Resting state functional connectivity of the striatum in Parkinson's disease

Document Type

Article

Abstract

Classical accounts of the pathophysiology of Parkinson's disease have emphasized degeneration of dopaminergic nigrostriatal neurons with consequent dysfunction of cortico-striatal-thalamic loops. In contrast, post-mortem studies indicate that pathological changes in Parkinson's disease (Lewy neurites and Lewy bodies) first appear primarily in the lower brainstem with subsequent progression to more rostral parts of the neuraxis. The nigrostriatal and histological perspectives are not incompatible, but they do emphasize different anatomical structures. To address the question of which brain structures are functionally most affected by Parkinson's disease, we performed a resting-state functional magnetic resonance imaging study focused on striatal functional connectivity. We contrasted 13 patients with advanced Parkinson's disease versus 19 age-matched control subjects, using methodology incorporating scrupulous attention to minimizing the effects of head motion during scanning. The principal finding in the Parkinson's disease group was markedly lower striatal correlations with thalamus, midbrain, pons and cerebellum. This result reinforces the importance of the brainstem in the pathophysiology of Parkinson's disease. Focally altered functional connectivity also was observed in sensori-motor and visual areas of the cerebral cortex, as well the supramarginal gyrus. Striatal functional connectivity with the brainstem was graded (posterior putamen > anterior putamen > caudate), in both patients with Parkinson's disease and control subjects, in a manner that corresponds to well-documented gradient of striatal dopaminergic function loss in Parkinson's disease. We hypothesize that this gradient provides a clue to the pathogenesis of Parkinson's disease.

Medical Subject Headings

Aged; Brain Mapping; Case-Control Studies; Corpus Striatum (blood supply, pathology, physiopathology); Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways (blood supply, physiology); Oxygen (blood); Parkinson Disease (diagnostic imaging, pathology); Radionuclide Imaging; Rest (physiology); Severity of Illness Index; Statistics as Topic

Publication Date

12-1-2012

Publication Title

Brain : a journal of neurology

E-ISSN

1460-2156

Volume

135

Issue

Pt 12

First Page

3699

Last Page

711

PubMed ID

23195207

Digital Object Identifier (DOI)

10.1093/brain/aws281

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