Dynamics of Top-Down Control and Motor Networks in Parkinson's Disease

Abstract

Background: Motor symptoms in Parkinson's disease (PD) patients might be related to high-level task-control deficits. We aimed at investigating the dynamics between sensorimotor network and top-down control networks (frontal-parietal, cingulo-opercular, and cerebellar) in PD and at determining the effects of levodopa on the dynamics of these networks.

Methods: We investigated dynamic functional connectivity (dFC), during resting state functional magnetic resonance imaging, between sensorimotor network and top-down control networks in 36 PD patients (OFF medication, PD-OFF) and 36 healthy volunteers. We further assessed the effect of medication on dFC in18 PD patients who were also scanned ON medication.

Results: The dFC analyses identified three discrete states: State I (35.68%) characterized by connections between the cerebellum and sensorimotor network, State II (34.17%) with connections between the sensorimotor and frontal-parietal network, and State III (30.15%) with connection between the sensorimotor and cingulo-opercular network. PD patients have significantly fewer occurrences and overall spent less time (shorter dwell time) in State II compared to healthy controls. After levodopa intake, dwell time improved toward normal. The change in dwell time before and after taking levodopa was negatively related to the respective changes in Unified Parkinson's Disease Rating Scale, Part III. PD-OFF showed significantly decreased connectivity between sensorimotor and control networks and increased connectivity within control networks. These changes were partially improved after levodopa intake.

Conclusions: Dopamine depletion in PD is associated with abnormalities in temporal and spatial properties between cognitive control and sensorimotor network, possibly contributing to clinical deficits. Levodopa partially restores the network function toward the values observed in healthy volunteers. © 2021 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; dopamine; dynamic functional connectivity; motor network; top-down control networks.

FIG. 1.

Overview of the dynamic FC analysis steps and results of the clustering analysis per state. (A) Schematic diagram of the relationship between control network and SMN, and CB (n = 13), CON (n = 31), FPN (n = 21), and SMN (n = 33) network nodes were derived from Dosenbach et al. (B) Dynamic FC computed using a sliding window approach. (C) Resulting cluster centroids for each state. The total number of occurrences and percentage of total occurrences are listed above each cluster median. (D) Graphical representation of the top 5% functional coupling in each state. CB, cerebellum; CON, cingulo-opercular network; FC, functional connectivity; FPN, frontoparietal network; SMN, sensorimotor network.

FIG. 2.

Functional connectivity state results. (A) HV and PD-specific cluster centroids for each state: the number of occurrences for PDs and HVs and the percentage of occurrences for HVs and PDs are listed above each cluster median. (B) Graphical representation of the top 5% functional coupling in each state for HVs and PDs. CB, cerebellum; CON, cingulo-opercular network; FPN, frontoparietal network; HV, healthy volunteers; PD, Parkinson’s disease; SMN, sensorimotor network.

FIG. 3.

Between-group comparison in temporal properties of functional connectivity state results. (A) Comparison of fractional window between HV and PD and between (B) OFF and ON medication. (C) Comparison of mean dwell time between HV and PD and between (D) OFF and ON medication. (E) Correlation between change in UPDRS III score and change in MDT of State II. (F) Comparison of number of transitions between HV and PD and between (G) OFF and ON medication. HV, healthy volunteers; MDT, mean dwell time; PD, Parkinson’s disease; UPDRS, Unified Parkinson’s Disease Rating Scale.

FIG. 4.

Alteration of functional connectivity for each state between HV and PD groups and between OFF and ON medication. (A) Functional connectivity differences between HV and PD in each state. Red lines represent reduced connection, whereas blue line are increased connections in PD compared with HV for each state. (B) Functional connectivity differences between OFF and ON medication in each state. Blue lines represent reduced connection, whereas red lines are increased connections in ON medication compared with OFF medication for each state. HV, healthy volunteers; Inf, inferior; IPL, inferior partial lobule; L, left; Lat, lateral; Med, medial; Mid, middle; PD, Parkinson’s disease; PFC, prefrontal cortex; pre-CG, precentral gyrus; R, right; SMA, supplementary motor area; TPJ, temporoparietal junction.