Parkinson’s disease as a system-level disorder

Daniele Caligiore*, Rick C. Helmich, Mark Hallett, Ahmed A. Moustafa, Lars Timmermann, Ivan Toni, Gianluca Baldassarre

*Corresponding author for this work

Research output: Contribution to journalReview articleResearchpeer-review

110 Citations (Scopus)
33 Downloads (Pure)


Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson’s disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson’s disease as caused by the dysfunction of the entire basal ganglia–cortex–cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson’s disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

Original languageEnglish
Article number16025
Journalnpj Parkinson's Disease
Issue number1
Publication statusPublished - 1 Dec 2016
Externally publishedYes


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