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Prefrontal dopaminergic receptor abnormalities and executive functions in Parkinson's disease.
Hum Brain Mapp. 2013 Jul; 34(7):1591-604.HB

Abstract

The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [(11) C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [(11) C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [(11) C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [(11) C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD.

Authors+Show Affiliations

Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22331665

Citation

Ko, Ji Hyun, et al. "Prefrontal Dopaminergic Receptor Abnormalities and Executive Functions in Parkinson's Disease." Human Brain Mapping, vol. 34, no. 7, 2013, pp. 1591-604.
Ko JH, Antonelli F, Monchi O, et al. Prefrontal dopaminergic receptor abnormalities and executive functions in Parkinson's disease. Hum Brain Mapp. 2013;34(7):1591-604.
Ko, J. H., Antonelli, F., Monchi, O., Ray, N., Rusjan, P., Houle, S., Lang, A. E., Christopher, L., & Strafella, A. P. (2013). Prefrontal dopaminergic receptor abnormalities and executive functions in Parkinson's disease. Human Brain Mapping, 34(7), 1591-604. https://doi.org/10.1002/hbm.22006
Ko JH, et al. Prefrontal Dopaminergic Receptor Abnormalities and Executive Functions in Parkinson's Disease. Hum Brain Mapp. 2013;34(7):1591-604. PubMed PMID: 22331665.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prefrontal dopaminergic receptor abnormalities and executive functions in Parkinson's disease. AU - Ko,Ji Hyun, AU - Antonelli,Francesca, AU - Monchi,Oury, AU - Ray,Nicola, AU - Rusjan,Pablo, AU - Houle,Sylvain, AU - Lang,Anthony E, AU - Christopher,Leigh, AU - Strafella,Antonio P, Y1 - 2012/02/14/ PY - 2011/09/13/received PY - 2011/11/15/revised PY - 2011/11/15/accepted PY - 2012/2/15/entrez PY - 2012/2/15/pubmed PY - 2014/1/28/medline SP - 1591 EP - 604 JF - Human brain mapping JO - Hum Brain Mapp VL - 34 IS - 7 N2 - The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [(11) C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [(11) C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [(11) C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [(11) C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD. SN - 1097-0193 UR - https://www.unboundmedicine.com/medline/citation/22331665/Prefrontal_dopaminergic_receptor_abnormalities_and_executive_functions_in_Parkinson's_disease_ L2 - https://doi.org/10.1002/hbm.22006 DB - PRIME DP - Unbound Medicine ER -