Objective: To assess influences of dopamine deficiency on the causal interplay within the motor network during bimanual finger tapping in Parkinson’s disease (PD) patients.

Background: Bimanual coordination relies on a complex orchestration of neuronal information within distinct brain areas, including supplementary motor area (SMA), lateral premotor cortex (lPM), primary motor area (M1) and prefrontal cortex (PFC) [1]. Disruption of functional integration of these areas due to dopamine deficiency is thought to underlie impaired motor control in PD [2]. Alterations of causal interplay within this network, however, remain to be elucidated.

Methods: 33 patients diagnosed with idiopathic PD and 32 age-matched controls performed complex bimanual tappings while a 128-channel EEG was recorded. PD patients completed variations of the task 12 hours post withdrawal of their regular dopaminergic medication and following the intake of a standardized dose of L-dopa. Behavioral data was analyzed with regard to error rates and performance time. Subsequently, dynamic causal modelling (DCM) for induced responses was employed to characterize changes of oscillatory coupling between predefined regions of interest. Coupling values were extracted and correlation analysis was performed to relate motor function with effective connectivity.

Results: Behavioural analysis revealed that PD patients off medication made more mistakes compared to healthy participants (PD Off: 42.9 % vs. Control: 29.4 %, p = 0.012), whereas no difference in error rates could be detected for patients in the On-state (PD On: 38.0 % vs. Control: 29.4 %, p = 0.098). Bayesian model selection favored a fully connected model in all groups. Second level analysis revealed no significant coupling between left PFC and premotor areas in the Off-state, whereas left PFC to left lPM coupling was present in the control.In the On-state, however, left PFC to left lPM and SMA coupling was present. Additionally, a significant negative correlation between left PFC to left lPM and SMA coupling with performance time was detected for PD On (Rho = – 0.600, p = 0.011).

Conclusions: Our results suggest that bimanual coordination as well as prefrontal to premotor coupling is affected in PD. Levodopa seems to restore effective connectivity between left PFC and premotor areas and the presence of this influence can be associated with better motor performance.

References: [1] P.A. Loehrer, F.S. Nettersheim, F. Jung, I. Weber, C. Huber, T.A. Dembek, E.A. Pelzer, G.R. Fink, M. Tittgemeyer, L. Timmermann, Ageing changes effective connectivity of motor networks during bimanual finger coordination, NeuroImage. 143 (2016) 325–342. doi:10.1016/j.neuroimage.2016.09.014.

[2] D.M. Herz, H.R. Siebner, O.J. Hulme, E. Florin, M.S. Christensen, L. Timmermann, Levodopa reinstates connectivity from prefrontal to premotor cortex during externally paced movement in Parkinson’s disease, NeuroImage. 90 (2014) 15–23. doi:10.1016/j.neuroimage.2013.11.023.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-substitution-restores-effective-connectivity-between-prefrontal-and-premotor-areas-in-parkinsons-disease/