Objective: To determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN-DBS.

Background: In Parkinson’s disease (PD), dopamine replacement therapy (DRT) modulates a cortico-striatal network and improves bradykinesia by enhancing the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on Parkinsonian signs appear to go beyond the effects of DRT including highly beneficial tremor suppression.

Methods: Twenty-six medicated PD patients (mean age 61.5 years (SD 8.67), mean disease duration 11 years (SD 3.60)) were investigated in a 1.5 T MRI scanner (i) during bipolar stimulation and (ii) while the stimulator was switched off, and resting state fMRI sequences were acquired. Dynamic causal modelling was performed using ROIs from a motor network including PFC, premotor cortex (PMC), SMA, M1, putamen, thalamus and contralateral cerebellum. Due to hardware-related artifacts, the right hemisphere could be analyzed in 25 patients and the left hemisphere in ten.

Results: DBS improved the UPDRSIII by 28.6% (SD 0.15) (DBS on/Med on vs. DBS off/Med on). Active stimulation resulted in an increased effective connectivity of the PFC to the cerebellum and a decreased effective connectivity of the thalamus to the cerebellum. Further, the cerebellar outflow to the putamen and the SMA was strengthened, and effective connectivity of putamen to M1 was decreased. In addition, the intrinsic connectivity of the PFC, PMC, SMA, thalamus and cerebellum was increased following DBS.

Conclusions: DBS-related improvement of Parkinsonian signs is driven by a prefronto-cerebellar network bypassing the striatum. DBS-related modulation of cerebellar activity resulted in an implementation of DBS effects via a cerebello-striatal loop. Activation of the mesial premotor loop (PFC-SMA) may thus be secondary due to the primary modulation of cerebellar networks. Reduced putamen-M1 connectivity may reflect a normalization of an otherwise hyper-connected state in PD which has been associated with poorer motor performance. Further, our results strengthen the notion that the striato-pallido-thalamic and the cerebello-thalamic loop are strongly interconnected which is corroborated by animal studies that show direct disynaptic connection between both, STN and putamen and cerebellum.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-subthalamic-nucleus-deep-brain-stimulation-in-parkinsons-disease-are-mediated-by-a-prefronto-cerebellar-striatal-loop/