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Task specific influences of Parkinson's disease on the striato-thalamo-cortical and cerebello-thalamo-cortical motor circuitries.
Full Abstract
The motor deficits in Parkinson's disease (PD) have been primarily associated with internally guided (IG), but not externally guided (EG), tasks. This study investigated the functional mechanisms underlying this phenomenon using genetically-matched twins. Functional magnetic resonance images were obtained from a monozygotic twin pair discordant for clinical PD. Single-photon emission computed tomography neuroimaging using [(123)I](-)-2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane confirmed their disease-discordant status by demonstrating a severe loss of transporter binding in the PD-twin, whereas the non-PD-twin was normal. Six runs of functional magnetic resonance imaging (fMRI) data were acquired from each twin performing EG and IG right-hand finger sequential tasks. The percentage of voxels activated in each of several regions of interest (ROI) was calculated. Multiple analysis of variance was used to compare each twin's activity in ROIs constituting the striato-thalamo-cortical motor circuits [basal ganglia (BG)-cortical circuitry, but including the globus pallidus/putamen, thalamus, supplementary motor area, and primary motor cortex] and cerebello-thalamo-cortical circuits (cerebellar-cortical circuitry, including the cerebellum, thalamus, somatosensory cortex, and lateral premotor cortex). During the EG task, there were no significant differences between the twins in bilateral BG-cortical pathways, either basally or after levodopa, whereas the PD-twin had relatively increased activity in the cerebellar-cortical pathways basally that was normalized by levodopa. During the IG task, the PD-twin had less activation than the non-PD-twin in ROIs of the bilateral BG-cortical and cerebellar-cortical pathways. Levodopa normalized the hypoactivation in the contralateral BG-cortical pathway, but "over-corrected" the activation in the ipsilateral BG-cortical and bilateral cerebellar-cortical pathways. In this first fMRI study of twins discordant for PD, the data support the hypothesis that BG-cortical and cerebellar-cortical pathways are task-specifically influenced by PD. The levodopa-induced "over-activation" of BG-cortical and cerebellar-cortical pathways, and its relevance to both compensatory changes in PD and the long-term effects of levodopa in PD, merit further exploration.
Author information
Author/s: Lewis, M M (MM); Slagle, C G (CG); Smith, A B (AB); Truong, Y (Y); Bai, P (P); McKeown, M J (MJ); Mailman, R B (RB); Belger, A (A); Huang, X (X);
Affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599-7125, USA.
Grants: AG 21491 (Agency:NIA NIH HHS) ; K23 AG021491-01 (Agency:NIA NIH HHS) ; K23 AG021491-02 (Agency:NIA NIH HHS) ; K23 AG021491-03 (Agency:NIA NIH HHS) ; K23 AG021491-04 (Agency:NIA NIH HHS) ; K23 AG021491-05 (Agency:NIA NIH HHS) ; M01 RR000046-441262 (Agency:NCRR NIH HHS) ; M01 RR000046-451262 (Agency:NCRR NIH HHS) ; M01 RR000046-467435 (Agency:NCRR NIH HHS) ; MH 058251 (Agency:NIMH NIH HHS) ; R01 MH058251-05 (Agency:NIMH NIH HHS) ; RR 00046 (Agency:NCRR NIH HHS)
Journal and publication information
Publication Type: Case Reports; Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Twin Study
Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)
Reference: 2007-Jun; vol 147 (issue 1) : pp 224-35
Dates: Created 2007/06/11; Completed 2007/10/16; Revised 2008/11/20;
PMID: 17499933, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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