AIMS:Rheumatoid arthritis (RA) is associated with increased healthcare resource utilization and high-cost pharmacologic treatment. The objective of the current analysis was to evaluate the cost-effectiveness of vagus nerve-mediated neuroimmune modulation therapy (NIMT) using a novel implantable neurostimulation technology compared to status-quo pharmacologic treatment of moderate-to-severe rheumatoid arthritis patients in the US. MATERIALS AND METHODS:A decision-analytic Markov model was utilized to project strategy-specific costs and outcomes over 2-, 10-year, and lifetime horizons for NIMT and the status-quo. Clinical data from the RESET-RA study informed key model inputs including cohort characteristics, utilities, event rates, and medication utilization. Costs were derived from published literature and current reimbursement rates. The analysis was conducted from the US payer perspective, with both costs and outcomes discounted 3% in accordance with US cost-effectiveness guidelines. Cost-effectiveness was evaluated using established US willingness-to-pay thresholds of $50,000 (highly cost-effective) and $150,000 (cost-effective) per quality-adjusted life year (QALY) gained. Deterministic and probabilistic sensitivity analyses (PSA) were performed. RESULTS:Under the base case assumptions, NIMT was cost-saving in less than 2 years. Over lifetime, NIMT was associated with incremental cost-savings of $350,052 and QALY gain of 0.87, and led to cost-savings of $25,397 and $197,062, and concurrent incremental QALY gains of 0.10 and 0.46 at 2 and 10 years, rendering NIMT the dominant strategy across all three horizons. In the PSA, NIMT was cost-effective at thresholds of $50,000 and $150,000 per QALY gained in 96.25% and 99.20% of simulations at 2 years, and 100% of simulations at 10 years and lifetime. CONCLUSION:In this model-based analysis of a recent randomized trial, the use of NIMT therapy corresponded to a reduction in total costs of care, improved quality of life, and was found to be a highly cost-effective or dominant treatment option for moderate-to-severe rheumatoid arthritis in a US setting.

BACKGROUND Trigeminal neuropathic pain (TNP), particularly posttraumatic TNP (PTTN), is often refractory to medical therapy and difficult to manage surgically. Although radiofrequency thermoablation (RFA) of the gasserian ganglion is established, peripheral nerve RFA remains underutilized, particularly in anatomically complex cases. OBSERVATIONS A 62-year-old man developed severe left maxillary (V2) facial pain following sinus surgery, refractory to multiple pharmacological therapies and prior gasserian balloon rhizotomy. A diagnostic infraorbital nerve block produced significant temporary relief, supporting a peripheral pain generator and RFA consideration. An initial infraorbital nerve RFA performed with fluoroscopic guidance failed to provide durable benefit. A subsequent CT-guided infraorbital nerve RFA resulted in marked pain reduction. The patient later developed localized recurrent dysesthesia, prompting a third CT-guided, navigation-assisted RFA with sustained improvement. At the last follow-up (8, 6, and 3 months after the first, second, and third RFAs, respectively), his visual analog scale pain score improved from 10 to 2, with approximately 80% reduction in pain flares and significant quality of life improvement. LESSONS CT-guided infraorbital nerve RFA is a minimally invasive and effective option for refractory PTTN. Peripheral RFA, particularly when combined with advanced image guidance and potentially awake mapping, should be considered when central interventions fail or are contraindicated. https://thejns.org/doi/10.3171/CASE25553

