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

• Published in: Brain (London, England : 1878) Vol. 135; no. 12; pp. 3699 - 3711
• Main Authors: Hacker, Carl D., Perlmutter, Joel S., Criswell, Susan R., Ances, Beau M., Snyder, Abraham Z.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2012
• Subjects: Aged; Biological and medical sciences; Brain Mapping; Case-Control Studies; Corpus Striatum - blood supply; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Neural Pathways - blood supply; Neural Pathways - physiology; Neurology; Original; Oxygen - blood; Parkinson Disease - diagnostic imaging; Parkinson Disease - pathology; Radionuclide Imaging; Rest - physiology; Severity of Illness Index; Statistics as Topic; functional MRI; brainstem; functional reorganization; striatum; Parkinson’s disease; Nervous system diseases; Functional reorganization; Parkinson's disease; Central nervous system disease; Parkinson disease; Degenerative disease; Nuclear magnetic resonance imaging; Cerebral disorder; Extrapyramidal syndrome
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/aws281

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.