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Functional Connectivity Changes of Key Regions for Motor Initiation in Parkinson's Disease.

ABSTRACT: Akinesia, a cardinal symptom of Parkinson's disease, has been linked to abnormal activation in putamen and posterior medial frontal cortex (pMFC). However, little is known whether clinical severity of akinesia is linked to dysfunctional connectivity of these regions. Using a seed-based approach, we here investigated resting-state functional connectivity (RSFC) of putamen, pMFC and primary motor cortex (M1) in 60 patients with Parkinson's disease on regular medication and 72 healthy controls. We found that in patients putamen featured decreases of connectivity for a number of cortical and subcortical areas engaged in sensorimotor and cognitive processing. In contrast, the pMFC showed reduced connectivity with a more focal cortical network involved in higher-level motor-cognition. Finally, M1 featured a selective disruption of connectivity in a network specifically connected with M1. Correlating clinical impairment with connectivity changes revealed a relationship between akinesia and reduced RSFC between pMFC and left intraparietal lobule (IPL). Together, the present study demonstrated RSFC decreases in networks for motor initiation and execution in Parkinson's disease. Moreover, results suggest a relationship between pMFC-IPL decoupling and the manifestation of akinetic symptoms.

SUBMITTER: Hensel L

PROVIDER: S-EPMC6294405 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Functional Connectivity Changes of Key Regions for Motor Initiation in Parkinson's Disease.

Hensel Lukas L Hoffstaedter Felix F Caspers Julian J Michely Jochen J Mathys Christian C Heller Julia J Eickhoff Claudia R CR Reetz Kathrin K Südmeyer Martin M Fink Gereon R GR Schnitzler Alfons A Grefkes Christian C Eickhoff Simon B SB

Cerebral cortex (New York, N.Y. : 1991) 20190101 1

Akinesia, a cardinal symptom of Parkinson's disease, has been linked to abnormal activation in putamen and posterior medial frontal cortex (pMFC). However, little is known whether clinical severity of akinesia is linked to dysfunctional connectivity of these regions. Using a seed-based approach, we here investigated resting-state functional connectivity (RSFC) of putamen, pMFC and primary motor cortex (M1) in 60 patients with Parkinson's disease on regular medication and 72 healthy controls. We ...[more]

PMID: 30418548

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Project description:BackgroundThe primary motor cortex (M1) is a critical node in Parkinson's disease (PD)-related motor circuitry; however, the functional roles of its subregions are poorly understood. In this study, we investigated changes in the functional connectivity patterns of M1 subregions and their relationships to improved clinical symptoms following levodopa administration.MethodsThirty-six PD patients and 37 healthy controls (HCs) were enrolled. A formal levodopa challenge test was conducted in the PD group, and the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III) was assessed before (off state) and 1 h after administration of levodopa (on state). The PD group underwent resting-state functional magnetic resonance imaging in both off and on states, whereas the HC group was scanned once. We used the Human Brainnetome Atlas template to subdivide M1 into twelve regions of interest (ROIs). Functional connectivity (FC) was compared between PD on and off states [paired t-test, voxel-level p < 0.001, cluster-level p < 0.05, Gaussian random field (GRF) correction] and between patients and HC (two-sample t-test voxel-level p < 0.001, cluster-level p < 0.05). Correlations between ΔFC (differences in FC between PD off and on states) and clinical symptom improvements were examined.ResultsThere was decreased FC between the right caudal dorsolateral area 6 and the anterior cingulate gyrus (ACC), the right upper limb region and the left medial dorsal thalamus (mdTHA), as well as increased FC between the left tongue and larynx region and the left medial frontal gyrus. ΔFC between the right caudal dorsolateral area 6 and ACC was positively correlated with improvements in UPDRS-III total scores as well as the rigidity (item 22) and bradykinesia (items 23-26 and 31) subscores. ΔFC between the right upper limb region and left thalamus was positively correlated with improvements in the left upper limb tremor (items 20c and 21b) and postural tremor (item 21b) subscores.ConclusionsOur results reveal novel information regarding the underlying mechanisms in the motor circuits in the M1 and a promising way to explore the internal function of the M1 in PD patients. Notably, M1 is a potential therapeutic target in PD, and the exploration of its subregions provides a basis and a source of new insights for clinical intervention and precise drug treatment.

Project description:Dynamic functional connectivity captures temporal variations of functional connectivity during MRI acquisition and it may be a suitable method to detect cognitive changes in Parkinson's disease. In this study, we evaluated 118 patients with Parkinson's disease matched for age, sex and education with 35 healthy control subjects. Patients with Parkinson's disease were classified with normal cognition (n = 52), mild cognitive impairment (n = 46), and dementia (n = 20) based on an extensive neuropsychological evaluation. Resting state functional MRI and a sliding-window approach were used to study the dynamic functional connectivity. Dynamic analysis suggested two distinct connectivity 'States' across the entire group: a more frequent, segregated brain state characterized by the predominance of within-network connections, State I, and a less frequent, integrated state with strongly connected functional internetwork components, State II. In Parkinson's disease, State I occurred 13.89% more often than in healthy control subjects, paralleled by a proportional reduction of State II. Parkinson's disease subgroups analyses showed the segregated state occurred more frequently in Parkinson's disease dementia than in mild cognitive impairment and normal cognition groups. Further, patients with Parkinson's disease dementia dwelled significantly longer in the segregated State I, and showed a significant lower number of transitions to the strongly interconnected State II compared to the other subgroups. Our study indicates that dementia in Parkinson's disease is characterized by altered temporal properties in dynamic connectivity. In addition, our results show that increased dwell time in the segregated state and reduced number of transitions between states are associated with presence of dementia in Parkinson's disease. Further studies on dynamic functional connectivity changes could help to better understand the progressive dysfunction of networks between Parkinson's disease cognitive states.

Dataset Information

Functional Connectivity Changes of Key Regions for Motor Initiation in Parkinson's Disease.

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Functional Connectivity Changes of Key Regions for Motor Initiation in Parkinson's Disease.

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