Objective: To assess the influence of dopaminergic depletion in Parkinson’s disease (PD) on connectivity parameters within the cortical motor network.

Background: Integration of neuronal information between the basal ganglia and the cortical motor network is impaired in PD [3]. As a consequence thereof, it has been shown that connectivity between lateral premotor cortex (lPM) and supplementary motor area (SMA) is reduced in PD during a simple tapping task, leading to poor motor output [2]. Changes in coupling within the cortical motor network comprising lPM, SMA, and primary motor cortex (M1), however, are not fully understood and could be used as a surrogate parameter in Parkinson’s disease [1, 3].

Method: 12 patients with idiopathic Parkinson’s disease in their OFF and clinical ON and 12 age-matched controls performed internally and externally paced finger movements while a high-density electroencephalogramm (EEG) was recorded. Behavioral performance was analyzed with respect to deviation of tapping frequency from the given pace. We performed an individual source reconstruction to assure that distinct sources were active. Subsequently, dynamic causal modelling (DCM) for steady states was employed to characterize changes in oscillatory coupling. Bayesian model selection on the family level was performed to analyze overall model structure. In a second step, connectivity parameters were extracted.

Results: PD patients in their OFF had a significantly higher deviation from given pace compared to healthy participants (PD OFF: 61.55 ms ± 10.48 (SEM) vs. Controls: 26.21 ± 1.87 ms, p = .045). In medicated PD patients no significant difference in comparison to controls could be observed (PD OFF: 57.25 ± 9.02 ms vs. Controls: 26.21 ± 1.87 ms, p = .077). Bayesian model selection on the family level favored models comprising reciprocal connections over models with unidirectional connections. Second level analysis revealed a reduction in connectivity between premotor areas (lPM and SMA) and M1 in PD patients OFF medication compared to healthy controls, whereby dopaminergic medication reestablished connectivity.

Conclusion: Our preliminary results suggest that PD patients OFF medication have difficulties maintaining a given tapping pace and coupling between premotor areas and M1 is reduced. Dopaminergic replacement therapy partially improves behavioral performance and premotor to M1 connectivity.

References: 1. de Hemptinne C, Ryapolova-Webb ES, Air EL, Garcia PA, Miller KJ, Ojemann JG, Ostrem JL, Galifianakis NB, Starr PA (2013). Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci U S A. 110(12): 4780-5 2. Herz DM, Florin E, Christensen MS, Reck C, Barbe MT, Tscheuschler MK, Tittgemeyer M, Siebner HR, Timmermann L (2014). Dopamine Replacement Modulates Oscillatory Coupling Between Premotor and Motor Cortical Areas in Parkinson’s Disease. Cerebral Cortex. 24(11): 2873-83 3. Nettersheim FS, Loehrer PA, Weber I, Jung F, Dembek TA, Pelzer EA, Dafsari HS, Huber CA, Tittgemeyer M, Timmermann L (2018). Dopamine substitution alters effective connectivity of cortical prefrontal, premotor, and motor regions during complex bimanual finger movements in Parkinson’s disease. Neuroimage:

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-substitution-increases-connectivity-between-premotor-and-motor-areas-in-parkinsons-disease-a-dcm-study/