A new study from researchers at UHN's Krembil Brain Institute (KBI) reveals deep brain stimulation (DBS) treats Parkinson disease (PD) by activating brain-wide networks, and how results may differ depending on the area of the brain where stimulation is applied. The findings could help clinicians choose the most appropriate treatment target for each patient, leading to more personalized care. 

DBS is a well-established treatment for the movement symptoms of Parkinson disease. It works by delivering small electrical pulses to specific areas deep within the brain through implanted electrodes. In Parkinson disease, these electrodes are most commonly placed in one of two brain regions: the subthalamic nucleus (STN) or the globus pallidus internus (GPi). While both targets can effectively improve symptoms, outcomes can vary depending on which area is stimulated. Until now, limited understanding of how DBS works and why these targets produce different effects has made it difficult to determine which approach may be best for individual patients. 

To better understand how DBS works, the KBI team used a specialized magnetic resonance imaging (MRI) technique called functional MRI (fMRI) to measure brain activity while participants were receiving DBS. The researchers studied 36 people with PD, including 18 with GPi implants and 18 with STN implants. They then looked at how DBS changed activity across different brain networks and whether those changes were linked to improvements in symptoms and other clinical outcomes. 

The scans showed that DBS affects much more than the small area where the electrodes are placed. 

“Our work suggests the powerful effects of DBS are the result of widespread changes rather than only at the site where the electrodes are implanted and stimulation is applied,” says Dr. Brendan Santyr, the study’s first author. 

In both groups of patients, DBS influenced activity in a network of brain regions involved in planning and controlling movement. Increased activity in this movement network was associated with improvements in motor symptoms, regardless of which brain target was stimulated. 

However, the researchers also found important differences between the two targets. While both GPi and STN stimulation improved movement symptoms, they appeared to affect specific symptoms in different ways. The team also found that changes in activity within the movement network were linked to differences in language functioning among patients receiving GPi stimulation. This relationship was not seen in patients receiving STN stimulation. 

Together, the findings add to growing evidence that DBS works by influencing networks of connected brain regions rather than individual brain structures alone. Although larger studies are needed to confirm these results, this work represents an important step toward better tailoring DBS treatments to individual patients, helping maximize benefits while minimizing side effects. 

Dr. Brendan Santyr, a Neurosurgery Resident at the Schulich School of Medicine and former PhD candidate at the University of Toronto, is the first author of this study. 

Dr. Andres Lozano, Senior Scientist at UHN’s Krembil Brain Institute (KBI), and Dr. Alfonso Fasano, Clinician Investigator at KBI and an Affiliate Scientist at UHN’s KITE Research Institute, are co-senior authors of this study. They are also Professors at the University of Toronto Temerty Faculty of Medicine.

This work was supported by the Michael J. Fox Foundation, Parkinson Canada, the European Joint Program Neurodegenerative Disease Research, the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, and UHN Foundation.  

Dr. Lozano is the scientific director of Functional Neuromodulation Ltd. and a consultant for Medtronic, Abbott, Boston Scientific, and Insightec, as well as shares intellectual property related to this manuscript. Dr. Fasano received honoraria and/or research support from Abbott, AbbVie, Boston Scientific, Ceregate, Inbrain, and Medtronic for research outside of that described herein. For a full list of competing interests, see the manuscript. 

Santyr B, Chow C, Germann J, Boutet A, Ajala A, Qiu J, Loh A, Alhashyan I, Abbass M, Elias G, Sarica C, Vetkas A, Yang A, Yeo D, Kalia S, Cohn M, Fasano A, Lozano AM. fMRI during active GPi DBS uncovers target-specific networks. NPJ Parkinsons Dis. 2026 Jul 14. doi: 10.1038/s41531-026-01476-8. Epub ahead of print.