Altered Intra- and Inter-Network Connectivity in Drug-Naïve Patients With Early Parkinson's Disease.

Weiqi Zeng,Ziqin Cao,Yan Xu,Yu Xu,Xiaoman Yang,Ling Liu,Xiangchuang Kong,Xiaoming Liu,Xuebing Cao,Chi Cheng,Wenliang Fan,Xiaoqian Zhang,Yi Wu

doi:10.3389/fnagi.2022.783634

Abstract

The aim of our study was to investigate differences in whole brain connectivity at different levels between drug-naïve individuals with early Parkinson’s disease (PD) and healthy controls (HCs). Resting-state functional magnetic resonance imaging data were collected from 47 patients with early-stage, drug-naïve PD and 50 HCs. Functional brain connectivity was analyzed at the integrity, network, and edge levels; UPDRS-III, MMSE, MOCA, HAMA, and HAMD scores, reflecting the symptoms of PD, were collected for further regression analysis. Compared with age-matched HCs, reduced functional connectivity were mainly observed in the visual (VSN), somatomotor (SMN), limbic (LBN), and deep gray matter networks (DGN) at integrity level [p < 0.05, false discovery rate (FDR) corrected]. Intra-network analysis indicated decreased functional connectivity in DGN, SMN, LBN, and ventral attention networks (VAN). Inter-network analysis indicated reduced functional connectivity in nine pairs of resting-state networks. At the edge level, the LBN was the center of abnormal functional connectivity (p < 0.05, FDR corrected). MOCA score was associated with the intra-network functional connectivity strength (FC) of the DGN, and inter-network FC of the DGN-VAN. HAMA and HAMD scores were associated with the FC of the SMN and DGN, and either the LBN or VAN, respectively. We demonstrated variations in whole brain connections of drug-naïve patients with early PD. Major changes involved the SMN, DGN, LBN, and VSN, which may be relevant to symptoms of early PD. Additionally, our results support PD as a disconnection syndrome.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, described as the loss of dopaminergic neurons in the substantia nigra pars compacta
Fifty-six individuals with early-stage PD and 54 healthy controls (HCs) were initially enrolled in the study
Scores related to Mini-Mental State Exam (MMSE) (24.41 ± 3.75 vs. 25.58 ± 2.51, p = 0.04), Montreal Cognitive Assessment (MoCA) (18.36 ± 6.21 vs. 23.56 ± 3.37, p < 0.001), Hamilton Anxiety Scale (HAMA) (11.70 ± 7.48 vs. 4.68 ± 3.96, p < 0.001), and Hamilton Depression Scale 24 (HAMD) (11.40 ± 7.92 vs. 4.84 ± 3.25, p < 0.001) were significantly different between the PD and HC groups

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, described as the loss of dopaminergic neurons in the substantia nigra pars compacta. Previous studies on resting state functional magnetic resonance imaging (rs-fMRI) reported that functional connectivity in the frontoparietal regions (de Schipper et al, 2018), occipital cortex (Canu et al, 2015), temporal gyrus (Chen et al, 2015), striatum (Hacker et al, 2012; Agosta et al, 2014), thalamus (Mueller et al, 2019), and basal ganglia (Ma et al, 2017) are affected in PD; PD has been proposed to be a disconnection syndrome owing to its widely affected brain regions and complicated clinical symptoms (CroninGolomb, 2010). A previous study showed changes in whole-brain connectivity among drug-naïve patients using a topological analysis (De Micco et al, 2021a). Another study revealed dynamic changes in the sensorimotor and top-down control networks in patients with PD before and after medication (Chen et al, 2021)

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