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Author Notes:

Abraham Mathai, Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA, Tel: +1-404-727-7238, abraham.mathai@emory.edu,

OR Yoland Smith, PhD, Yerkes National Primate Research Center, 954 Gatewood Rd NE, Atlanta, GA 30329, USA, Tel: +1-404-727-7519, ysmit01@emory.edu.

A.M. and Y.S. designed the study; A.M. performed the experiments and analyzed the data; T.W. provided expert guidance throughout the project; A.M., T.W. and Y.S. wrote the manuscript.

The authors would like to thank Mr. Jean-Francois Paré and Ms. Susan Jenkins for their valuable technical assistance.

None of the authors has a conflict of interest.

A.M. is a doctoral candidate employed by Emory University’s PhD Neuroscience program, and has owned a non-controlling stake in OPKO Health, Inc.

T.W. is employed by Emory University (School of Medicine, Dept. of Neurology), and is a member of the scientific advisory board of the Bachmann-Strauss Foundation; During the last year, he has received a speaker’s honorarium from SUNY Buffalo, and has been awarded grants from the National Institutes of Health, and the Michael J. Fox Foundation.

Y.S. is employed by Emory University (School of Medicine, Dept. of Neurology). During the last year, he has received honoraria for his services, as a consultant and reviewer of grant proposals, from the National Institutes of Health, Skolkovo Foundation (Russia), CHDI Foundation (USA) and AERES Foundation (France); and has been awarded grants from the National Institutes of Health, and the Michael J. Fox Foundation.

Subjects:

Research Funding:

This work was supported by NIH grants P50 NS071669 (Udall Center grant, T.W., Y.S.) and R01 NS037948 (Y.S.); and by the National Center for Research Resources P51RR000165; and the Office of Research Infrastructure Programs / OD P51OD011132 to the Yerkes National Primate Research Center.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • deep brain stimulation
  • Parkinson's disease
  • fibers of passage
  • globus pallidus
  • antidromic
  • DEEP-BRAIN-STIMULATION
  • PARKINSONS-DISEASE
  • BASAL GANGLIA
  • ELECTRICAL-STIMULATION
  • GLOBUS-PALLIDUS
  • IMPROVEMENT
  • PRINCIPLES
  • ELEMENTS
  • TRIAL

More Than Meets the Eye-Myelinated Axons Crowd the Subthalamic Nucleus

Tools:

Journal Title:

Movement Disorders

Volume:

Volume 28, Number 13

Publisher:

, Pages 1811-1815

Type of Work:

Article | Post-print: After Peer Review

Abstract:

High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a successful treatment for patients with advanced Parkinson's disease (PD). Although its exact mechanism of action is unknown, it is currently believed that the beneficial effects of the stimulation are mediated either by alleviating pathological basal ganglia output patterns of activity or by activation of the axons of passage that arise from the cerebral cortex and other sources. In this study, we show that the anatomical composition of the primate STN provides a substrate through which DBS may elicit widespread changes in brain activity via stimulation of fibers of passage. Using quantitative high-resolution electron microscopy, we found that the primate STN is traversed by numerous myelinated axons, which occupy as much as 45% of its sensorimotor territory and 36% of its associative region. In comparison, myelinated axons occupy only 27% of the surface areas of the sensorimotor and associative regions of the internal segment of the globus pallidus (GPi), another target for therapeutic DBS in PD. We also noted that myelinated axons in the STN, on average, have a larger diameter than those in GPi, which may render them more susceptible to electrical stimulation. Because axons are more excitable than other neuronal elements, our findings support the hypothesis that STN DBS, even when carried out entirely within the confines of the nucleus, mediates some of its effects by activating myelinated axons of passage.

Copyright information:

© 2013 Movement Disorder Society.

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