Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Sensorimotor subthalamic stimulation restores risk-reward trade-off in Parkinson's disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The biomarker potential of cell-free microRNA from cerebrospinal fluid in Parkinsonian Syndromes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Automatic quantification of micro‐sleep stability in isolated REM sleep behavior disorder and Parkinson's disease

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  5. Genotype-phenotype correlations, dystonia and disease progression in spinocerebellar ataxia type 14

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Accurate and robust whole-head segmentation from magnetic resonance images for individualized head modeling

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Maintenance of muscle strength following a one-year resistance training program in older adults

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Progressive effects of sildenafil on visual processing in rats

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Discrete finger sequences are widely represented in human striatum

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Bart F L van Nuenen
  • Thilo van Eimeren
  • Joyce P M van der Vegt
  • Carsten Buhmann
  • Christine Klein
  • Bastiaan R Bloem
  • Hartwig R Siebner
View graph of relations
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