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. 2021 May 24;12:3043. doi: 10.1038/s41467-021-23311-9

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — BOLD response maps associated with left DBS-STN stimulation at multiple DBS lead A Contacts and B voltages for two a priori clinically optimized PD-STN patients. The fMRI BOLD signal changes at the optimal contact (A top row) and voltage (B middle row) are shown. Brain regions with a significant increase (hot colors, positive t-values, DBS-ON > OFF) and decrease (cool colors, negative t-value, DBS-ON < OFF) (p < 0.001, cluster size = 50) in BOLD response were identified. A The optimal contact showed changes in BOLD response in the left (ipsilateral) motor cortex and thalamus, and right (contralateral) cerebellum. We considered the clinically optimal contact as the origin (i.e., 0) and the non-optimal contacts were mapped as a function of distance in mm from the optimal contact. B When using the optimal stimulation contact, decreasing stimulation amplitude from optimal to low (subtherapeutic) voltage stimulation triggered a decrease in magnitude of the BOLD changes but maintained the topographic pattern. High (supratherapeutic) voltages produced a relatively stronger BOLD response in the left (ipsilateral) motor cortex and right (contralateral) cerebellum but was also accompanied by increased BOLD signal in non-motor regions such as the inferior frontal and occipital lobes. The subtherapeutic voltage was defined as 1.5 V below optimal voltage because a reduction of this magnitude yields a change in clinical status for most PD patients. The supratherapeutic voltage was defined as the voltage just below the side effects threshold (i.e., highest tolerated voltage). BOLD blood-oxygen-level-dependent, DBS deep brain stimulation, fMRI functional magnetic resonance imaging, PD Parkinson’s disease, STN subthalamic nucleus.