Subthalamic stimulation impairs stopping of ongoing movements

Author:

Lofredi Roxanne12ORCID,Auernig Georg Cem1,Irmen Friederike1ORCID,Nieweler Johanna3,Neumann Wolf-Julian14ORCID,Horn Andreas1ORCID,Schneider Gerd-Helge5,Kühn Andrea A14678

Affiliation:

1. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany

2. Berlin Institute of Health (BIH), Berlin, Germany

3. Department of Neurology, Universitätsmedizin Göttingen, Göttingen, Germany

4. Bernstein Center for Computational Neuroscience, Humboldt-Universität, Berlin, Germany

5. Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany

6. NeuroCure, Exzellenzcluster, Charité-Universitätsmedizin Berlin, Berlin, Germany

7. DZNE, German center for neurodegenerative diseases, Berlin, Germany

8. Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany

Abstract

Abstract The subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In Parkinson’s disease, subthalamic deep brain stimulation improves movement initiation and velocity, but its effect on stopping of ongoing movement is unknown. Here, we examine the relation between movement stopping and connectivity of stimulation volumes to the stopping network. Stop and go times were collected in 17 patients with Parkinson’s disease on and off subthalamic stimulation during visually cued initiation and termination of continuous, rotational movements. Deep brain stimulation contacts were localized; the stimulation volume computed and connectivity profiles estimated using an openly available, normative structural connectome. Subthalamic stimulation significantly increased stop times, which correlated with the connectivity of the stimulation volume to presupplementary motor area and inferior frontal gyrus of the right hemisphere. The robustness of this finding was validated using three separate analysis streams: voxel-wise whole-brain connectivity, region of interest connectivity and a tract-centred method. Our study sheds light on the role of the fronto-subthalamic inhibitory triangle in stopping of ongoing movements and may inspire circuit based adaptive stimulation strategies for control of stopping impairment, possibly reflected in stimulation-induced dyskinesia.

Funder

Berlin Institute of Health

German Research Council

Deutsche Forschungsgemeinschaft

German Research Foundation

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

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