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Mapping preclinical compensation in Parkinson's disease: an imaging genomics approach

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  • Bart F L van Nuenen
  • Thilo van Eimeren
  • Joyce P M van der Vegt
  • Carsten Buhmann
  • Christine Klein
  • Bastiaan R Bloem
  • Hartwig R Siebner
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Mutations in the Parkin (PARK2) and PINK1 gene (PARK 6) can cause recessively inherited Parkinson's disease (PD). The presence of a single Parkin or PINK1 mutation is associated with a dopaminergic nigrostriatal dysfunction and conveys an increased risk to develop PD throughout lifetime. Therefore neuroimaging of non-manifesting individuals with a mutant Parkin or PINK1 allele opens up a window for the investigation of preclinical and very early phases of PD in vivo. Here we review how functional magnetic resonance imaging (fMRI) can be used to identify compensatory mechanisms that help to prevent development of overt disease. In two separate experiments, Parkin mutation carriers displayed stronger activation of rostral supplementary motor area (SMA) and right dorsal premotor cortex (PMd) during a simple motor sequence task and anterior cingulate motor area and left rostral PMd during internal movement selection as opposed to externally cued movements. The additional recruitment of the rostral SMA and right rostral PMd during the finger sequence task was also observed in a separate group of nonmanifesting mutation carriers with a single heterozygous PINK1 mutation. Because mutation carriers were not impaired at performing the task, the additional recruitment of motor cortical areas indicates a compensatory mechanism that effectively counteracts the nigrostriatal dysfunction. These first results warrant further studies that use these imaging genomics approach to tap into preclinical compensation of PD. Extensions of this line of research involve fMRI paradigms probing nonmotor brain functions. Additionally, the same fMRI paradigms should be applied to nonmanifesting mutation carriers in genes linked to autosomal dominant PD. This will help to determine how "generically" the human brain compensates for a preclinical dopaminergic dysfunction.
Original languageEnglish
JournalMovement disorders : official journal of the Movement Disorder Society
Volume24 Suppl 2
Issue numberS2
Pages (from-to)S703-10
Number of pages7
DOIs
Publication statusPublished - 2009

    Research areas

  • Antiparkinson Agents, Fingers, Genomics, Humans, Magnetic Resonance Imaging, Movement, Mutation, Parkinson Disease, Protein Kinases, Psychomotor Performance, Ubiquitin-Protein Ligases

ID: 32514145