Shared functional neural substrates in Parkinson's disease and drug-induced parkinsonism: association with dopaminergic depletion

Sci Rep. 2020 Jul 15;10(1):11617. doi: 10.1038/s41598-020-68514-0.

Abstract

While drug-induced parkinsonism (DIP) is mainly caused by blockage of the dopaminergic pathway, multiple neurotransmitter systems besides the dopaminergic system are involved in Parkinson's disease (PD). Therefore, alterations found in both DIP and PD might be manifestations of dopaminergic dysfunction. To prove this hypothesis, we aimed to define the areas commonly involved in DIP and PD and determine whether the overlapping areas were associated with the dopaminergic system. 68 PD patients, 69 DIP patients and 70 age-and sex-matched controls underwent resting-state functional MRI (rsfMRI). Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF were calculated and compared. Afterwards, we compared mean rsfMRI values extracted from the overlapping areas with uptake quantitatively measured on dopamine transporter (DAT) images and neuropsychological test results. Compared to the controls, both PD and DIP patients revealed altered rsfMRI values in the right insular cortex, right temporo-occipital cortex, and cerebellum. Among them, decreased ALFF in the right insular cortex and decreased ReHo in the right occipital cortex were correlated with decreased DAT uptake in the caudate as well as executive, visuospatial, and language function. Increased ReHo in the cerebellum was also correlated with decrease DAT uptake in the posterior and ventral anterior putamen, but not with cognitive function. In conclusion, the insular cortex, occipital cortex, and cerebellum were commonly affected in both PD and DIP patients and might be associated with altered dopaminergic modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / physiopathology
  • Brain Mapping
  • Case-Control Studies
  • Cerebellum / diagnostic imaging
  • Cerebellum / physiopathology
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Models, Neurological
  • Neurons / metabolism*
  • Occipital Lobe / diagnostic imaging
  • Occipital Lobe / physiopathology
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / metabolism*
  • Parkinson Disease / physiopathology*
  • Parkinsonian Disorders / chemically induced*
  • Parkinsonian Disorders / diagnostic imaging
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / physiopathology

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine