Nature Medicine
3, 671 - 674 (1997)
doi:10.1038/nm0697-671
Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptomsKaren D. Davis1, Ethan Taub1, Sylvain Houle2, Anthony E. Lang3, Jonathan O. Dostrovsky4, Ronald R. Tasker1
& Anders M. Lozano1, 5
1Division of Neurosurgery, Department of Surgery, University of Toronto/The Toronto Hospital (Western Division),399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8
2The PET Centre, Clarke Institute of Psychiatry, 250 College Street, University of Toronto,Toronto, Ontario, Canada M5T 1R8
3Division of Neurology, Department of Medicine, University of Toronto/The Toronto Hospital (Western Division),399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8
4Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
5Correspondence should be addressed to A.M.L. Studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in monkeys1,2 suggest that excessive inhibitory outflow from the internal segment of the globus pallidus (GPi) suppresses the motor thalamus, which reduces activation of the cerebral cortex motor system, resulting in the slowness and poverty of movement of Parkinson's disease (PD)3. This hypothesis is supported by reports of high rates of spontaneous neuronal discharges and hypermetabolism in GPi (ref. 4−7) and impaired activation of the supplementary motor area (SMA) and dorsolateral prefrontal regions8,9 in PD patients. Furthermore, lesion or chronic high-frequency electrical (likely inactivating) stimulation of GPi (ref. 10−14) is associated with marked improvements in akinesia and rigidity, and the impaired activation of SMA is reversed when the akinesia is treated with dopamine agonists15. To test whether improvement in motor function with pallidal surgery can be attributed to increased activity in premotor cortical regions, we assessed the changes in regional cerebral blood flow (rCBF) and parkinsonian symptoms during disruption of GPi activity with high-frequency stimulation delivered through implanted brain electrodes. Positron emission tomography (PET) revealed an increase in rCBF in ipsi-lateral premotor cortical areas during GPi stimulation, which improved rigidity and bradykinesia. These results suggest that disrupting the excessive inhibitory output of the basal ganglia reverses parkinsonism, via a thalamic relay, by activation of brain areas involved in the initiation of movement.
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