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NEUROLOGY 2005;64:1906-1912
© 2005 American Academy of Neurology

Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease

P. Mir, MD*, K. Matsunaga, MD*, F. Gilio, MD, N. P. Quinn, MD, H. R. Siebner, MD and J. C. Rothwell, PhD

From the Sobell Department of Motor Neuroscience and Movement Disorders (Drs. Mir, Matsunaga, Quinn, and Rothwell), Institute of Neurology, London, UK; Servicio de Neurología (Dr. Mir), Hospital Universitario Virgen del Rocío, Seville, Spain; Department of Neurological Sciences (Dr. Gilio), University of Rome La Sapienza, INM Neuromed IRCCS, Pozzilli, Italy; Department of Neurology (Dr. Siebner), Christian Albrechts University, Kiel, Germany; and NeuroImageNord Hamburg-Kiel-Luebeck (Dr. Siebner), Germany.

Address correspondence and reprint requests to Dr Rothwell, Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology (Box 146), Queen Square, London WC1N 3BG, UK; e-mail: j.rothwell{at}ion.ucl.ac.uk

Objective: To explore the impact of dopaminergic therapy on facilitatory premotor-motor interactions in patients with Parkinson disease (PD).

Methods: Ten patients with PD and 10 age-matched healthy volunteers received repetitive transcranial magnetic stimulation (rTMS) over the left dorsal premotor cortex (5 Hz, 1,500 stimuli, 90% of active motor threshold). Patients were studied while "on" and "off" medication. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseus muscle before and after rTMS to quantify changes in motor cortical excitability. The after-effects of rTMS on motor function were assessed using the Unified Parkinson's Disease Rating Scale and the kinematics of ballistic wrist flexions.

Results: MEPs evoked from the ipsilateral motor cortex were increased after premotor rTMS in relaxed normal subjects, consistent with an increase in motor cortex excitability. In patients with PD, the effect of premotor rTMS was modified by medication. When patients were in a practically defined "off" state, premotor rTMS had no effect on MEPs, whereas when they were in the "on" state, premotor rTMS facilitated MEPs. Premotor rTMS had no effect on clinical parkinsonian symptoms or motor performance of ballistic wrist movements, regardless of whether patients were in the "on" or "off" state.

Conclusions: In Parkinson disease, the ability of premotor-motor connections to increase motor cortical excitability is defective but restored to normal by dopaminergic medication. Dopamine deficiency in the basal ganglia may affect the way that frontal motor areas interact with each other.

*Drs. Mir and Matsunaga contributed equally to this work.

Funded by the Medical Research Council (UK).

Received September 15, 2004. Accepted in final form March 1, 2005.






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