title: Flow-metabolism dissociation in the pathogenesis of levodopa-induced dyskinesia.
abstract: Levodopa-induced dyskinesia (LID) is the most common, disruptive complication of Parkinson's disease (PD) pharmacotherapy, yet despite decades of research, the changes in regional brain function underlying LID remain largely unknown. We previously found that the cerebral vasomotor and metabolic responses to levodopa are dissociated in PD subjects. Nonetheless, it is unclear whether levodopa-mediated dissociation is exaggerated in LID or distinguishes LID from non-LID subjects. To explore this possibility, we used dual-tracer positron emission tomography to quantify regional cerebral blood flow and metabolic activity in 28 PD subjects (14 LID, 14 non-LID), scanned before and during intravenous levodopa infusion. Levodopa-mediated dissociation was most prominent in the posterior putamen (P< 0.0001) and greater in LID than in non-LID and test-retest subjects. Strikingly, LID subjects also showed increased sensorimotor cortex (SMC) activity in the baseline, unmedicated state. Imaging data from an independent PD sample (106 subjects) linked these differences to loss of mesocortical dopamine terminals in advanced patients. In aggregate, the data suggest that LID results from an overactive vasomotor response to levodopa in the putamen on a background of disease-related increases in SMC activity. LID may thus be amenable to treatment that modulates the function of these 2 regions.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Jourdain
authors.forename: Chris C
authors.initials: CC
authors.lastname: Tang
authors.forename: Florian
authors.initials: F
authors.lastname: Holtbernd
authors.forename: Christian
authors.initials: C
authors.lastname: Dresel
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Yilong
authors.initials: Y
authors.lastname: Ma
authors.forename: Vijay
authors.initials: V
authors.lastname: Dhawan
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004298:Dopamine; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D014666:Vasomotor System
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D004298:Dopamine