Deep Brain Stimulation Modulates Multiple Abnormal Resting-State Network Connectivity in Patients With Parkinson's Disease

Abstract

Background: Deep brain stimulation (DBS) improves motor and non-motor symptoms in patients with Parkinson's disease (PD). Researchers mainly investigated the motor networks to reveal DBS mechanisms, with few studies extending to other networks. This study aimed to investigate multi-network modulation patterns using DBS in patients with PD.

Methods: Twenty-four patients with PD underwent 1.5 T functional MRI (fMRI) scans in both DBS-on and DBS-off states, with twenty-seven age-matched healthy controls (HCs). Default mode, sensorimotor, salience, and left and right frontoparietal networks were identified by using the independent component analysis. Power spectra and functional connectivity of these networks were calculated. In addition, multiregional connectivity was established from 15 selected regions extracted from the abovementioned networks. Comparisons were made among groups. Finally, correlation analyses were performed between the connectivity changes and symptom improvements.

Results: Compared with HCs, PD-off showed abnormal power spectra and functional connectivity both within and among these networks. Some of the abovementioned abnormalities could be corrected by DBS, including increasing the power spectra in the sensorimotor network and modulating the parts of the ipsilateral functional connectivity in different regions centered in the frontoparietal network. Moreover, the DBS-induced functional connectivity changes were correlated with motor and depression improvements in patients with PD.

Conclusion: DBS modulated the abnormalities in multi-networks. The functional connectivity alterations were associated with motor and psychiatric improvements in PD. This study lays the foundation for large-scale brain network research on multi-network DBS modulation.

Keywords: Parkinson’s disease; deep brain stimulation; frontoparietal network; functional connectivity; power spectra; resting-state network.

FIGURE 1

Resting-state fMRI data preprocessed after the deep brain stimulation (DBS) artifact was filled. An enantiomorphic normalization method was used to fill the artifacts of the raw blood-oxygen-level-dependent (BOLD) data, to improve the accuracy of normalization to the Montreal Neurological Institute (MNI) space. The white arrow shows the artifact lesion. The red arrow shows the filled lesion. The results are displayed from coronal, sagittal, and axial views in three rows. The columns show the raw T1 image, raw BOLD image, and BOLD image after the artifacts were filled; the BOLD image after normalization; and the MNI template from left to right.

FIGURE 2

Selected resting-state networks (RSNs) and comparisons between groups in network level. (A) Selected RSNs (e.g., HC group): DMN, l-FPN, r-FPN, SMN, and SN (distinguished by colors, a one-sample t-test was used, and the threshold of the display was set to the cluster-level false discovery rate (FDR)-corrected P < 0.05). Different functional connectivities of selected networks were compared between (B) HC and PD-off and (C) HC and PD-on (significant differences were shown in gray line); no significant differences were seen between PD-off and PD-on. (D) Power spectra (0.01–0.08 Hz) differences between HC, PD-off, and PD-on within each network. Data are represented as the median (Q1, Q3). ^*,#P < 0.05; ^**P < 0.01; ^***P < 0.001 (*compared with controls, ^#compared with PD-off). HC, healthy control; PD, Parkinson’s disease; SMN, sensorimotor networks; DMN, default mode network; FPN, frontoparietal network; SN, salience network.

FIGURE 3

Different functional connectivities of selected regions of interest (ROIs) among HC, PD-off, and PD-on. (A) Functional connectivity matrix from selected ROIs for HC, PD-off, and PD-on. The color bar indicates the correlation coefficients between ROIs on the right. (B) Different functional connectivities of contralateral (left) and ipsilateral (right) among the three groups are shown separately in the three-dimensional view from the superior perspective. Spheres are shown as ROIs from networks with legends in the right. Lines denote significant differences (P < 0.05, FDR-corrected).

FIGURE 4

DBS reversed the abnormal functional connectivity in patients with PD. (A) Interstate analyses of abnormal functional connectivities. The connections shown in light red represent PD-on > PD-off; dark blue connections refer to PD-off > PD-on. (B) Additionally, these results were presented in the violin graph among the networks. The bars represent the median (Q1, Q3). ^*,#P < 0.05; *^*,##P < 0.01; ^***P < 0.001 (*compared with controls, ^#compared with PD-off).

FIGURE 5

Correlation analysis between functional connectivity changes and DBS improvements for (A) Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III), (B) tremor, (C) rigidity, (D) axial, and (E) the Hamilton Depression scale (HAM-D). The threshold was set to uncorrected P < 0.05. Results surviving to FDR correction were shown in red.