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  Brain connectivity changes when comparing effects of subthalamic deep brain stimulation with levodopa treatment in Parkinson's disease

Mueller, K., Jech, R., Růžička, F., Holiga, Š., Ballarini, T., Bezdicek, O., et al. (2018). Brain connectivity changes when comparing effects of subthalamic deep brain stimulation with levodopa treatment in Parkinson's disease. NeuroImage: Clinical, 19, 1025-1035. doi:10.1016/j.nicl.2018.05.006.

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Mueller, Karsten1, Author           
Jech, Robert2, Author
Růžička, Filip2, Author
Holiga, Štefan1, Author           
Ballarini, Tommaso3, Author           
Bezdicek, Ondrej2, Author
Möller, Harald E.1, Author           
Vymazal, Josef4, Author
Růžička, Evžen2, Author
Schroeter, Matthias L.3, 5, Author           
Urgošík, Dušan4, Author
1Methods and Development Unit Nuclear Magnetic Resonance, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634558              
2Department of Neurology, First Faculty of Medicine, Charles University, Prague, Czech Republic, ou_persistent22              
3Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
4Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic, ou_persistent22              
5Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              


Free keywords: Deep brain stimulation; Levodopa; Parkinson's disease; Resting state magnetic resonance imaging; Eigenvector centrality; Brain connectivity; Functional connectivity; Nexopathy; Subthalamic nucleus; STN
 Abstract: Levodopa and, later, deep brain stimulation (DBS) have become the mainstays of therapy for motor symptoms associated with Parkinson's disease (PD). Although these therapeutic options lead to similar clinical outcomes, the neural mechanisms underlying their efficacy are different. Therefore, investigating the differential effects of DBS and levodopa on functional brain architecture and associated motor improvement is of paramount interest. Namely, we expected changes in functional brain connectivity patterns when comparing levodopa treatment with DBS.

Clinical assessment and functional magnetic resonance imaging (fMRI) was performed before and after implanting electrodes for DBS in the subthalamic nucleus (STN) in 13 PD patients suffering from severe levodopa-induced motor fluctuations and peak-of-dose dyskinesia. All measurements were acquired in a within subject-design with and without levodopa treatment, and with and without DBS. Brain connectivity changes were computed using eigenvector centrality (EC) that offers a data-driven and parameter-free approach—similarly to Google's PageRank algorithm—revealing brain regions that have an increased connectivity to other regions that are highly connected, too. Both levodopa and DBS led to comparable improvement of motor symptoms as measured with the Unified Parkinson's Disease Rating Scale motor score (UPDRS-III). However, this similar therapeutic effect was underpinned by different connectivity modulations within the motor system. In particular, EC revealed a major increase of interconnectedness in the left and right motor cortex when comparing DBS to levodopa. This was accompanied by an increase of connectivity of these motor hubs with the thalamus and cerebellum.

We observed, for the first time, significant functional connectivity changes when comparing the effects of STN DBS and oral levodopa administration, revealing different treatment-specific mechanisms linked to clinical benefit in PD. Specifically, in contrast to levodopa treatment, STN DBS was associated with increased connectivity within the cortico-thalamo-cerebellar network. Moreover, given the favorable effects of STN DBS on motor complications, the changes in the patients' clinical profile might also contribute to connectivity changes associated with STN-DBS. Understanding the observed connectivity changes may be essential for enhancing the effectiveness of DBS treatment, and for better defining the pathophysiology of the disrupted motor network in PD.


Language(s): eng - English
 Dates: 2018-04-272017-11-302018-05-082018-05-09
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.nicl.2018.05.006
PMID: 30035027
PMC: PMC6051673
Other: eCollection 2018
 Degree: -



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Project name : -
Grant ID : 16-13323S
Funding program : -
Funding organization : Czech Science Foundation “Micro and Macro-Connectomics of the STN nucleus”
Project name : Czech Republic Progres Q27/LF1
Grant ID : -
Funding program : -
Funding organization : Charles University
Project name : -
Grant ID : -
Funding program : (PDF-IRG-1307)
Funding organization : Parkinson's Disease Foundation
Project name : -
Grant ID : MJFF-11362
Funding program : -
Funding organization : Michael J. Fox Foundation

Source 1

Title: NeuroImage: Clinical
Source Genre: Journal
Publ. Info: Elsevier
Pages: - Volume / Issue: 19 Sequence Number: - Start / End Page: 1025 - 1035 Identifier: ISSN: 2213-1582
CoNE: https://pure.mpg.de/cone/journals/resource/2213-1582