Abstract
People with Parkinson’s disease (PD) exhibit an increase in fixational saccades during the preparatory period prior to target onset in the antisaccade task and this increase is related to an increase in prosaccade errors in the antisaccade task. It was previously shown that bilateral, but not unilateral, subthalamic nucleus deep brain stimulation (STN DBS) in people with PD further increases the prosaccade error rate on the antisaccade task. We investigated whether bilateral STN DBS also increases the number of fixational saccades in the preparatory period of the antisaccade task and if this increase in the number of fixational saccades is related to prosaccade errors. We found that: (1) there were a greater number of fixational saccades during the preparatory period of the antisaccade task during bilateral STN DBS compared to no STN DBS (p < 0.001), unilateral STN DBS (p < 0.001), and healthy controls (p = 0.02), and (2) the increase in the number of fixational saccades increased the probability of a prosaccade error for the antisaccade task during bilateral STN DBS (p = 0.005). This association between number of fixational saccades and probability of a prosaccade error was similar across no STN DBS, unilateral stimulation, and healthy controls. In addition, we found that the proportion of express prosaccade errors and prosaccade error latency were similar across stimulation conditions. We propose that bilateral STN DBS disrupts the integrated activity of cortico-basal ganglia-collicular processes underlying antisaccade preparation and that this disruption manifests as an increase in both fixational saccades and prosaccade error rate.
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Acknowledgements
The authors thank the participants and our professional colleagues, Jay Pillai and Christiane Alford, for their important contributions to the successful implementation of this project.
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This study was supported by the National Institutes of Health (R56NS040902 and R01NS09295001A1). 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.
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LCG was responsible for research project conception, organization, and execution; involved with reviewing and critiquing the statistical analysis; responsible for writing first draft of manuscript. MLC was involved in research project execution, including data processing and interpretation, and the review and critique of the statistical analysis and manuscript. LVM was responsible for research project execution and involved with review and critique of the statistical analysis and manuscript. DMC was responsible for research project conception and organization and for the review and critique of the statistical analysis and manuscript. FJD was responsible for research project concept development, organization, and execution; responsible for statistical analysis design and execution, and responsible for review and critique of the manuscript.
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LCG and FJD received Grant support from NIH. LCG, MLC, and FJD have no conflict of interest 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.
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Goelz, L.C., Cottongim, M., Metman, L.V. et al. Bilateral subthalamic nucleus deep brain stimulation increases fixational saccades during movement preparation: evidence for impaired preparatory set. Exp Brain Res 237, 2841–2851 (2019). https://doi.org/10.1007/s00221-019-05636-6
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DOI: https://doi.org/10.1007/s00221-019-05636-6