Bilateral deep brain stimulation of the subthalamic nucleus increases pointing error during memory-guided sequential reaching
Deep brain stimulation of the subthalamic nucleus (STN DBS) significantly improves clinical motor symptoms, as well as intensive aspects of movement like velocity and amplitude in patients with Parkinson’s disease (PD). However, the effects of bilateral STN DBS on integrative and coordinative aspects of motor control are equivocal. The aim of this study was to investigate the effects of bilateral STN DBS on integrative and coordinative aspects of movement using a memory-guided sequential reaching task. The primary outcomes were eye and finger velocity and end-point error. We expected that bilateral STN DBS would increase reaching velocity. More importantly, we hypothesized that bilateral STN DBS would increase eye and finger end-point error and this would not simply be the result of a speed accuracy trade-off. Ten patients with PD and bilaterally implanted subthalamic stimulators performed a memory-guided sequential reaching task under four stimulator conditions (DBS-OFF, DBS-LEFT, DBS-RIGHT, and DBS-BILATERAL) over 4 days. DBS-BILATERAL significantly increased eye velocity compared to DBS-OFF, DBS-LEFT, and DBS-RIGHT. It also increased finger velocity compared to DBS-OFF and DBS-RIGHT. DBS-BILATERAL did not change eye end-point error. The novel finding was that DBS-BILATERAL increased finger end-point error compared to DBS-OFF, DBS-LEFT, and DBS-RIGHT even after adjusting for differences in velocity. We conclude that bilateral STN DBS may facilitate basal ganglia–cortical networks that underlie intensive aspects of movement like velocity, but it may disrupt selective basal ganglia–cortical networks that underlie certain integrative and coordinative aspects of movement such as spatial accuracy.
KeywordsSTN DBS Parkinson disease Sequential reach Memory-guided Subthalamic nucleus Deep brain stimulation
The authors thank the participants and our professional colleagues, Maya Cottongim, and Christiane Alford for their important contributions to the successful implementation of this project.
This study was supported by National Institutes of Health (R56NS040902 and R01NS09295001). The sponsors were not involved in the design, conduct, collection, management, analysis, and/or interpretation of the study results and preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of NIH. Statistical analysis: Conducted by FJD.
Compliance with ethical standards
Conflict of interest
FJD, RZT, and LCG have nothing to report. DMC is a Full Professor at Northwestern University and receives a salary, has additional NIH funding (5R01NS074343, 5R01HD075777, 1R01DK110699, 5T15HD074546), and receives honoraria and/or consults for the following: University of Florida, Ohio University Athens, Temple University, Iowa State University, University of Alabama, Birmingham, Oregon Health Sciences Institute, University of Westminster, University of Waterloo, University of Colorado, Denver, Several NIH Study Sections, ACRM, ASNR, University of New Hampshire, University of Minnesota, Movement Disorders Society. LVM has foundation research support from Michael J. Fox Foundation; commercial research support from Medtronic, Inc., US WorldMeds LLC, Pfizer Inc, Boston Scientific, Avanir Pharmaceuticals, Inc., and Adamas Pharmaceuticals, Inc.; is on the scientific advisory board of St. Jude Medical, AbbVie, Inc., and Britannia Pharmaceuticals Ltd.; and consults for St. Jude Medical, AbbVie, Inc., Medtronic, Inc., and Boston Scientific.
- CANTABeclipse® [Cognitive assessment software] Cambridge Cognition (2012) All rights reserved. http://www.cantab.com. Accessed 2014
- Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd ednGoogle Scholar
- Goelz LC, David FJ, Sweeney JA, Vaillancourt DE, Poizner H, Metman LV, Corcos DM (2017) The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson’s disease. Exp Brain Res 235:615–626. https://doi.org/10.1007/s00221-016-4830-2 CrossRefPubMedGoogle Scholar
- Hening W, Harrington DL, Poizner H (2009) Basal ganglia: motor functions of. In: Binder MD, Hirokawa N, Windhorst U (eds) Encyclopedia of Neuroscience. Springer, Berlin, HeidelbergGoogle Scholar
- Hilker R et al (2004) Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 24:7–16. https://doi.org/10.1097/01.WCB.0000092831.44769.09 CrossRefPubMedGoogle Scholar
- Innovative Sports Training (2010) The motion monitor, 8.99 edn. Innovative Sports Training, Inc., ChicagoGoogle Scholar
- Lee D, Henriques DY, Snider J, Song D, Poizner H (2013) Reaching to proprioceptively defined targets in Parkinson’s disease: effects of deep brain stimulation therapy. Neuroscience 244:99–112. https://doi.org/10.1016/j.neuroscience.2013.04.009 CrossRefPubMedPubMedCentralGoogle Scholar
- Nambu A, Tokuno H, Inase M, Takada M (1997) Corticosubthalamic input zones from forelimb representations of the dorsal and ventral divisions of the premotor cortex in the macaque monkey: comparison with the input zones from the primary motor cortex and the supplementary motor area. Neurosci Lett 239:13–16CrossRefPubMedGoogle Scholar
- Northern Digital (2018) Northern Digital Optotrak 3020 Active-marker 3D optical tracking system. Northern Digital Inc., WaterlooGoogle Scholar
- SR Research Eyelink II (2018) SR Research Ltd., OttawaGoogle Scholar
- Swann N et al (2011) Deep brain stimulation of the subthalamic nucleus alters the cortical profile of response inhibition in the beta frequency band: a scalp EEG study in Parkinson’s disease. J Neurosci 31:5721–5729. https://doi.org/10.1523/jneurosci.6135-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
- The MathWorks (2014) Matlab, R2014b edn. The MathWorks, Inc., NatickGoogle Scholar
- Thermo CRS Catalyst 5 Robot Arm (2018) Thermo CRS Ltd., BurlingtonGoogle Scholar
- Vaillancourt DE, Prodoehl J, Sturman MM, Bakay RA, Metman LV, Corcos DM (2006) Effects of deep brain stimulation and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson’s disease. Mov Disord 21:50–58. https://doi.org/10.1002/mds.20672 CrossRefPubMedPubMedCentralGoogle Scholar
- van den Wildenberg WP, van Boxtel GJ, van der Molen MW, Bosch DA, Speelman JD, Brunia CH (2006) Stimulation of the subthalamic region facilitates the selection and inhibition of motor responses in Parkinson’s disease. J Cogn Neurosci 18:626–636. https://doi.org/10.1162/jocn.2006.18.4.626 CrossRefPubMedGoogle Scholar
- Wechsler D (2010) Wechsler Memory Scale—fourth edition (WMS-IV). Flexible approach manual. NCS Pearson Inc, San AntonioGoogle Scholar