Objective: To evaluate changes in force-tracking (FT) fMRI activation patterns and motor performance over time using initial deep brain stimulation (DBS) settings optimized after three months post-surgery (Visit 1) and reassess these parameters at Visit 2 (six months later) under DBS-ON and DBS-OFF conditions.

Background: DBS of the subthalamic nucleus (STN) is a well-established treatment for Parkinson’s disease (PD) (1). Typically, DBS programming is adjusted iteratively to optimize therapeutic benefits (2). In this study, initial optimal DBS settings were maintained unchanged for the follow-up visit to determine how early fixed DBS settings impact motor function and brain activation over time.

Method: Four STN-DBS patients (all males, aged 65 ± 4.56 years) underwent functional MRI (fMRI) during a sinusoidal FT task (3, 4) at two visits: Visit 1 and Visit 2. Although patients underwent clinical DBS re-optimization after Visit 1, the study continued using their Visit 1 settings for comparison. Task-related T-values were extracted from key motor regions using SPM, motor function was assessed using the MDS-UPDRS-III, and FT accuracy was evaluated using root mean square error (RMSE). Wilcoxon signed-rank tests were conducted to compare DBS-ON vs. DBS-OFF effects at each visit.

Results: DBS-ON improved MDS-UPDRS-III scores at both visits compared to DBS-OFF, with greater improvement at Visit 1 (Fig1). DBS-ON improved FT accuracy at Visit 1, as indicated by lower RMSE values, but this advantage diminished at Visit 2 (Fig2). At Visit 1, DBS-ON increased activation in motor regions compared to DBS-OFF (Fig3). At Visit 2, DBS-OFF activation increased compared to Visit 1, while DBS-ON activation decreased in several regions (Fig4). Differences between DBS-ON and DBS-OFF were not statistically significant at either visit, likely due to small sample size or individual variability.

Conclusion: Over six months, patients’ response to initial optimized DBS settings declined, with higher UPDRS-III scores, reduced FT accuracy, and reversed fMRI activation patterns at Visit 2, suggesting a possible homeostatic equilibrium where neural adaptations alter stimulation effects over time. Although the study maintained the same DBS settings, routine clinical evaluations resulted in an average increase of 12.84% in display amplitude on the left side and a decrease of 14.50% on the right side.

Motor Performance Under DBS-ON vs. OFF at 2 Visits

RMSE Under DBS-ON vs. OFF at 2 Visits

T-values at Visit 1: DBS-ON vs. OFF

T-values at Visit 2: DBS-ON vs. OFF

References: 1. McIntyre CC, Savasta M, Walter BL, Vitek JL. How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophysiol. 2004;21(1):40-50.
2. Wagle Shukla A, Zeilman P, Fernandez H, Bajwa JA, Mehanna R. DBS Programming: An Evolving Approach for Patients with Parkinson’s Disease. Parkinsons Dis. 2017;2017:8492619.
3. Vijayakumari A, Piccinin C, Alberts J, Bhattacharya P, Lowe M, Walter B. STN-DBS Frequency Effects in Parkinson’s: An fMRI Study. Mov Disord2024.
4. Alberts JL, Phillips M, Lowe MJ, Frankemolle A, Thota A, Beall EB, et al. Cortical and motor responses to acute forced exercise in Parkinson’s disease. Parkinsonism & Related Disorders. 2016;24:56-62.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-effects-of-initial-deep-brain-stimulation-settings-on-force-tracking-brain-activation-and-motor-performance-in-parkinsons-disease/