Effects of levodopa infusion on motor activation responses in Parkinson's disease.
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 H(2)15O/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).


CONCLUSIONS
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.
Feigin
A
A
Center for Neurosciences, North Shore-LIJ Research Institute, Manhasset, NY 11030, USA. asfeigin@aol.com
Ghilardi
M F
MF
Fukuda
M
M
Mentis
M J
MJ
Dhawan
V
V
Barnes
A
A
Ghez
C P
CP
Eidelberg
D
D
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010104:Oxygen Radioisotopes; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects*; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed / Q000379:methods
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals; D007980:Levodopa