title: Degradation of stored movement representations in the Parkinsonian brain and the impact of levodopa.
abstract: Parkinson's disease (PD) results from the depletion of dopamine and other neurotransmitters within the basal ganglia, and is typically characterized by motor impairment (e.g., bradykinesia) and difficulty initiating voluntary movements. Difficulty initiating a movement may result from a deficit in accessing or executing a stored representation of the movement, or having to create a new representation each time a movement is required. To date, it is unclear which may be responsible for movement initiation impairments observed in PD. In this study, we used functional magnetic resonance imaging and a task in which participants passively viewed familiar and unfamiliar graspable objects, with no confounding motor task component. Our results show that the brains of PD patients implicitly analyze familiar graspable objects as if the brain has little or no motor experience with the objects. This was observed as a lack of differential activity within brain regions associated with stored movement representations for familiar objects relative to unfamiliar objects, as well as significantly greater activity for familiar objects when off levodopa relative to on medication. Symptom severity modulated this activity difference within the basal ganglia. Levodopa appears to normalize brain activity, but its effect may be one of attenuation of brain hyperactivity within the basal ganglia network, which is responsible for controlling motor behavior and the integration of visuomotor information. Overall, this study demonstrates that difficulty initiating voluntary movements experienced by PD patients may be the result of degradation in stored representations responsible for the movement.
authors.affiliation: Department of Medical Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Jolyn N A
authors.initials: JN
authors.lastname: D'Andrea
authors.forename: Angela M
authors.initials: AM
authors.lastname: Haffenden
authors.forename: Sarah
authors.initials: S
authors.lastname: Furtado
authors.forename: Oksana
authors.initials: O
authors.lastname: Suchowersky
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Goodyear
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000473:pathology*; D010775:Photic Stimulation; D011930:Reaction Time / Q000187:drug effects; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D010100:Oxygen