title: Effects of dopaminergic treatment on functional cortico-cortical connectivity in Parkinson's disease.
abstract: Interactions between dorsal premotor cortex (PMd) and primary motor cortex (M1) and interhemispheric inhibition (IHI) between M1 are impaired in Parkinson's disease (PD). We used dual-site transcranial magnetic stimulation to compare effects of first-time levodopa application with chronic dopaminergic therapy on these interactions in PD. Twelve untreated PD patients were studied before and after their first-ever intake of levodopa. The effects of chronic dopaminergic medication were evaluated in 11 patients who had received regular dopaminergic medication for approximately 3 years. Nine of these patients were also measured after overnight withdrawal of medication. For IHI, conditioning stimuli (CS) were applied to left M1 followed by test stimuli (TS) over right M1 and vice versa in separate blocks at interstimulus intervals (ISI) of 6-10 ms. Next, CS were applied to left PMd at subthreshold intensity followed by TS over left M1 at ISIs of 4 and 6 ms. Results were compared to 17 age- and gender-matched controls. In de novo PD patients, levodopa reduced left-to-right IHI, but did not alter PMd-M1 connectivity. In contrast, inhibitory PMd-M1 connectivity was present in early disease patients under chronic dopaminergic stimulation, but not in de novo PD patients at low stimulus intensities at an ISI of 4 ms. First-time exposure to levodopa exerts different effects on cortico-cortical pathways than chronic dopaminergic stimulation in PD, suggesting a change in the responsiveness of cortico-cortical circuits during the course of PD.
authors.affiliation: Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Str. 1, 23562, Lübeck, Germany, simone.zittel@neuro.uni-luebeck.de.
authors.forename: S
authors.initials: S
authors.lastname: Zittel
authors.forename: C
authors.initials: C
authors.lastname: Heinbokel
authors.forename: J P M
authors.initials: JP
authors.lastname: van der Vegt
authors.forename: E
authors.initials: E
authors.lastname: Niessen
authors.forename: C
authors.initials: C
authors.lastname: Buhmann
authors.forename: C
authors.initials: C
authors.lastname: Gerloff
authors.forename: H R
authors.initials: HR
authors.lastname: Siebner
authors.forename: A
authors.initials: A
authors.lastname: Münchau
authors.forename: T
authors.initials: T
authors.lastname: Bäumer
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa