Functional network differences between unilateral and bilateral deep brain stimulation of the subthalamic nucleus

Brendan Santyr; Alexandre Boutet; Mohamad Abbass; Artur Vetkas; Jürgen Germann; Afis Ajala; Jianwei Qiu; Gavin J B Elias; Can Sarica; Andrew Z Yang; Ibrahim Alhashyan; Suneil K Kalia; Alfonso Fasano; Andres M Lozano

doi:10.1038/s41531-025-01064-2

Functional network differences between unilateral and bilateral deep brain stimulation of the subthalamic nucleus

NPJ Parkinsons Dis. 2025 Jul 17;11(1):215. doi: 10.1038/s41531-025-01064-2.

Authors

Brendan Santyr^#^{1

2}, Alexandre Boutet^#^{1

3}, Mohamad Abbass², Artur Vetkas^{1

4}, Jürgen Germann^{1

5

6}, Afis Ajala⁷, Jianwei Qiu⁷, Gavin J B Elias¹, Can Sarica¹, Andrew Z Yang¹, Ibrahim Alhashyan⁸, Suneil K Kalia^{1

5

6}, Alfonso Fasano^#^{4

6

8}, Andres M Lozano^#^{9

10

11}

Affiliations

¹ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
² Department of Clinical Neurological Sciences, Western University, London, ON, Canada.
³ Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
⁴ Department of Clinical Neuroscience, Neurosurgery, Karolinska Institute, Stockholm, Sweden.
⁵ Krembil Brain Institute, Toronto, ON, Canada.
⁶ Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada.
⁷ GE Research, Niskayuna, NY, USA.
⁸ Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital-UHN. Division of Neurology, University of Toronto, Toronto, ON, Canada.
⁹ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada. lozano@uhnresearch.ca.
¹⁰ Krembil Brain Institute, Toronto, ON, Canada. lozano@uhnresearch.ca.
¹¹ Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada. lozano@uhnresearch.ca.

^# Contributed equally.

Abstract

Unilateral versus bilateral implantation is a critical surgical consideration for deep brain stimulation in Parkinson's disease; however, the differing therapeutic effects remain incompletely understood. Using functional magnetic resonance imaging during active stimulation, we show that bilateral stimulation reinforces the recruitment of key motor hubs while reducing non-motor responses seen with unilateral stimulation and correlates with improved outcomes. This suggests a potential mechanistic basis for better motor function following bilateral stimulation.

Abstract

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