Abstract Objectives Epidural spinal cord stimulation (SCS) is an emerging therapy for motor rehabilitation following spinal cord injury (SCI) and other motor disorders. Conventionally, SCS leads are placed along the dorsal spinal cord (SCS D ), where stimulation activates large diameter afferent fibers, which indirectly activate motoneurons through reflex pathways. This leads to broad activation of flexor and extensor muscles and limited fine-tuned control of motor output. Targeting the ventral spinal cord (SCS V ) may enable more direct activation of motoneuron pools, potentially improving the specificity of muscle activation; however, there is currently no established method to place leads ventrally. To address this, we evaluated the feasibility of four modified percutaneous implantation techniques to target the ventrolateral thoracolumbar spinal cord. Materials and methods Percutaneous SCS V implantation was performed in three human cadaver torso specimens under fluoroscopic guidance. The following approaches were evaluated: sacral hiatus, transforaminal, interlaminar contralateral, and interlaminar ipsilateral. The leads in the latter 3 approaches were inserted between L1 and L5. Eighteen implants were attempted, with nine leads retained for analysis. Lead and electrode position were assessed using computed tomography (CT) with three-dimensional reconstruction, along with anatomical dissection to verify lead and electrode placement within the epidural space. Results Successful ventral epidural lead placement was achieved using all four implantation approaches. The sacral hiatus (16/16 electrodes) and transforaminal (8/8 electrodes) approaches resulted in exclusively ventrolateral placement. The interlaminar contralateral approach led to 27/32 electrodes positioned ventrolaterally and 5/32 dorsally. The interlaminar ipsilateral implantation approach led to 14/32 electrodes positioned ventrolaterally and 18/32 positioned ventromedially. Conclusions These findings demonstrate that ventral epidural SCS lead placement can be achieved using modified percutaneous implant techniques. The four approaches outlined here provide a clinically feasible pathway to SCS V and establishes a foundation for future clinical studies investigating SCS V for motor rehabilitation following SCI.

OBJECTIVE:Essential tremor (ET) is a prevalent movement disorder that also includes nonmotor symptoms such as anxiety, depression, and cognitive impairment. Deep brain stimulation (DBS) is an established treatment for ET, yet its impact on nonmotor symptoms remains unclear. This study aims to describe neuropsychological outcomes following ventral intermediate nucleus (VIM) DBS in a large cohort of patients with ET and identify factors associated with changes in depression and cognitive function. METHODS:A retrospective cohort study of patients who had undergone VIM DBS was performed. Inclusion criteria were ET diagnosis, surgery between October 2007 and March 2020, and available pre- and post-DBS neuropsychological testing results. Neuropsychological measures included the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and cognitive measures assessing attention, executive function, language, memory, and visuospatial function. Post-DBS tremor improvement was graded, and active electrode coordinates and stimulation parameters were identified. Statistical analyses included descriptive statistics, t-tests to compare pre- and postoperative scores at the group level, and one-way analysis of variance to compare variables among patients who improved, were stable, or worsened in psychiatric and cognitive characteristics after DBS. RESULTS:One hundred thirty-nine patients met the study inclusion criteria. BDI-II scores significantly decreased postoperatively (9.82 ± 6.77 vs 8.29 ± 6.18, p < 0.001, Cohen's d = 0.176), whereas BAI scores remained unchanged. Both language (p = 0.003, Cohen's d = 0.259) and memory (p < 0.001, Cohen's d = 0.336) domains showed statistically significant small-magnitude declines following surgery, whereas attention, executive function, and visuospatial function were unchanged. Patients with improved depression (14.3%) following VIM DBS had significantly higher BDI-II scores preoperatively (p < 0.001, ω2 = 0.226). Patients with worsened language (18.7%) had higher preoperative language scores (p < 0.001, ω2 = 0.058). Patients with worsened memory (15.1%) had higher BAI scores preoperatively (p = 0.002, ω2 = 0.079). Preoperative scores were similar between patients with improved and worsened overall cognition postsurgery. Patients with improved overall cognition had improvements in attention, language, and visuospatial function. CONCLUSIONS:VIM DBS for ET did not result in large-magnitude neuropsychological changes. There were statistically significant, though likely not clinically meaningful, small-magnitude improvements in depression and worsening in language and memory scores. Associations were found between multiple preoperative mood and cognitive scores and post-DBS neuropsychological changes. These findings can help inform clinical decision-making and patient counseling for DBS.

High-bandwidth brain–computer interfaces rely on invasive surgical procedures or brain-penetrating electrodes. Here we describe a cortical 1,024-channel thin-film microelectrode array and we demonstrate its minimally invasive surgical delivery that avoids craniotomy in porcine models and cadavers. We show recording and stimulation from the same electrodes to large portions of the cortical surface, and the reversibility of delivering the implants to multiple functional regions of the brain without damaging the cortical surface. We evaluate the performance of the interface for high-density neural recording and visualizing cortical surface activity at spatial and temporal resolutions and total spatial extents. We demonstrate accurate neural decoding of somatosensory, visual and volitional walking activity, and achieve focal neuromodulation through cortical stimulation at sub-millimetre scales. We report the feasibility of intraoperative use of the device in a five-patient pilot clinical study with anaesthetized and awake neurosurgical patients, characterizing the spatial scales at which sensorimotor activity and speech are represented at the cortical surface. The presented neural interface demonstrates the highly scalable nature of micro-electrocorticography and its utility for next-generation brain–computer interfaces. A 1,024-channel microelectrode array is delivered to the brain cortex via a minimally invasive incision in the skull and dura, and allows recording, stimulation and neural decoding across large portions of the brain in porcine models and human neurosurgical patients.

