Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson's disease

  1. Roxanne Lofredi  Is a corresponding author
  2. Wolf-Julian Neumann
  3. Antje Bock
  4. Andreas Horn
  5. Julius Huebl
  6. Sandy Siegert
  7. Gerd-Helge Schneider
  8. Joachim K Krauss
  9. Andrea A Kühn  Is a corresponding author
  1. Charité - Universitätsmedizin Berlin, Germany
  2. Medizinische Hochschule Hannover, Germany

Abstract

Gamma synchronization increases during movement and scales with kinematic parameters. Here, disease-specific characteristics of this synchronization and the dopamine-dependence of its scaling in Parkinson's disease are investigated. In 16 patients undergoing deep brain stimulation surgery, movements of different velocities revealed that subthalamic gamma power peaked in the sensorimotor part of the subthalamic nucleus, correlated positively with maximal velocity and negatively with symptom severity. These effects relied on movement-related bursts of transient synchrony in the gamma band. The gamma burst rate highly correlated with averaged power, increased gradually with larger movements and correlated with symptom severity. In the dopamine-depleted state, gamma power and burst rate significantly decreased, particularly when peak velocity was slower than ON medication. Burst amplitude and duration were unaffected by the medication state. We propose that insufficient recruitment of fast gamma bursts during movement may underlie bradykinesia as one of the cardinal symptoms in Parkinson's disease.

Article and author information

Author details

  1. Roxanne Lofredi

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    For correspondence
    roxanne.lofredi@charite.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1845-8250
  2. Wolf-Julian Neumann

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6758-9708
  3. Antje Bock

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Andreas Horn

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Julius Huebl

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Sandy Siegert

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Gerd-Helge Schneider

    Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Joachim K Krauss

    Department of Neurosurgery, Medizinische Hochschule Hannover, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Andrea A Kühn

    Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    For correspondence
    andrea.kuehn@charite.de
    Competing interests
    The authors declare that no competing interests exist.

Funding

Deutsche Forschungsgemeinschaft (DFG KFO247)

  • Andrea A Kühn

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All participants provided written informed conset which was approved by the local review boeards of the Charité - Universitätsmedizin Berlin and Hannover Medical School and in accordance with the standards set by the Declaration of Helsinki (EA2/071/08).

Copyright

© 2018, Lofredi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,014
    views
  • 437
    downloads
  • 138
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Roxanne Lofredi
  2. Wolf-Julian Neumann
  3. Antje Bock
  4. Andreas Horn
  5. Julius Huebl
  6. Sandy Siegert
  7. Gerd-Helge Schneider
  8. Joachim K Krauss
  9. Andrea A Kühn
(2018)
Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson's disease
eLife 7:e31895.
https://doi.org/10.7554/eLife.31895

Share this article

https://doi.org/10.7554/eLife.31895

Further reading

    1. Medicine
    2. Neuroscience
    Tomohiro Umeda, Ayumi Sakai ... Takami Tomiyama
    Research Article

    Neurodegenerative diseases are age-related disorders characterized by the cerebral accumulation of amyloidogenic proteins, and cellular senescence underlies their pathogenesis. Thus, it is necessary for preventing these diseases to remove toxic proteins, repair damaged neurons, and suppress cellular senescence. As a source for such prophylactic agents, we selected zizyphi spinosi semen (ZSS), a medicinal herb used in traditional Chinese medicine. Oral administration of ZSS hot water extract ameliorated Aβ and tau pathology and cognitive impairment in mouse models of Alzheimer’s disease and frontotemporal dementia. Non-extracted ZSS simple crush powder showed stronger effects than the extract and improved α-synuclein pathology and cognitive/motor function in Parkinson’s disease model mice. Furthermore, when administered to normal aged mice, the ZSS powder suppressed cellular senescence, reduced DNA oxidation, promoted brain-derived neurotrophic factor expression and neurogenesis, and enhanced cognition to levels similar to those in young mice. The quantity of known active ingredients of ZSS, jujuboside A, jujuboside B, and spinosin was not proportional to the nootropic activity of ZSS. These results suggest that ZSS simple crush powder is a promising dietary material for the prevention of neurodegenerative diseases and brain aging.

    1. Medicine
    Hyun Beom Song, Laura Campello ... Anand Swaroop
    Research Advance

    Inherited retinal degenerations (IRDs) constitute a group of clinically and genetically diverse vision-impairing disorders. Retinitis pigmentosa (RP), the most common form of IRD, is characterized by gradual dysfunction and degeneration of rod photoreceptors, followed by the loss of cone photoreceptors. Recently, we identified reserpine as a lead molecule for maintaining rod survival in mouse and human retinal organoids as well as in the rd16 mouse, which phenocopy Leber congenital amaurosis caused by mutations in the cilia-centrosomal gene CEP290 (Chen et al., 2023). Here, we show the therapeutic potential of reserpine in a rhodopsin P23H rat model of autosomal dominant RP. At postnatal day (P) 68, when males and females are analyzed together, the reserpine-treated rats exhibit higher rod-derived scotopic b-wave amplitudes compared to the controls with little or no change in scotopic a-wave or cone-derived photopic b-wave. Interestingly, the reserpine-treated female rats display enhanced scotopic a- and b-waves and photopic b-wave responses at P68, along with a better contrast threshold and increased outer nuclear layer thickness. The female rats demonstrate better preservation of both rod and cone photoreceptors following reserpine treatment. Retinal transcriptome analysis reveals sex-specific responses to reserpine, with significant upregulation of phototransduction genes and proteostasis-related pathways, and notably, genes associated with stress response. This study builds upon our previously reported results reaffirming the potential of reserpine for gene-agnostic treatment of IRDs and emphasizes the importance of biological sex in retinal disease research and therapy development.