Brain

This Article Full Text FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (82) Request Permissions Disclaimer Google Scholar Articles by Rakshi, J. S. Articles by Brooks, D. J. Search for Related Content PubMed PubMed Citation Articles by Rakshi, J. S. Articles by Brooks, D. J. Social Bookmarking          What's this?

Brain, Vol. 122, No. 9, 1637-1650, September 1999
© 1999 Oxford University Press

Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [¹⁸F]dopa-PET study

J. S. Rakshi¹, T. Uema¹, K. Ito^1,4, D. L. Bailey¹, P. K. Morrish¹, J. Ashburner², A. Dagher¹, I. H. Jenkins¹, K. J. Friston² and D. J. Brooks^1,3

¹ MRC Cyclotron Unit, Hammersmith Hospital, ² The Wellcome Department of Cognitive Neurology and ³ Department of Clinical Neurology, Institute of Neurology, London, UK and ⁴ Department of Biofunctional Research, National Institute for Longevity Sciences, Obu, Japan

Correspondence to: Dr James S. Rakshi, MRC Cyclotron Unit, Hammersmith Hospital, Du Cane Rd, London W12 ONN, UK E-mail: james{at}wren.rpms.ac.uk

We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical parametric mapping (SPM) to 3D [¹⁸F]dopa-PET. Data from seven early hemi-Parkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [¹⁸F]dopa influx rate constant (K_i^o) were generated for each subject from dynamic 3D [¹⁸F]dopa datasets and transformed into standard stereotactic space. Significant changes in mean voxel [¹⁸F]dopa K_i^o values between the normal control group and each Parkinson's disease group were localized with SPM. Conventional region of interest analysis was also applied to comparable regions on the untransformed image datasets. In early left hemi-Parkinson's disease, significant extrastriatal increases in [¹⁸F]dopa K_i^o were observed in the left anterior cingulate gyrus and the dorsal midbrain region (P < 0.05, corrected) along with decreases in striatal [¹⁸F]dopa K_i^o. In advanced Parkinson's disease, significant extrastriatal decreases in [¹⁸F]dopa K_i^o were observed in the ventral and dorsal midbrain regions (P < 0.05, corrected). No significant changes in [¹⁸F]dopa K_i^o were observed in the anterior cingulate region. In a direct comparison between the early and late Parkinson's disease groups, we observed relative [¹⁸F]dopa K_i^o reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [¹⁸F]dopa K_i^o reductions. Similiar results were found with a region of interest approach, on non-transformed data, except for the focal midbrain [¹⁸F]dopa K_i^o increase seen in early Parkinson's disease. In conclusion, using SPM with [¹⁸F]dopa-PET, we have objectively localized changes in extrastriatal, pre-synaptic dopaminergic function in Parkinson's disease. The significance of the increased dopaminergic activity of anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [¹⁸F]dopa signal in dorsal midbrain and pontine regions suggests that [¹⁸F]dopa is taken up by serotonergic and noradrenergic neurons which also degenerate in advanced Parkinson's disease. This suggests, therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder.

Parkinson's disease; 3D [¹⁸F]dopa; focal changes; extrastriatal; progression

AADC = aromatic amino acid decarboxylase activity; COMT = catechol-O-methyl transferase; K_i^o = influx rate constant; MTGA = multiple time graphical analysis; rCBF = regional cerebral blood flow; SPM = statistical parametric mapping; UPDRS = Unified Parkinson's Disease Rating Scale

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				P. Marklund, A. Larsson, E. Elgh, J. Linder, K. A. Riklund, L. Forsgren, and L. Nyberg Temporal dynamics of basal ganglia under-recruitment in Parkinson's disease: transient caudate abnormalities during updating of working memory Brain, February 1, 2009; 132(2): 336 - 346. [Abstract] [Full Text] [PDF]

				M. Argyelan, M. Carbon, M.-F. Ghilardi, A. Feigin, P. Mattis, C. Tang, V. Dhawan, and D. Eidelberg Dopaminergic Suppression of Brain Deactivation Responses during Sequence Learning J. Neurosci., October 15, 2008; 28(42): 10687 - 10695. [Abstract] [Full Text] [PDF]

				J. B. Rowe, L. Hughes, B. C. P. Ghosh, D. Eckstein, C. H. Williams-Gray, S. Fallon, R. A. Barker, and A. M. Owen Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition Brain, August 1, 2008; 131(8): 2094 - 2105. [Abstract] [Full Text] [PDF]

				N. Sawamoto, P. Piccini, G. Hotton, N. Pavese, K. Thielemans, and D. J. Brooks Cognitive deficits and striato-frontal dopamine release in Parkinson's disease Brain, May 1, 2008; 131(5): 1294 - 1302. [Abstract] [Full Text] [PDF]

				S. Hirano, K. Asanuma, Y. Ma, C. Tang, A. Feigin, V. Dhawan, M. Carbon, and D. Eidelberg Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson's Disease J. Neurosci., April 16, 2008; 28(16): 4201 - 4209. [Abstract] [Full Text] [PDF]

				C. H. Williams-Gray, A. Hampshire, R. A. Barker, and A. M. Owen Attentional control in Parkinson's disease is dependent on COMT val158met genotype Brain, February 1, 2008; 131(2): 397 - 408. [Abstract] [Full Text] [PDF]

				C. H. Williams-Gray, A. Hampshire, T. W. Robbins, A. M. Owen, and R. A. Barker Catechol O-Methyltransferase val158met Genotype Influences Frontoparietal Activity during Planning in Patients with Parkinson's Disease J. Neurosci., May 2, 2007; 27(18): 4832 - 4838. [Abstract] [Full Text] [PDF]

