Abstract

We mapped the distribution of atrophy in Parkinson's Disease (PD) using MRI and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

Article and author information

Author details

  1. Yashar Zeighami

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Miguel Ulla

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Yasser Iturria-Medina

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Mahsa Dadar

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Yu Zhang

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Kevin Michel-Herve Larcher

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Vladimir Fonov

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Alan C Evans

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Douglas Louis Collins

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Alain Dagher

    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada
    For correspondence
    alain.dagher@mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: For the Parkinson's Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data)Each participating PPMI site received approval from a local research ethics committee before study initiation, and obtained written informed consent from all subjects participating in the study.For the resting state fMRI data collected in our lab, We acquired resting state fMRI in 51 healthy, right-handed volunteers.The experimental protocol was reviewed and approved by Research Ethics Board of Montreal Neurological Institute. All subjects gave informed consent.

Copyright

© 2015, Zeighami 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

  • 6,963
    views
  • 1,368
    downloads
  • 194
    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. Yashar Zeighami
  2. Miguel Ulla
  3. Yasser Iturria-Medina
  4. Mahsa Dadar
  5. Yu Zhang
  6. Kevin Michel-Herve Larcher
  7. Vladimir Fonov
  8. Alan C Evans
  9. Douglas Louis Collins
  10. Alain Dagher
(2015)
Network structure of brain atrophy in de novo Parkinson's Disease
eLife 4:e08440.
https://doi.org/10.7554/eLife.08440

Share this article

https://doi.org/10.7554/eLife.08440

Further reading

    1. Neuroscience
    Lian Hollander-Cohen, Omer Cohen ... Berta Levavi-Sivan
    Research Article

    Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here, we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.

    1. Neuroscience
    Mina Mišić, Noah Lee ... Herta Flor
    Research Article

    Chronic back pain (CBP) is a global health concern with significant societal and economic burden. While various predictors of back pain chronicity have been proposed, including demographic and psychosocial factors, neuroimaging studies have pointed to brain characteristics as predictors of CBP. However, large-scale, multisite validation of these predictors is currently lacking. In two independent longitudinal studies, we examined white matter diffusion imaging data and pain characteristics in patients with subacute back pain (SBP) over 6- and 12-month periods. Diffusion data from individuals with CBP and healthy controls (HC) were analyzed for comparison. Whole-brain tract-based spatial statistics analyses revealed that a cluster in the right superior longitudinal fasciculus (SLF) tract had larger fractional anisotropy (FA) values in patients who recovered (SBPr) compared to those with persistent pain (SBPp), and predicted changes in pain severity. The SLF FA values accurately classified patients at baseline and follow-up in a third publicly available dataset (Area under the Receiver Operating Curve ~0.70). Notably, patients who recovered had FA values larger than those of HC suggesting a potential role of SLF integrity in resilience to CBP. Structural connectivity-based models also classified SBPp and SBPr patients from the three data sets (validation accuracy 67%). Our results validate the right SLF as a robust predictor of CBP development, with potential for clinical translation. Cognitive and behavioral processes dependent on the right SLF, such as proprioception and visuospatial attention, should be analyzed in subacute stages as they could prove important for back pain chronicity.