Executive dysfunction in Parkinson's disease is associated with altered pallidal-frontal processing.
Executive dysfunction in Parkinson's disease is well documented, but it is still unclear whether this results from (i) prefrontal dysfunction, (ii) striatal dysfunction, or (iii) altered striatal outflow to the prefrontal cortex. To clarify this issue, we used H(2)(15)O PET to asses six nondemented and nondepressed patients with Parkinson's disease and six matched controls while they performed a task involving executive function, random number generation (RNG), and a control counting task. To assess the effect of increasing task demands, each task was performed at three rates. Both groups showed significant increase in nonrandomness of responses during RNG at faster rates, which was differentially greater for the patients at the faster rate. The controls showed significant activation of the lateral and medial prefrontal cortex and superior and medial parietal cortex during RNG relative to counting. For the same comparison, the patients did not show any activity in medial frontal structures. The controls showed significantly greater mesial frontotemporal activation during counting than RNG, whereas the patients did not show any modulation of regional cerebral blood flow (rCBF) in these areas with task. With faster rates of RNG, the controls showed rCBF increase in the right internal segment of globus pallidus (GPi) and a decrease in frontal cortex. The patients showed the opposite pattern of subcortical and frontal rCBF change with faster rates. The results suggest that executive dysfunction in Parkinson's disease is associated with a failure to modulate frontal activation with increased task demands (nature of task or rate), a deficit associated with altered rCBF in the GPi, the final basal ganglia output pathway to frontal cortex rather than any intrinsic prefrontal dysfunction.
Dirnberger
Georg
G
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
Frith
Chris D
CD
Jahanshahi
Marjan
M
D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D005917:Globus Pallidus / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000503:physiopathology*