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Effects of levodopa infusion on motor activation responses in Parkinson’s disease

From the Center for Neurosciences (Drs. Feigin, Fukuda, Mentis, Dhawan, Barnes, and Eidelberg), North Shore–LIJ Research Institute, Manhasset; Department of Neurology (Drs. Feigin, Fukuda, Dhawan, and Eidelberg), North Shore University Hospital, Manhasset; New York University School of Medicine (Drs. Ghilardi and Ghez); and Center of Neurobiology and Behavior (Drs. Ghilardi and Ghez), Columbia University, New York, NY.

Address correspondence and reprint requests to Dr. Feigin, Center for Neurosciences, 350 Community Drive, Manhasset, NY 11030; e-mail: asfeigin{at}aol.com

Background: Clinical improvement with levodopa therapy for PD is associated with specific regional changes in cerebral glucose metabolism. However, it is unknown how these effects of treatment in the resting state relate to alterations in brain function that occur during movement. In this study, the authors used PET to assess the effects of levodopa on motor activation responses and determined how these changes related to on-line recordings of movement speed and accuracy.

Methods: Seven right-handed PD patients were scanned with H₂¹⁵O/PET while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed during "on" and "off" states with an individually titrated constant rate levodopa infusion; movements were kinematically controlled across treatment conditions.

Results: Levodopa improved "off" state UPDRS motor ratings (34%; p < 0.006) and movement time (18%; p = 0.001). Spatial errors worsened during levodopa infusion (24%; p = 0.02). Concurrent regional cerebral blood flow (rCBF) recordings revealed significant enhancement of motor activation responses in the posterior putamen bilaterally (p < 0.001), left ventral thalamus (p < 0.002), and pons (p < 0.005). Movement time improvement with treatment correlated with rCBF increases in the left globus pallidus and left ventral thalamus (p < 0.01). By contrast, the increase in spatial errors correlated with rCBF increases in the cerebellar vermis (p < 0.01).

Conclusion: These results suggest that levodopa infusion may improve aspects of motor performance while worsening others. Different components of the motor cortico-striato-pallido-thalamo-cortical loop and related pathways may underlie motor improvement and adverse motoric effects of levodopa therapy for PD.

This article has been cited by other articles:

				A. Feigin, M. F. Ghilardi, M. Carbon, C. Edwards, M. Fukuda, V. Dhawan, C. Margouleff, C. Ghez, and D. Eidelberg Effects of levodopa on motor sequence learning in Parkinson's disease Neurology, June 10, 2003; 60(11): 1744 - 1749. [Abstract] [Full Text] [PDF]