Dopaminergic modulation of cognitive interference after pharmacological washout in Parkinson's disease.
The dopaminergic modulation of prefrontal function in Parkinson's disease (PD) has been consistently demonstrated. There is evidence that the effects of pharmacological manipulations on cognitive performances are described by an "Inverted-U" shaped curve. Neuroimaging studies performed before and after an overnight withdrawal from therapy showed significant differences between drug states, but did not control for the relative impact of the long duration response to levodopa. Here we evaluate the brain response after a complete pharmacological washout by correlating dopaminergic-related changes of this response to changes in performance during cognitive interference. Twelve idiopathic PD patients were studied with functional MRI while performing a modified version of the Stroop task. Patients were scanned twice: (1) following a prolonged washout procedure ("OFF" state) and (2) 90-120 min after the administration of levodopa ("ON" state). Task-related changes of PD patients were compared to those of matched healthy controls. Healthy controls displayed prefrontal and parietal responses that were positively correlated with task accuracy. In the "OFF" state, PD patients showed significant responses in anterior cingulate and pre-supplementary motor area, which are hypothesized to operate at a higher level of basal dopaminergic modulation. Levodopa administration attenuated such responses and enhanced the response of prefrontal cortex (PFC), which was correlated with improved accuracy. Results demonstrate that the behavioral effects of pharmacological manipulations of the dopamine system are highly dependent on the baseline status of PFC. When a true hypodopaminergic state is induced in PD patients, cognitive interference might significantly benefit from the administration of levodopa via an enhanced PFC response.
Neuroradiology Unit, University Magna Graecia, Catanzaro, Italy. f.fera@isn.cnr.it
Francesco
F
Fera
Giuseppe
G
Nicoletti
Antonio
A
Cerasa
Nelide
N
Romeo
Olivier
O
Gallo
Maria C
MC
Gioia
Gennarina
G
Arabia
Pierfrancesco
P
Pugliese
Mario
M
Zappia
Aldo
A
Quattrone
D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D001931:Brain Mapping; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D011897:Random Allocation; D011930:Reaction Time / Q000502:physiology
D000978:Antiparkinson Agents; D007980:Levodopa; D010100:Oxygen; D004298:Dopamine