BACKGROUND:Spinal cord stimulation (SCS) is a nonpharmacological, minimally invasive intervention designed to ameliorate chronic low back pain. However, meta-analyses have not supported the use of SCS due to a lack of high-quality evidence. This work provides the necessary information to design better statistically powered clinical trials for SCS by providing estimates and variances for various patient-reported outcomes and biometrics across time in this population. METHODS:A cohort of 18 patients was followed across 7 months before and after SCS implantation. The patients were administered a monthly battery of patient-reported outcomes, and daily biometrics were obtained. Multilevel Bayesian distributional models quantified the median and variance change across time, both of which are necessary in sample size calculations. Secondary to estimating effects, we also determine the probability of a directional effect and equivalence. RESULTS:Scales for pain show sustained improvements and stable variance. There were no changes in quality-of-life medians or variance. Robust improvements were made in fatigue and reported sleep quality, despite an unclear effect on total hours slept as recorded by the daily wearable. Resting heart rate decreased after SCS and had low changes in variance; whereas pulse rate variability/heart rate variability exhibited no median change across time but wild swings in variance, indicating it is a poor biomarker in this population. CONCLUSIONS:This study reports many patient-reported outcomes and digital biomarkers used in SCS clinical research, including which ones have potential value and the exact information necessary to plan future high-quality clinical trials in the SCS population. SIGNIFICANCE:There is currently only low-quality evidence that spinal cord stimulation is effective for low back pain. This study supplies all the necessary information (effect estimates, variances and within-measure correlations across time) to better estimate sample sizes, a primary criticism of current evidence in this population. We also provide a preliminary indication as to which patient-reported outcomes and wearable measures are most effective in a spinal cord stimulation population.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) motor symptoms. DBS is also associated with postoperative cognitive change in some patients. Previous studies found associations between medial active electrode contacts and overall cognitive decline. Our current aim is to determine the relationship between active electrode contact location and domain-specific cognitive changes. METHODS: A single-institution retrospective cohort study was conducted in patients with PD who underwent subthalamic nucleus (STN) DBS from August 05, 2010, to February 22, 2021, and received preoperative and postoperative neuropsychological testing. Standardized norm-referenced test z-scores were categorized into attention, executive function, language, verbal memory, and visuospatial domains. SD change scores were averaged to create domain-specific change scores. We identified anterior commissure/posterior commissure coordinates of active electrode contacts in atlas space. We evaluated differences in active electrode contact location between patients with a domain score decrease of at least 1 SD and less than 1 SD. We performed multiple variable linear regression controlling for age, sex, education, time from surgery to postoperative neuropsychological testing (follow-up duration), disease duration, preoperative unified Parkinson's disease rating scale off medication scores, and preoperative memory scores to determine the relationship between active electrode contact location and domain change. RESULTS: A total of 83 patients (male: n = 60, 72.3%) were included with a mean age of 63.6 ± 8.3 years, median disease duration of 9.0 [6.0, 11.5] years, and median follow-up duration of 8.0 [7.0, 11.0] months. More superior active electrode contact location in the left STN (P = .002) and higher preoperative memory scores (P < .0001) were associated with worsening memory. Active electrode contact location was not associated with change in other domains. CONCLUSION: In patients with PD who underwent STN DBS, we found an association between superior active electrode contacts in the left STN and verbal memory decline. Our study increases understanding of factors associated with cognitive change after DBS and may help inform postoperative programming.

In the feline model of the motor evoked potential (MEP) test, a multiphasic spinal cord signal can be elicited in response to bipolar or transcranial brain stimulation. Previous studies have shown that signals produced by threshold stimulation travel mostly in the corticospinal tract. However, from this study we show that suprathreshold stimulation produces very large amplitude MEPs which travel in the ventral funiculus and therefore are most likely associated with extrapyramidal tract activation. The data supporting this conclusion are: (1) apparent conduction velocities of the first two large amplitude peaks are at least 80 m/s with transcranial stimulation; (2) latency of the transcranial MEP at L2 in the cord is less than or equal to 3.50 ms; (3) large amplitude, positive monophasic potentials are recorded in the ventral but not dorsal-lateral funiculus for either bipolar or transcranial MEPs; (4) both bipolar and transcranial MEPs are significantly reduced or abolished by selective lesion of the ventral funiculus. The two tracts which we believe are responsible for mediating the suprathreshold MEP in the cat are the reticulospinal and vestibulospinal tracts. This is significant because suprathreshold MEPs can be used to monitor feline ventral cord function. Furthermore, combining the use of threshold and suprathreshold MEPs may provide a differential diagnostic test for pyramidal vs. extrapyramidal motor function.

OBJECTIVE:The deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5-4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial. MATERIALS AND METHODS:Attempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures. RESULTS:Twelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson's Disease Rating Scale [UPDRS]-IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; pinteraction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire-39 (PDQ-39), and levodopa equivalent daily dose (LEDD). CONCLUSIONS:Eleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016). CLINICAL TRIAL REGISTRATION:The Clinicaltrials.gov registration number for the study is NCT00282152.

Objective. The objectives of this study were to assess gait biomechanics and the effect of overground walking speed on gait parameters, kinematics, and electromyographic (EMG) activity in the hindlimb muscles of Yucatan minipigs (YMPs). Approach. Nine neurologically-intact, adult YMPs were trained to walk overground in a straight line. Whole-body kinematics and EMG activity of hindlimb muscles were recorded and analyzed at six different speed ranges (0.4-0.59, 0.6-0.79, 0.8-0.99, 1.0-1.19, 1.2-1.39, and 1.4-1.6 m s(-1)). A MATLAB program was developed to detect strides and gait events automatically from motion-captured data. The kinematics and EMG activity were analyzed for each stride based on the detected events. Main results. Significant decreases in stride duration, stance and swing times and an increase in stride length were observed with increasing speed. A transition in gait pattern occurred at the 1.0 m s(-1) walking speed. Significant increases in the range of motion of the knee and ankle joints were observed at higher speeds. Also, the points of minimum and maximum joint angles occurred earlier in the gait cycle as the walking speed increased. The onset of EMG activity in the biceps femoris muscle occurred significantly earlier in the gait cycle with increasing speed. Significance. YMPs are becoming frequently used as large animal models for preclinical testing and translation of novel interventions to humans. A comprehensive characterization of overground walking in neurologically-intact YMPs is provided in this study. These normative measures set the basis against which the effects of future interventions on locomotor capacity in YMPs can be compared.

Laser interstitial thermal therapy (LITT) guided by magnetic resonance imaging (MRI) is a minimally invasive treatment option to ablate epileptogenic tissue or focal lesions in drug-resistant epilepsy patients. LITT induces less tissue injury and reduces perioperative pain and length of hospital stay when compared to open surgery. Laser energy is delivered using a long, flexible optical fiber stereotactically placed into the parenchymal region or lesion. Once MRI verifies the probe position, ablation induces thermal coagulation and tissue destruction at the probe tip. Injury extent can then be tracked using MRI thermography. Thermal ablation of the amygdalohippocampal complex in mesial temporal lobe epilepsy (MTLE) is the most common use of LITT in epilepsy patients. Published studies suggest seizure free rates of approximately 50% after LITT for MTLE, which is less favorable than open resection. Some authors have noted improved outcomes in certain neuropsychological parameters after LITT compared to resection in MTLE, although these results are preliminary. Other potential uses of LITT in epilepsy surgery include the ablation of an epileptogenic tumor, tuber, cavernoma, focal cortical dysplasic lesion or hypothalamic hamartoma. It can also be used to complete a corpus callosotomy. Long-term seizure and neuropsychological outcomes must be investigated in future prospective studies, and a better understanding of complication rates and strategies for avoidance is needed. In the future, LITT is likely to be a prominent procedure for the treatment of drug-resistant epilepsy.

Objective To report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial. Methods The pilot was a prospective, single-blind clinical trial that randomized patients with early-stage PD (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) vs ODT alone (IDEG050016, NCT0282152, IRB040797). Participants who completed the 2-year trial participated in this observational follow-up study, which included annual outpatient visits through 5 years. This analysis includes 28 patients who were taking PD medications for 6 months to 4 years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models. Results Early STN DBS + ODT participants required lower levodopa equivalent daily doses (p = 0.04, β = −240 mg, 95% confidence interval [CI] −471 to −8) and had 0.06 times the odds of requiring polypharmacy at 5 years compared to early ODT participants (p = 0.01, odds ratio [OR] 0.06, 95% CI 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS + ODT participants were 0.21 times those of early ODT participants (p < 0.001, OR 0.21, 95% CI 0.09 to 0.45). The safety profile was similar between groups. Conclusions These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the Food and Drug Administration has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016). Classification of evidence This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.

Background: Thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS) is an effective therapy for medication-refractory essential tremor (ET). However, 13–40% of patients with an initially robust tremor efficacy lose this benefit over time despite reprogramming attempts. At our institution, a cohort of ET patients with VIM DBS underwent implantation of a second anterior (ventralis oralis anterior; VOA) DBS lead to permit “confined stimulation.” We sought to assess whether confined stimulation conferred additional tremor capture compared to VIM or VOA stimulation alone. Methods: Seven patients participated in a protocol-based programming session during which a video-recorded Fahn-Tolosa-Marin Part A (FTM-A) tremor rating scale was used in the following 4 DBS states: off stimulation, VIM stimulation alone, VOA stimulation alone, and dual lead (confined) stimulation. Results: The average (SD) baseline FTM-A off score was 17.6 (4.0). VIM stimulation alone lowered the average FTM-A total score to 6.9 (4.0). Confined stimulation further attenuated the tremor, reducing the total score to 5.7 (2.8). Conclusions: Confined thalamic DBS can provide additional symptomatic benefits in patients with unsatisfactory tremor control from VIM or VOA stimulation alone.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months ( p < 0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD.

ObjectivesDeep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task.Materials and MethodsWe used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states.ResultsDeep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli.ConclusionsThese results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction.

Executive Committee: François Alesch, Vienna Tipu Aziz, Oxford Jocelyne Bloch, Lausanne Serge Blond, Lille Jean Ciurea, Bucharest Angelo Franzini, Milano Miroslav Galanda, Banska Bystrica A. Gonçalves-Ferreira, Lisbon Jorge Guridi, Pamplona Kai Lehtimäki, Tampere Bengt Linderoth, Stockholm Roman Liscák, Prague Ruby Mahesparan, Bergen Ioannis Panourias, Athens Dirk van Roost, Gent Ali Savas, Ankara Pawel Sokal, Bydgoszcz Vladimir Shabalov, Moscow Michiel J. Staal, Groningen Istvan Valalik, Budapest Jürgen Voges, Magdeburg

BACKGROUND: Finding the optimal location for the implantation of the electrode in deep brain stimulation (DBS) surgery is crucial for maximizing the therapeutic benefit to the patient. Such targeting is challenging for several reasons, including anatomic variability between patients as well as the lack of consensus about the location of the optimal target.OBJECTIVE: To compare the performance of popular manual targeting methods against a fully automatic nonrigid image registration-based approach.METHODS: In 71 Parkinson disease subthalamic nucleus (STN)-DBS implantations, an experienced functional neurosurgeon selected the target manually using 3 different approaches: indirect targeting using standard stereotactic coordinates, direct targeting based on the patient magnetic resonance imaging, and indirect targeting relative to the red nucleus. Targets were also automatically predicted by using a leave-one-out approach to populate the CranialVault atlas with the use of nonrigid image registration. The different targeting methods were compared against the location of the final active contact, determined through iterative clinical programming in each individual patient.RESULTS: Targeting by using standard stereotactic coordinates corresponding to the center of the motor territory of the STN had the largest targeting error (3.69 mm), followed by direct targeting (3.44 mm), average stereotactic coordinates of active contacts from this study (3.02 mm), red nucleus-based targeting (2.75 mm), and nonrigid image registration-based automatic predictions using the CranialVault atlas (2.70 mm). The CranialVault atlas method had statistically smaller variance than all manual approaches.CONCLUSION: Fully automatic targeting based on nonrigid image registration with the use of the CranialVault atlas is as accurate and more precise than popular manual methods for STN-DBS.