Brain Advance Access published online on November 26, 2008
Brain, doi:10.1093/brain/awn309
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Temporal dynamics of basal ganglia under-recruitment in Parkinson's disease: transient caudate abnormalities during updating of working memory
1Department of Psychology, Stockholm University and Stockholm Brain Institute, 2Department of Radiation Sciences, Radiation Physics, 3Department of Community Medicine and Rehabilitation, Geriatric Medicine, 4Department of Pharmacology and Clinical Neuroscience, Neurology, 5Department of Radiation Sciences, Diagnostic Radiology and 6Department of Integrative Medical Biology, Umeå University, Sweden
Correspondence to:
Dr Petter Marklund, Department of Psychology, Stockholm University, Stockholm, 10691, Sweden E-mail: Petter.Marklund{at}psychology.su.se
Using hybrid-blocked/event-related fMRI and the 2-back task we aimed to decompose tonic and phasic temporal dynamics of basal ganglia response abnormalities in working memory associated with early untreated Parkinson's disease. In view of the tonic/phasic dopamine hypothesis, which posits a functional division between phasic D2-dependent striatal updating processes and tonic D1-dependent prefrontal context-maintenance processes, we predicted that newly diagnosed, drug-naïve Parkinson's disease patients, with selective striatal dopamine deprivation, would demonstrate transient rather than sustained activation changes in the basal ganglia during 2-back performance. Task-related activation patterns within discrete basal ganglia structures were directly compared between patients and healthy elderly controls. The obtained results yielded uniquely transient underactivation foci in caudate nuclei, putamen and globus pallidus in Parkinson's disease patients, which indicates suboptimal phasic implementation of striatal D2-dependent gating mechanisms during updating. Sustained underactivation was only seen in the anterior putamen, which may reflect initial signs of tonic control impairment. No significant changes were exhibited in prefrontal cortex. The present findings resonate well with the tonic/phasic dopamine account and suggest that basal ganglia under-recruitment associated with executive dysfunction in early Parkinson's disease might predominantly stem from deficiencies in phasic executive components subserved by striatum.
Key Words: Parkinson's disease; hybrid fMRI; cognitive control dynamics; verbal working memory; Striatum
Abbreviations: BG, basal ganglia; DA, dopamine; fMRI, functional magnetic resonance imaging; PET, positron emission tomography; WM, working memory
Received April 7, 2008. Revised September 3, 2008. Accepted October 30, 2008.