Temporal dynamics of cortical and subcortical responses to apomorphine in Parkinson disease: an H2(15)O PET study.
H2(15)O positron emission tomography (PET) was used to study the temporal course of central nervous system (CNS) responses to apomorphine in patients with idiopathic Parkinson disease (PD). Agonist-induced changes in regional cerebral blood flow (rCBF) were evaluated within corticostriatal-thalamocortical circuits as well as in regions that extend beyond the standard pathophysiological model for PD. Compared with controls, rCBF was increased in PD patients in subcortical regions including the basal ganglia and cerebellum and both increased and decreased in prefrontal, parietal, sensorimotor, and paralimbic cortical areas. Apomorphine reversed many of these effects and had widespread effects throughout the brain. We evaluated the effects of apomorphine as they changed over time, comparing rCBF before the motor response and at later times when the motor response was maximal. Apomorphine's effects on functional connectivity also changed over time; activity in the ventrolateral thalamus was coupled with that in the SMA and cerebellum at the time of maximum motor response, but not at 45 seconds. Apomorphine affected rCBF in regions commonly considered part of the pathophysiological model of PD (eg, basal ganglia, thalamus, SMA), and other effects were seen in regions outside of the model (eg, cerebellum and superior parietal lobule). Results are discussed in light of this model.
Hosey
Lara A
LA
Language Section, Voice, Speech, and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
Thompson
Jennifer L W
JL
Metman
Leonard Verhagen
LV
van den Munckhof
Pepyn
P
Braun
Allen R
AR
D000328:Adult; D000368:Aged; D001058:Apomorphine / Q000008:administration & dosage*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010104:Oxygen Radioisotopes; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D013997:Time Factors
D010104:Oxygen Radioisotopes; D001058:Apomorphine