				A. Vallesi, T. Shallice, and V. Walsh Role of the Prefrontal Cortex in the Foreperiod Effect: TMS Evidence for Dual Mechanisms in Temporal Preparation Cereb Cortex, February 1, 2007; 17(2): 466 - 474. [Abstract] [Full Text] [PDF]

				K. Van Laere, C. Casteels, L. De Ceuninck, B. Vanbilloen, A. Maes, L. Mortelmans, W. Vandenberghe, A. Verbruggen, and R. Dom Dual-Tracer Dopamine Transporter and Perfusion SPECT in Differential Diagnosis of Parkinsonism Using Template-Based Discriminant Analysis J. Nucl. Med., March 1, 2006; 47(3): 384 - 392. [Abstract] [Full Text] [PDF]

				P. Piccini, N. Pavese, P. Hagell, J. Reimer, A. Bjorklund, W. H. Oertel, N. P. Quinn, D. J. Brooks, and O. Lindvall Factors affecting the clinical outcome after neural transplantation in Parkinson's disease Brain, December 1, 2005; 128(12): 2977 - 2986. [Abstract] [Full Text] [PDF]

				X.-B. Pan, T. G. Wright, F. J. Leong, R. A. McLaughlin, J. M. Declerck, and D. H.S. Silverman Improving Influx Constant and Ratio Estimation in FDOPA Brain PET Analysis for Parkinson's Disease J. Nucl. Med., October 1, 2005; 46(10): 1737 - 1744. [Abstract] [Full Text] [PDF]

				A L Cheesman, R A Barker, S J G Lewis, T W Robbins, A M Owen, and D J Brooks Lateralisation of striatal function: evidence from 18F-dopa PET in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1204 - 1210. [Abstract] [Full Text] [PDF]

				C. Scherfler, K. Seppi, E. Donnemiller, G. Goebel, C. Brenneis, I. Virgolini, G. K. Wenning, and W. Poewe Voxel-wise analysis of [123I]{beta}-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease Brain, July 1, 2005; 128(7): 1605 - 1612. [Abstract] [Full Text] [PDF]

				P. Remy, M. Doder, A. Lees, N. Turjanski, and D. Brooks Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system Brain, June 1, 2005; 128(6): 1314 - 1322. [Abstract] [Full Text] [PDF]

				V. Bouilleret, F. Semah, A. Biraben, D. Taussig, F. Chassoux, A. Syrota, and M.-J. Ribeiro Involvement of the Basal Ganglia in Refractory Epilepsy: An 18F-Fluoro-L-DOPA PET Study Using 2 Methods of Analysis J. Nucl. Med., March 1, 2005; 46(3): 540 - 547. [Abstract] [Full Text] [PDF]

				A. L. Whone, D. L. Bailey, P. Remy, N. Pavese, and D. J. Brooks A Technique for Standardized Central Analysis of 6-18F-Fluoro-L-DOPA PET Data from a Multicenter Study J. Nucl. Med., July 1, 2004; 45(7): 1135 - 1145. [Abstract] [Full Text] [PDF]

				C. Scherfler, N. L. Khan, N. Pavese, L. Eunson, E. Graham, A. J. Lees, N. P. Quinn, N. W. Wood, D. J. Brooks, and P. P. Piccini Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism Brain, June 1, 2004; 127(6): 1332 - 1342. [Abstract] [Full Text] [PDF]

				J. E. Ahlskog Slowing Parkinson's disease progression: Recent dopamine agonist trials Neurology, February 11, 2003; 60(3): 381 - 389. [Abstract] [Full Text] [PDF]

				M Ghaemi, R Hilker, J Rudolf, J Sobesky, and W-D Heiss Differentiating multiple system atrophy from Parkinson's disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging J. Neurol. Neurosurg. Psychiatry, November 1, 2002; 73(5): 517 - 523. [Abstract] [Full Text] [PDF]

				K. Ito, A. Nagano-Saito, T. Kato, Y. Arahata, A. Nakamura, Y. Kawasumi, K. Hatano, Y. Abe, T. Yamada, T. Kachi, et al. Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[18F]fluoro-L-dopa PET study Brain, June 1, 2002; 125(6): 1358 - 1365. [Abstract] [Full Text] [PDF]

				D. J. Doudet Radionuclide Imaging in Parkinson's Disease: Diagnosis, Treatment, and Disease Progression Journal of Pharmacy Practice, August 1, 2001; 14(4): 341 - 350. [Abstract] [PDF]

				V. Kaasinen, E. Nurmi, A. Bruck, O. Eskola, J. Bergman, O. Solin, and J. O. Rinne Increased frontal [18F]fluorodopa uptake in early Parkinson's disease: sex differences in the prefrontal cortex Brain, June 1, 2001; 124(6): 1125 - 1130. [Abstract] [Full Text] [PDF]

				M. T. M. Hu, S. J. White, A. H. Herlihy, K. R. Chaudhuri, J. V. Hajnal, and D. J. Brooks A comparison of 18F-dopa PET and inversion recovery MRI in the diagnosis of Parkinson's disease Neurology, May 8, 2001; 56(9): 1195 - 1200. [Abstract] [Full Text] [PDF]

				A. Dagher, A. M. Owen, H. Boecker, and D. J. Brooks The role of the striatum and hippocampus in planning: A PET activation study in Parkinson's disease Brain, May 1, 2001; 124(5): 1020 - 1032. [Abstract] [Full Text] [PDF]

Online ISSN 1460-2156 - Print ISSN 0006-8950

Copyright © 2009 Guarantors of Brain

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics