Abstract
Background
Image-guided programming (IGP) enables optimization and personalization of deep brain stimulation (DBS) for patients with Parkinson's disease. Although its role in initial programming has been examined, evidence for its value in chronic stimulation remains limited. We aimed to evaluate the effectiveness of IGP in individuals with Parkinson's disease receiving chronic subthalamic nucleus (STN)-DBS with conventional programming (CP).
Methods
We reviewed optimal stimulation configurations using IGP with STIMVIEW™ XT in 30 patients with PD implanted with directional DB2202 electrodes. When discrepancies were identified between CP- and IGP-derived configurations, stimulation parameters were adjusted. Motor outcomes were assessed using the Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Parts III and IV and levodopa equivalent daily dose (LEDD) at baseline and 1 month after switching to IGP.
Results
Discrepancies between CP- and IGP-selected configurations were found in at least one electrode in 20 patients (66.7%), and 18 were included in the analysis. Of these, 11 (61.1%) showed improvement in MDS-UPDRS Part III and/or IV scores, 4 (22.2%) showed no change, and 3 (16.7%) worsened. Mean MDS-UPDRS Part III scores significantly decreased from 20.7 ± 16.5 to 16.9 ± 13.3 (p = 0.008), and LEDD from 655.2 ± 326.6 mg to 609.9 ± 311.1 mg (p = 0.046). Discrepancies occurred more often in stimulation direction than level, and IGP-based stimulation was applied bilaterally in most individuals.
Conclusion
IGP for STN-DBS can improve motor symptom control in patients with Parkinson's disease. It may benefit those with suboptimal outcomes under CP and represent a practical approach for individualized DBS management.
Keywords: Parkinson's disease, deep brain stimulation, subthalamic nucleus, image-guided programming, personalized stimulation
Plain language summary
Using Brain Imaging to Fine-Tune Deep Brain Stimulation in Parkinson's Disease: How Image-Guided Programming May Improve Long-Term Outcomes Compared to Conventional Programming
Deep brain stimulation (DBS) is a treatment for people with advanced Parkinson's disease. It works by sending small electrical signals to a part of the brain called the subthalamic nucleus (STN). DBS can help reduce movement problems, but finding the best settings for each patient is often difficult. Traditionally, doctors use a step-by-step approach called conventional programming (CP). This method tests each electrode contact and adjusts settings based on immediate changes in symptoms. While effective, CP can be time-consuming and sometimes fails to identify the most helpful stimulation points, especially when patients have complex or fluctuating symptoms.
Image-guided programming (IGP) is a newer approach that uses brain scans and computer software to show the exact position of the DBS electrodes. This allows doctors to see which contacts are closest to the areas most likely to improve movement, while avoiding regions that may cause side effects. In our study, we tested IGP in patients who had already been receiving DBS for several years. We compared their outcomes after switching from CP to IGP.
We found that more than half of the patients improved with IGP, showing better movement scores and needing slightly less medication. The improvements were most noticeable in patients who had more motor complications, such as involuntary movements or fluctuations in their symptoms. Importantly, IGP did not cause new side effects and was safe to use.
These results suggest that IGP is not only useful when DBS is first started but can also help patients who are already on long-term treatment. By providing doctors with clear visual guidance, IGP may make DBS programming more efficient and more effective. This approach could help many people with Parkinson's disease achieve better control of their symptoms and improve their quality of life.
Introduction
Subthalamic nucleus-deep brain stimulation (STN-DBS) is an established therapeutic approach for patients with advanced Parkinson's disease.1,2 Multiple factors, including careful patient selection, accurate electrode placement within the target structure, and appropriate stimulation parameters, are critical for achieving optimal outcomes. Recently, there has been growing interest in individualized programming to maximize therapeutic efficacy while minimizing stimulation-related adverse effects. Even with precise lead placement in the STN, comprehensive evaluation of all available contacts remains essential for determining the most effective stimulation configuration. However, the small size of functional subregions and their proximity to neighboring structures that may induce unwanted effects can reduce the overall efficacy of DBS.3,4
Conventional programming (CP) with monopolar review remains the standard approach for initial programming. CP involves monitoring clinical changes in parkinsonian symptoms and side effects while adjusting each electrode contact. This process demands considerable time and effort from both patients and clinicians, and its complexity has increased with the introduction of directional leads that offer additional contacts.5–7 Because CP relies on immediate symptom responses, predicting long-term efficacy or adverse effects can be difficult, particularly when changes are subtle and not readily perceived by patients during programming. Furthermore, some stimulation-induced effects can resemble parkinsonian features, complicating interpretation. 8
Image-guided programming (IGP) integrates patient-specific three-dimensional reconstruction of brain structures, visualization of lead trajectories, and anatomical mapping of contact locations, thereby facilitating more efficient DBS adjustment. 9 Recent reports suggest that IGP achieves clinical outcomes comparable to CP while reducing programming time in patients with Parkinson's disease.10–12 On the basis of these findings, IGP has become well-recognized for initial programming, offering clinicians visual guidance for targeting optimal stimulation zones. However, its utility in troubleshooting or managing chronic stimulation remains underexplored. Therefore, this study investigated the effectiveness of IGP in patients with Parkinson's disease undergoing chronic STN-DBS. We aimed to determine whether IGP improves motor outcomes in patients undergoing chronic STN-DBS compared to CP, and to address the underexplored role of IGP in long-term management.
Methods
Study design and participants
In this prospective study, we screened patients with Parkinson's disease who had undergone bilateral STN-DBS with directional electrodes (Vercise Cartesia DB2202; Boston Scientific, Marlborough, MA, USA) at Samsung Medical Center between 2019 and 2023. STN-DBS was performed as described previously. 13 We included patients with Parkinson's disease who had received chronic subthalamic stimulation for at least 6 months after initial programming, were on stable medication for at least 3 months, and had regular clinical follow-up. The study design is illustrated in Figure 1.
Figure 1.
Flowchart of patient selection and assessments comparing CP and IGP in STN-DBS. Abbreviations: CP, Clinical programming; IGP, Image-guided programming; STN-DBS, Subthalamic nucleus-Deep brain stimulation; LEDD, Levodopa equivalent daily dose; MDS-UPDRS, Movement Disorder Society-Unified Parkinsons's Disease Rating Scale.
Two neurologists (JSL and JH), blinded to patient outcomes and the existing stimulation parameters, independently identified the optimal stimulation configuration. Concordance was defined as complete agreement between the clinically active CP configuration and the consensus IGP configuration with respect to the active contact level and directional segment. Any difference in either parameter was classified as a mismatch. Of the 30 included patients with STN-DBS, 20 (66.7%) showed a mismatch between the stimulation configurations selected by CP and IGP in at least one electrode. These 20 patients were subsequently enrolled and received stimulation using IGP-selected configurations. Clinical data, including levodopa equivalent daily dose (LEDD), the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and IV scores, and MDS-UPDRS Part III score in the ON-medication and ON-stimulation state, were evaluated at baseline and 1 month after switching to IGP-based stimulation.
Clinical outcomes of IGP-based stimulation were classified according to previously established minimum clinically important difference thresholds for MDS-UPDRS Parts III and IV: “Better” if Part III improved by ≥3 points or Part IV improved by ≥1 point compared with CP-based stimulation; “Worse” if Part III worsened by ≥5 points or Part IV worsened by ≥1 point; and “Neutral” if changes did not meet these thresholds or if results between Parts III and IV were inconsistent. 11 Patients showing improvement with IGP were defined as “responders,” and those with neutral or worse outcomes as “non-responders” for comparison.
Conventional programming
A comprehensive monopolar review was conducted 1 month after DBS surgery by an experienced DBS specialist (JY). Each of the four contact levels was first tested using circular stimulation, followed by assessment of all directional segments to determine thresholds for clinical benefit and adverse effects. Test stimulation was delivered with a pulse width of 60 µs and a frequency of 130 Hz, with amplitude increased in 0.5 mA increments. After evaluating all levels and directional contacts, optimal contacts were selected as those providing maximal benefit or the widest therapeutic window. Before applying IGP, additional adjustments were made during regular follow-up for at least 6 months, and all participants maintained stable stimulation parameters for at least 3 months.
New stimulation based on image-guided programming
IGP was performed with STIMVIEW™ XT (Boston Scientific, Marlborough, MA, USA) by two neurologists (JSL and JH) who were blinded to patients’ stimulation parameters and clinical outcomes. Digital Imaging and Communications in Medicine imaging datasets were obtained from all patients, including preoperative three-dimensional sagittal T2-weighted MRI, three-dimensional axial T1-weighted MRI acquired on a Philips Achieva 3.0-T scanner (Best, The Netherlands), and postoperative three-dimensional helical stereotactic CT. These sequences were imported into the software and automatically co-registered using image-fusion algorithms to visualize patient-specific brain anatomy. The software then detected the leads and determined their orientation based on postoperative CT.
Blinded investigators identified the orientation of the bilateral leads using three-dimensional reconstruction. The dorsolateral portion of the STN was then identified on patient-specific anatomical models in STIMVIEW™ XT (Figure 2). Because no universally accepted anatomical boundary for the dorsolateral STN is established, target delineation was based on the patient-specific anatomical representation available in STIMVIEW™ XT and the investigators’ anatomical assessment. On each side, a novel IGP-based configuration was created to maximize coverage of the visually delineated dorsolateral STN while minimizing spread to surrounding structures, such as the substantia nigra and internal capsule, with both stimulation direction and level considered. In cases of disagreement regarding the optimal contact, the neurologists discussed their findings and reached consensus. Once the target was determined, the amplitude was set to 0.5 mA below the adverse-effect threshold identified through IGP. Other parameters, including pulse width and frequency, remained unchanged from CP. The new stimulation parameters, including contact level or direction, were applied unilaterally or bilaterally depending on the mismatched side(s).
Figure 2.
Three-dimensional schematic illustration of the subthalamic nucleus. Note: The STN is shown in blue, the VTA in red, and the DBS lead in gray. The left STN is shown as a representative example. The dorsolateral portion of the STN is delineated by a white dotted contour in panels A and C. Panel A shows a view emphasizing the lateral aspect of the STN, whereas panel B shows a view emphasizing its medial aspect. Panel C provides a superior (top-down) view, in which the DBS lead appears as a white circular cross-section. Abbreviations: DBS, deep brain stimulation; VTA, volume of tissue activated; dlSTN, dorsolateral portion of the subthalamic nucleus.
Patients were monitored for at least 1 h for potential adverse effects after switching to IGP. Clinical outcomes were assessed at baseline under CP and at 1 month after implementation of the IGP-based program. At the 1-month follow-up visit, dopaminergic medications were adjusted by the DBS specialist based on routine clinical assessment of overall symptom control, including motor fluctuations, dyskinesia, and stimulation-related adverse effects. At 3 months after implementation of IGP, the stimulation program status of patients who showed clinical improvement at 1 month was reviewed to determine whether they continued to use the IGP-based stimulation settings or had reverted to their previous conventional settings.
Statistical analyses
Data normality was assessed using the Kolmogorov–Smirnov test. Continuous variables are expressed as mean ± standard deviation. Paired t-tests or Wilcoxon signed-rank tests were used to compare clinical outcomes between CP- and IGP-based stimulation within the same patients. Group comparisons between responders and non-responders were performed using independent t-tests or Mann–Whitney U tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. All statistical tests were two-tailed, and significance was set at p < 0.05. Analyses were conducted using SPSS version 29.0 (IBM Inc., USA) for Windows.
Results
Participants and clinical variables
Among the 20 patients with Parkinson's disease undergoing STN-DBS, 18 (13 male and 5 female) agreed to undergo new stimulation based on IGP, whereas 2 declined stimulation modification. The mean age, disease duration at baseline, and duration from DBS surgery to baseline evaluation were 60.1 ± 8.3 years, 13.6 ± 5.3 years, and 2.6 ± 1.5 years, respectively. Demographic and clinical characteristics are summarized in Table 1.
Table 1.
Demographics and clinical characteristics of patients undergoing STN-DBS.
| ID | Sex | Age (y) | Disease duration (y) | LEDD (mg) | MDS-UPDRS III | MDS-UPDRS IV | Clinical outcome | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Pre | Post | Pre | Post | Pre | post | |||||
| 1 | F | 70 | 16.8 | 1310 | 1100 | 25 | 17 | 5 | 3 | Better |
| 2 | F | 52 | 15.8 | 985 | 985 | 6 | 6 | 4 | 2 | Better |
| 3 | M | 47 | 12.8 | 495 | 495 | 8 | 9 | 2 | 0 | Better |
| 4 | F | 46 | 13.8 | 555 | 555 | 21 | 21 | 0 | 3 | Worse |
| 5 | M | 68 | 11.8 | 225 | 225 | 13 | 16 | 0 | 0 | Neutral |
| 6 | F | 66 | 23.8 | 900 | 975 | 17 | 18 | 3 | 5 | Worse |
| 7 | M | 44 | 13.2 | 725 | 625 | 22 | 20 | 2 | 2 | Neutral |
| 8 | M | 65 | 11.4 | 1075 | 925 | 43 | 38 | 4 | 2 | Better |
| 9 | M | 63 | 26.8 | 300 | 300 | 72 | 57 | 0 | 0 | Better |
| 10 | M | 68 | 15.8 | 1064 | 1064 | 19 | 7 | 2 | 0 | Better |
| 11 | M | 61 | 9.7 | 700 | 700 | 15 | 7 | 3 | 0 | Better |
| 12 | M | 62 | 9.8 | 300 | 300 | 40 | 27 | 1 | 0 | Better |
| 13 | M | 64 | 9.4 | 375 | 375 | 9 | 8 | 0 | 0 | Neutral |
| 14 | F | 52 | 14.4 | 600 | 300 | 9 | 8 | 8 | 3 | Better |
| 15 | M | 61 | 15.3 | 187.5 | 187.5 | 19 | 19 | 0 | 2 | Worse |
| 16 | F | 60 | 10.9 | 912.5 | 912.5 | 10 | 9 | 4 | 4 | Neutral |
| 17 | M | 70 | 10.4 | 559 | 429 | 20 | 16 | 3 | 3 | Better |
| 18 | M | 62 | 3.4 | 525 | 525 | 5 | 2 | 5 | 1 | Better |
| Mean | 60.1 | 13.6 | 655.2 | 609.9 | 20.7 | 16.9 | 2.6 | 1.7 | ||
| SD | 8.3 | 5.3 | 326.6 | 311.1 | 16.5 | 13.3 | 2.2 | 1.6 | ||
| p-value | 0.046 | 0.008 | 0.088 | |||||||
STN-DBS, Subthalamic nucleus-Deep brain stimulation; LEDD, Levodopa equivalent daily dose; MDS-UPDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale; SD, Standard deviation.
Bold values denote statistical significance (p < 0.05).
Clinical outcomes after applying image-guided programming
Of the 18 patients, IGP-based stimulation was applied bilaterally in 15 (83.3%) and unilaterally in 3 (16.7%). Comparing the best stimulation contacts between CP and IGP across 36 electrodes revealed discrepancies in level in 22 electrodes (61.1%) and in direction in 30 electrodes (83.3%). Discrepancies in both direction and level occurred in 17 electrodes (47.2%), whereas the same best contacts were identified by both CP and IGP in 3 electrodes (8.3%). Overall, direction changes outnumbered level changes on both sides (right: 78% vs 56%; left: 83% vs 61%). Detailed targets for baseline and new stimulation are presented in Table 2.
Table 2.
Detailed lead contacts between CP and IGP in patients undergoing STN-DBS.
| ID | CP (right) † | IGP (right) † | Changes | CP (left) † | IGP (left) † | Changes |
|---|---|---|---|---|---|---|
| 1 | 2A (100), 3.6 | 1 (20) 2B/2C (60/20), 3.6 | Level/Direction | 2B/2C (75/25), 4.0 | 3C (100), 3.5 | Level/Direction |
| 2 | 2A/2B (50/50), 3.9 | 3A/3C (75/25), 3.4 | Level/Direction | 2A/2C (60/40), 3.6 | 3A/3B (75/25), 3.6 | Level/Direction |
| 3 | 3A/3C (50/50), 6.1 | 1 (20) 2B/2C (40/40), 6.1 | Level/Direction | 3B/3C (50/50), 4.0 | 2B/2C (20/60) 3B/3C (5/15), 3.5 | Level/Direction |
| 4 | 4 (100), 3.5 | 4 (100), 3.5 | None | 4 (100), 4.1 | 3A/3B/3C (17/17/16) 4 (50), 4.1 | Level/Direction |
| 5 | 2A/2B/2C (34/33/33), 2.9 | 2B (100), 2.9 | Direction | 2A/2B/2C (34/33/33), 5.0 | 2A/2B (20/20) 3A/3B (30/30), 5.0 | Level/Direction |
| 6 | 3A/3B/3C (7/7/6) 4 (80), 4.6 | 3A/3B (8/22) 4 (70), 4.5 | Level/Direction | 2A/2B/2C (34/33/33), 2.7 | 2A/2B/2C (34/33/33), 2.7 | None |
| 7 | 3A (100), 5.5 | 3A/3C (52/18) 4 (30), 5.5 | Level/Direction | 3A (100), 3.6 | 3A/3B (75/25), 3.5 | Direction |
| 8 | 3A (100), 3.2 | 3A/3C (25/75), 3.2 | Direction | 3A (100), 3.9 | 3B (100), 3.9 | Direction |
| 9 | 3A/3B/3C (34/33/33), 4.5 | 3A/3C (75/25), 4.5 | Direction | 3A/3B/3C (34/33/33), 4.2 | 3A/3B (40/40) 4 (20), 4.0 | Direction |
| 10 | 3A/3B/3C (34/33/33), 4.0 | 2B/2C (22/8) 3B/3C (52/18), 4.0 | Level/Direction | 3A/3B/3C (34/33/33), 4.5 | 2B (30) 3B (70), 4.5 | Level/Direction |
| 11 | 2A/2B (50/50) 3A/3B (50/50), 2.6 | 2B (50) 3B (50), 2.8 | Direction | 2B/2C (50/50) 3B/3C (50/50), 4.3 | 2C (50) 3C (50), 4.3 | Direction |
| 12 | 2A/2B/2C (17/17/16) 3A/3B/3C (17/17/16), 6.0 | 2B (60) 3B (40), 5.5 | Level/Direction | 3A/3B/3C (34/33/33), 3.5 | 2C (30) 3C (70), 4.0 | Level/Direction |
| 13 | 2A/2B/2C (34/33/33), 5.0 | 2B/2C (75/25), 5.0 | Direction | 3A/3B/3C (34/33/33), 4.5 | 3B/3C (25/75), 4.5 | Direction |
| 14 | 2A/2C (75/25), 4.5 | 2A/2C (38/12) 3A/3C (38/12), 5.0 | Level | 3A/3B (75/25), 4.1 | 3A/3B (75/25), 3.6 | None |
| 15 | 3A/3C (50/50), 3.0 | 3A/3C (25/25) 4 (50), 3.5 | Level | 3B (100), 1.8 | 3B (50) 4 (50), 2.3 | Level |
| 16 | 4 (100), 4.3 | 3A/3C (30/10) 8 (60), 4.3 | Level/Direction | 3A/3C (75/25), 4.8 | 3A/3B (45/15) 4 (40), 4.8 | Level/Direction |
| 17 | 2B/2C (50/50) 3B/3C (50/50), 3.5 | 3B/3C (20/20) 4 (60), 3.5 | Level/Direction | 2B (40) 3B (60), 3.3 | 3B/3C (25/75), 2.8 | Level/Direction |
| 18 | 3C (100), 1.0 | 3A/3C (25/75), 1.5 | Direction | 3A/3B/3C (34/33/33), 3.0 | 2A/2B (75/25), 2.5 | Level/Direction |
CP, Clinical programming; IGP, Image-guided programming; STN-DBS, Subthalamic Nucleus-Deep brain stimulation.
† The lead contacts are numbered from 1 (most ventral) to 8 (most dorsal). Contacts 2A-2C and 3A-3C correspond to the directional segments at the second and third levels, respectively. The percentage of the total stimulation delivered through each active contact is indicated in parentheses, followed by the corresponding stimulation amplitude in mA.
Application of IGP-based stimulation resulted in a significant reduction in MDS-UPDRS Part III and/or IV scores in 11 patients (“Better,” 61.1%), equivocal changes in 4 (“Neutral,” 22.2%), and worsening in 3 (“Worse,” 16.7%). No patient experienced significant adverse effects during the 1-h observation period after switching to IGP or throughout the 1-month follow-up, except one “Worse” patient who developed severe dyskinesia during follow-up. MDS-UPDRS Part III scores significantly decreased by 18.4%, from 20.7 ± 16.5 to 16.9 ± 13.3 (p = 0.008), whereas changes in Part IV scores were not statistically significant. LEDD decreased by 6.9%, from 655.2 ± 326.6 mg to 609.9 ± 311.1 mg (p = 0.046) (Table 1). Of the 11 patients who showed clinical improvement at 1 month, 10 (90.9%) elected to continue using the IGP-based stimulation settings, whereas 1 (9.1%) reverted to their previous conventional settings. Representative pre- and post-IGP STIMVIEW™ XT images from a patient with an improved outcome and a patient with a worsened outcome are shown in Figure 3.
Figure 3.
Representative cases with favorable and unfavorable clinical outcomes following IGP. Note: (A, B) Favorable outcome (“Better”; patient 8). The left STN is shown before (A) and after (B) IGP. In the initial program (A), stimulation was delivered through contact 3A (100%). After IGP (B), the current was reassigned to contact 3B (100%), resulting in improved VTA coverage of the dorsolateral STN. (C, D) Unfavorable outcome (“Worse”; patient 15). The left STN is shown before (C) and after (D) IGP. In the initial program (C), stimulation was delivered through contact 3B (100%). After IGP (D), the current was redistributed between contacts 3B and 4 (50% each). Although this adjustment increased the overall VTA–STN overlap, the additional VTA coverage was predominantly located in the anterior STN rather than the intended dorsolateral subregion. For each case, posterior views are shown above and superior views below, with the corresponding directional contact configurations displayed to the left of each panel. The STN is shown in blue, the VTA in red, and the DBS lead in gray. In the superior views, the lead is shown in cross-section. Abbreviations: Lt, left; Rt, right; S, superior; I, inferior; Ant, anterior; Pos, posterior; IGP, image-guided programming; STN, subthalamic nucleus; VTA, volume of tissue activated; DBS, deep brain stimulation.
Comparison of demographics and programming discrepancies by clinical outcome
When dividing patients into responders (n = 11) and non-responders (n = 7) based on clinical response to IGP, baseline demographics, including age, sex, disease duration, and LEDD, were comparable between groups (Table 3). Baseline motor severity, assessed by MDS-UPDRS Part III, also did not differ significantly. In contrast, baseline MDS-UPDRS Part IV scores were significantly higher in responders than in non-responders (3.4 ± 2.2 vs. 1.3 ± 1.7; p = 0.04). Bilateral IGP application was more frequent among responders than non-responders (90.9% vs. 71.4%), although this difference was not statistically significant.
Table 3.
Comparison of baseline characteristics and IGP features between outcome groups.
| Responders (n = 11) | Non-responders (n = 7) | p-value | |
|---|---|---|---|
| Age, years | 61.1 ± 7.7 | 58.4 ± 9.6 | 0.54 |
| Sex, male (%) | 8 (72.7) | 4 (57.1) | 0.63 |
| Disease duration, years | 13.4 ± 5.9 | 14.0 ± 4.7 | 0.82 |
| MDS-UPDRS III (pre) | 23.8 ± 20.5 | 15.9 ± 5.2 | 0.25 |
| MDS-UPDRS IV (pre) | 3.4 ± 2.2 | 1.3 ± 1.7 | 0.04 |
| LEDD (pre), mg | 719.4 ± 338.4 | 554.3 ± 303.3 | 0.30 |
| Bilateral IGP application, n (%) | 10 (90.9) | 5 (71.4) | 0.53 |
| Electrode discrepancies | |||
| Level only, n (%) | 1 (9.1) | 1 (14.3) | 1.00 |
| Direction only, n (%) | 3 (27.3) | 1 (14.3) | 1.00 |
| Level and direction, n (%) | 7 (63.6) | 5 (71.4) | 1.00 |
IGP, Image-guided programming; MDS-UPDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale; LEDD, Levodopa equivalent daily dose.
Bold values denote statistical significance (p < 0.05).
Regarding electrode discrepancies, both groups showed a similar distribution. In responders, most discrepancies involved combined level and direction changes (63.6%), followed by direction only (27.3%) and level only (9.1%). Non-responders exhibited a comparable pattern, with the majority involving both level and direction (71.4%), and fewer involving direction only (14.3%) or level only (14.3%). None of these distributions differed significantly between groups.
Discussion
This study evaluated the use of IGP in patients with Parkinson's disease undergoing chronic STN-DBS with CP. Previous studies have shown that IGP improves programming efficiency in STN-DBS.10–12,14–19 Most prior investigations focused on initial programming and reported outcomes comparable to CP but with reduced programming time and fewer stimulation-related adverse effects.10,14–16 In contrast, we applied IGP in patients undergoing chronic stimulation and assessed clinical changes 1 month after the new programming. We also evaluated motor symptoms (MDS-UPDRS Part III), motor complications (MDS-UPDRS Part IV), and medication dose (LEDD). Thus, our study may better reflect real-world clinical practice than earlier reports.
Among factors contributing to dissatisfaction with chronic STN-DBS treatment, suboptimal stimulation settings remain a key concern. 20 The effectiveness of CP, which depends largely on clinical judgment, can be influenced by the clinician's experience, available time, and quality of patient feedback. Moreover, long-term stimulation effects or side effects may present acutely after parameter adjustments, and stimulation-induced phenomena can resemble parkinsonian symptoms. 8 Although all patients were maintained on stable stimulation and medication regimens, IGP yielded additional clinical benefit. In our analysis, most discrepancies between CP and IGP involved stimulation direction (83.3%), followed by level (61.1%). Notably, responders to IGP exhibited higher baseline motor complications, such as fluctuation and dyskinesia (higher MDS-UPDRS Part IV scores), suggesting that patients with fluctuating motor states or suboptimal control under CP may benefit most from IGP. Together, these findings indicate that IGP serves as a valuable troubleshooting tool for optimizing chronic STN-DBS management.
Our study confirmed that more than half of the patients (61.1%) who underwent IGP showed improved clinical outcomes, as evidenced by meaningful reductions in MDS-UPDRS Part III or IV scores and decreased medication doses. In most cases, adjustments were required in both direction and level, with directional changes occurring more frequently on both sides. Although not statistically significant, bilateral adjustments in both direction and level were more common among responders (10/11, 90.9%) than among non-responders (5/7, 71.4%), showing a numerical trend toward greater improvement in patients who underwent more extensive reconfiguration. These results indicate that clinical benefits can be achieved by optimizing the stimulation site alone, without modifying pulse width or frequency.
To achieve optimal outcomes, it is essential to individualize stimulation parameters and ensure precise electrode positioning within the STN.11,21 In clinical practice, however, the advent of directional leads has increased programming complexity, requiring additional time and expertise. In this context, user-friendly IGP represents a valuable approach that enables clinicians to adjust DBS settings more efficiently. Previous evidence has shown that electrical stimulation within the dorsolateral STN, the region widely regarded as the “sweet spot”, produces the greatest motor benefit, although some disagreement persists among DBS specialists regarding the optimal STN subregion.4,21–24 In our study, stimulation targeting the dorsolateral portion resulted in an average 18.4% reduction in MDS-UPDRS Part III scores. Unlike most prior reports focusing on initial programming, our study applied IGP in patients on chronic stimulation and demonstrated that meaningful improvement could still be achieved. These findings suggest that IGP is not only a tool for programming efficiency but also a valuable strategy for re-optimizing patients who appear clinically stable yet remain suboptimally managed. Thus, IGP may help refine long-term DBS management and expand therapeutic potential in everyday clinical practice.
