BACKGROUND AND PURPOSE: Wearing-off is one of the most frequent problems 
encountered by levodopa-treated patients. Entacapone, a peripheral inhibitor of 
catechol-O-methyltransferase (COMT), reduces this motor complication by 
prolonging the effect of levodopa. We sought to understand the impact of 
COMT-inhibition on movement execution in PD patients with wearing-off by 
comparing functional magnetic resonance imaging (f-MRI) activation patterns 
prior to and during entacapone treatment. Our hypothesis was to determine 
whether changes in cortical activation are associated to COMT-inhibitor 
treatment.
METHODS: Nine levodopa-treated non-demented PD patients with wearing-off were 
prospectively studied in two f-MRI session, prior to and during entacapone 
treatment. A group of control subjects were also studied for comparison.
RESULTS: The patients significantly improved under COMT-inhibitor treatment 
based on home diaries. F-MRI results showed that at baseline the patients 
presented a bilateral activation of the primary motor, controlateral premotor 
cortex and supplementary motor area, as well as ipsilateral cerebellum. During 
treatment with entacapone, PD patients showed reductions in the activations of 
these cortical areas and a decreased activation in the ipsilateral cerebellum.
CONCLUSIONS: Our preliminary findings indicate that f-MRI is able to detect 
cortical activation changes during long-term modulation of dopaminergic 
treatment in PD patients with wearing-off, and thus, this technique could be 
further investigated in advanced PD patients.