PD-H subjects. Selecting the PCC as a seed, the PD-L patients displayed decreased functional connectivity compared to PD-H patients. Meanwhile, PD-L subjects had significantly increased cortical functional connectivity with the SI compared with PD-H subjects. Correlation analysis revealed that SI volume had a positive correlation with functional connectivity from the right caudate and PCC. The present study demonstrated that PD patients exhibited unique functional connectivity from the caudate and the PCC that may be closely associated with cholinergic status, suggesting an important role for the cholinergic system in PD-associated cognition.
Highlights
Cognitive impairment, as one of the most disabling non-motor features, is known to occur in the early stages of PD1
When the right caudate nucleus was selected as a seed, Parkinson’s disease (PD)-H showed decreased functional connectivity compared with controls in the frontal areas, parietal area, temporal areas, precentral area, posterior cingulate area, and cerebellar areas (Fig. 1A)
Using the left caudate as a seed for the Resting-state networks (RSN) analysis, PD-H exhibited decreased striato-cortical functional connectivity compared with normal controls in the postcentral area, parietal area, prefrontal and anterior cingulate areas, temporal areas, fusiform areas, and cerebellar areas (Supplementary Fig. 1A)
Summary
As one of the most disabling non-motor features, is known to occur in the early stages of PD1. A recent in vivo positron emission tomography (PET) study of cerebral acetylcholinesterase demonstrated that cholinergic dysfunction occurs in the early course of PD and is more widespread and profound in the development of PDD3,4. Resting-state networks (RSN) are associated with self-oriented mental activity and offer a means of evaluating the status of functional systems within the brain without externally goal-directed cognitive performance[7]. RSN analysis may be helpful in the identification of brain regions functionally coupled with pathological change-dependent processes in neurodegenerative disease. We performed a comparative analysis of RSN according to the SI volume in non-demented drug naïve PD patients to further elucidate cholinergic system-dependent cortical-subcortical functional networks
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