In most cases with improvement from IGP, directional current steering enhanced bilateral VTA coverage of the dorsolateral STN, potentially increasing engagement of the sensorimotor territory and correcting a chronically suboptimal stimulation configuration (Figure 3A–B). In contrast, in patients with worse responses to IGP, the additional coverage was predominantly located outside the intended dorsolateral portion, potentially resulting in less effective engagement of the optimal motor territory (Figure 3C–D). Together, these observations suggest that the spatial distribution of VTA coverage within the STN, particularly its correspondence with the dorsolateral subregion, may be more relevant to clinical outcome than the overall degree of anatomical overlap. Thus, increased anatomical overlap alone may not reliably translate into clinical benefit. However, Patient 4 developed refractory stimulation-induced dyskinesia despite improved VTA coverage of the dorsolateral STN following IGP. Therefore, IGP does not eliminate the need for clinical judgement, even when image-based optimization suggests improved anatomical targeting. To address this limitation, advanced imaging approaches, such as connectivity-based analysis integrated with conventional structural imaging, may allow functional mapping tailored to each patient and support the development of fully personalized stimulation parameters.
This study has several limitations. First, the study was neither blinded nor randomized, and therefore the potential influence of placebo or expectation effects cannot be excluded. Although significant improvements in MDS-UPDRS Part III scores were observed following IGP, these findings should be interpreted with appropriate caution. However, the stimulation parameters from IGP were determined by blinded movement disorders specialists (JH and JSL), and blinded or randomized study designs can be challenging in patients with chronic stimulation, especially when they are relatively satisfied with baseline DBS parameters. Despite these limitations, our findings may have clinical relevance for routine practice by suggesting that IGP could provide an additional approach for re-optimizing stimulation in patients receiving chronic DBS. Future randomized or blinded controlled studies are needed to confirm the observed clinical benefit. Second, the follow-up period was limited to 1 month, precluding assessment of the long-term durability of the observed clinical improvements and medication changes. To partially address this limitation, we reviewed the stimulation program status at the 3-month follow-up. Notably, most patients (10/11, 90.9%) who had shown improvement following IGP continued to use the IGP-based stimulation settings. Prospective studies with longer follow-up periods are needed to determine whether the benefits of IGP are sustained over time. Third, the study was conducted at a single center with a relatively small and highly selected cohort, which may limit the generalizability of our findings. Nevertheless, clinically meaningful improvements were observed despite the limited sample size. Lastly, parameters such as pulse width and frequency were held constant to minimize confounding factors. However, optimization of stimulation location alone may not fully capture the therapeutic potential of DBS. Larger, multicenter prospective studies are warranted to validate our findings and evaluate the effects of optimizing multiple stimulation parameters simultaneously.
In conclusion, we demonstrated the benefits of IGP in patients with Parkinson's disease undergoing chronic STN-DBS. Specifically, IGP may offer meaningful improvement in patients who show suboptimal outcomes with CP and can yield additional benefits even in those maintained on chronic stimulation. These findings support IGP as a promising approach for individualized, long-term DBS management.
Footnotes
ORCID iDs: Jun Seok Lee https://orcid.org/0009-0003-7877-8760
Jongmok Ha https://orcid.org/0000-0003-4886-7650
Sumin Kim https://orcid.org/0000-0002-8523-883X
Jin Whan Cho https://orcid.org/0000-0002-9145-6729
Jung-Il Lee https://orcid.org/0000-0001-8143-5513
Jinyoung Youn https://orcid.org/0000-0003-3350-5032
Ethical considerations: All the methods and experiments were designed and performed in accordance with the Declaration of Helsinki and relevant guidelines and regulations provided by the policies of Elsevier. This research was reviewed and approved by the Institutional Review Board of Samsung Medical Center (Approval No. SMC 2023-06-054).
Consent to participate: All enrolled participants provided written informed consent.
Consent for publication: Not applicable.
Author contributions: JSL contributed to conceptualization, data curation, formal analysis, investigation, software, writing – original draft preparation. JH contributed to conceptualization, data curation, formal analysis, investigation, and software. SK contributed to data curation, formal analysis, investigation, and software. JWC contributed to conceptualization, data curation, methodology, supervision, and validation. JIL contributed to conceptualization, data curation, methodology, supervision, validation. JY contributed to conceptualization, data curation, formal analysis, investigation, methodology, software, supervision, validation, and writing – review and editing. All authors have read and approved the final paper.
Funding: This research was supported by a grant of the Korea Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grand number: RS-2023-KH134527).
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
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