Objective: To perform a direct comparison between the effect of levodopa medication and deep brain stimulation of the subthalamic nucleus (STN DBS) on functional brain connectivity in the same group of patients with Parkinson’s disease (PD) examined before and after electrode implantation.

Background: Underlying mechanism of levodopa and STN DBS in PD is different despite their similar clinical effects on motor function.

Methods: The Unified Parkinson’s Disease Rating Scale motor score (UPDRS-III) and functional magnetic resonance imaging (fMRI) were acquired before and after implanting electrodes bilaterally into STN in 13 PD patients (Hoehn-Yahr stages II-III, 11 males, age 52.8±6.9 y, disease duration 12.6±2.7 y). Imaging was performed using a 1.5-T scanner (Siemens, Germany) and T2*-weighted gradient echo echo-planar imaging (EPI) (repetition time, TR=3 s; echo time, TE=51 ms, 200 repetitions). All measurements were acquired in a within-subject design with and without levodopa treatment, and with and without unilateral STN DBS connected to the external stimulator. 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 a high connectivity to other regions that are highly connected.

Results: Both levodopa and STN DBS led to comparable improvement of motor symptoms as measured with the 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 STN DBS to levodopa. This was accompanied by an increase of connectivity of these motor hubs with the thalamus and cerebellum. [figure1]

Conclusions: Conclusions: 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. 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. Supported by GAČR 16-13323S, PDF-IRG-1307, and MJFF-11362.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/higher-motor-cortex-connectivity-with-subthalamic-stimulation-than-with-levodopa-a-resting-state-fmri-study-in-parkinsons-disease/