Brain Advance Access originally published online on March 24, 2008
Brain 2008 131(5):1294-1302; doi:10.1093/brain/awn054
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Cognitive deficits and striato-frontal dopamine release in Parkinson's disease
1Division of Neuroscience and MRC Clinical Sciences Centre, Imperial College School of Medicine and 2Hammersmith Imanet, GE Healthcare, Hammersmith Hospital, London W12 0NN, UK
Correspondence to: Nobukatsu Sawamoto, MD, PhD, Neurology Group, MRC Cyclotron Building, Division of Neuroscience and MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK E-mail: nobukatsu.sawamoto{at}csc.mrc.ac.uk or sawa{at}kuhp.kyoto-u.ac.jp
Idiopathic Parkinson's disease (PD) is often accompanied by a pattern of executive deficits similar to those found in patients with frontal lobe lesions. We investigated whether such cognitive deficits are attributable to frontal lobe dysfunction as a direct consequence of impaired mesocortical dopaminergic transmission or an indirect consequence of impaired nigrostriatal dopaminergic function. For this purpose, changes in synaptic dopamine levels during task performance were monitored using a marker of dopamine D2-receptor availability 11C-raclopride (RAC) PET. During RAC PET, seven patients with early symptomatic PD and seven age-matched healthy controls performed two types of behavioural task, a spatial working memory task (SWT) and a visuomotor control task (VMT). The SWT involves an executive process which is known to be impaired by both frontal lobe lesions and PD while the VMT is a control test for the visuomotor component of the SWT. Parametric images of RAC binding potential during performance of each task were generated, and compared between the tasks using voxel-based statistical parametric mapping as well as region of interest analysis. In controls, RAC binding was reduced in the dorsal caudate during performance of the SWT compared with the VMT, compatible with increased levels of endogenous dopamine release due to the executive process. In PD patients, this RAC binding reduction was not observed. In contrast, RAC binding in the anterior cingulate cortex within the medial prefrontal cortex was reduced by a comparable level during the SWT both in controls and PD patients. Statistical comparisons between controls and PD patients confirmed significantly attenuated dopamine release in the dorsal caudate in PD, but preserved levels of medial prefrontal dopamine release. Our data suggest that executive deficits in early patients with PD are associated with impaired nigrostriatal dopaminergic function resulting in abnormal processing in the cortico-basal ganglia circuit. In contrast, mesocortical dopaminergic transmission appears well preserved in early PD patients.
Key Words: spatial working memory; dopamine D2-receptor; 11C-raclopride positron emission tomography; dorsal caudate; anterior cingulate cortex
Abbreviations: MRI, Magnetic resonance imaging; ROI, region of interest; SWT, spatial working memory task; VMT, visuomotor control task
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Received November 19, 2007. Revised February 21, 2008. Accepted February 25, 2008.
*Present address: Human Brain Research Center, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan