Dopamine Replacement Modulates Oscillatory Coupling Between Premotor and Motor Cortical Areas in Parkinson's Disease

1. Damian Marc Herz1,2, 
2. Esther Florin1,3,4, 
3. Mark Schram Christensen2,5,6, 
4. Christiane Reck1, 
5. Michael Thomas Barbe1,3, 
6. Maike Karoline Tscheuschler1, 
7. Marc Tittgemeyer7, 
8. Hartwig Roman Siebner2 and 
9. Lars Timmermann1

+Author Affiliations

1. ¹Department of Neurology, University Hospital Cologne, Cologne, Germany,
2. ²Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark,
3. ³Cognitive Neurology Section, Institute of Neurosciences and Medicine (INM-3), Research Centre Juelich, Juelich, Germany,
4. ⁴McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada,
5. ⁵Department of Nutrition, Exercise and Sports,
6. ⁶Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark and
7. ⁷Max Planck Institute for Neurological Research, Cologne, Germany

1. Address correspondence to Damian Marc Herz, Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark. Email: damianh@drcmr.dk

Abstract

Efficient neural communication between premotor and motor cortical areas is critical for manual motor control. Here, we used high-density electroencephalography to study cortical connectivity in patients with Parkinson's disease (PD) and age-matched healthy controls while they performed repetitive movements of the right index finger at maximal repetition rate. Multiple source beamformer analysis and dynamic causal modeling were used to assess oscillatory coupling between the lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1) in the contralateral hemisphere. Elderly healthy controls showed task-related modulation in connections from lPM to SMA and M1, mainly within the γ-band (>30 Hz). Nonmedicated PD patients also showed task-related γ-γ coupling from lPM to M1, but γ coupling from lPM to SMA was absent. Levodopa reinstated physiological γ-γ coupling from lPM to SMA and significantly strengthened coupling in the feedback connection from M1 to lPM expressed as β-β as well as θ-β coupling. Enhancement in cross-frequency θ-β coupling from M1 to lPM was correlated with levodopa-induced improvement in motor function. The results show that PD is associated with an altered neural communication between premotor and motor cortical areas, which can be modulated by dopamine replacement.