Deep Brain Stimulation Research Research Articles

Bibliometric analysis on Deep Brain StimulationProcedures Conducted Between 2000-2023

Objective: Deep brain stimulation (DBS) is a treatment method that uses electrodes to stimulate the brain, affecting brain activity and potentially causing medical conditions. It is commonly used to treat Parkinson's disease, essential tremor, dystonia, epilepsy, Tourette syndrome, and obsessive-compulsive disorder. This bibliometric study examines advanced bibliometric parameters in articles published since 2000, focusing on trends in publishing organizations, countries, funding sources, international collaborations, and trend keywords. Materials and Methods: We have searched the Web of Science database to find articles on DBS which published since 2000. The search was performed by using the MESH keywords releated to "Deep brain stimulation". Results: This study presents a comprehensive analysis of 4,601 articles on Deep Brain Stimulation (DBS) from 2000 to 2023, focusing on publication trends, properties, funding, country contributions, and international collaborations. Noteworthy findings include a peak of 413 publications in 2020 and 14,992 citations in 2021. The overall trajectory demonstrates a significant increase in scientific output, with an average of 31.9 citations per article. Publication properties reveal diverse access categories, including 66 Early Access and 2,136 Open Access articles. The majority of records are in the Science Citation Index Expanded (93.980%). Clinical Neurology dominates research topics with 63.464% representation. Funding sources highlight major contributions from the USA, Germany, and China. The USA leads in research output, while the University of Toronto tops institutions. Major journals include "Stereotactic and Functional Neurosurgery" and "Movement Disorders." Keyword analysis emphasizes common themes like "deep brain stimulation" and "Parkinson's disease." International collaborations involve researchers from 75 countries, with the USA leading in total link strength. This study contributes valuable insights into the global landscape of DBS research. Conclusion: This analysis highlights the dynamic nature of Deep Brain Stimulation research, highlighting global collaboration and diverse topics, emphasizing the crucial role of key countries, institutions, and journals.

Why are clinical trials of deep brain stimulation terminated? An analysis of clinicaltrials.gov

BackgroundAlthough deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. ObjectiveTo review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. MethodsThe ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. ResultsOf 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. ConclusionOne in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.

Deep Brain Stimulation (DBS) in Treatment-Resistant Depression (TRD): Hope and Concern.

In this chapter, we explore the historical evolution, current applications, and future directions of Deep Brain Stimulation (DBS) for Treatment-Resistant Depression (TRD). We begin by highlighting the early efforts of neurologists and neurosurgeons who laid the foundations for today's DBS techniques, moving from controversial lobotomies to the precision of stereotactic surgery. We focus on the advent of DBS, emphasizing its emergence as a significant breakthrough for movement disorders and its extension to psychiatric conditions, including TRD. We provide an overview of the neural networks implicated in depression, detailing the rationale for the choice of common DBS targets. We also cover the technical aspects of DBS, from electrode placement to programming and parameter selection. We then critically review the evidence from clinical trials and open-label studies, acknowledging the mixed outcomes and the challenges posed by placebo effects and trial design. Safety and ethical considerations are also discussed. Finally, we explore innovative directions for DBS research, including the potential of closed-loop systems, dual stimulation strategies, and noninvasive alternatives like ultrasound neuromodulation. In the last section, we outline recommendations for future DBS studies, including the use of alternative designs for placebo control, the collection of neural and behavioral recordings, and the application of machine-learning approaches.

Publication Rates and Characteristics of Clinical Trials in Deep Brain and Responsive Neurostimulation

Introduction: Prompt dissemination of clinical trial results is essential for ensuring the safety and efficacy of intracranial neurostimulation treatments, including deep brain stimulation (DBS) and responsive neurostimulation (RNS). However, the frequency and completeness of results publication, and reasons for reporting delays, are unknown. Moreover, the patient populations, targeted anatomical locations, and stimulation parameters should be clearly reported for both reproducibility and to identify lacunae in trial design. Here, we examine DBS and RNS trials from 1997 to 2022, chart their characteristics, and examine rates and predictors of results reporting. Methods: Trials were identified using <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>. Associated publications were identified using <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://PubMed.gov" xmlns:xlink="http://www.w3.org/1999/xlink">PubMed.gov</ext-link>. Pearson’s χ² tests were used to assess differences in trial characteristics between published and unpublished trials. Results: Across 449 trials, representing a cumulative cohort of 42,769 patient interventions, there were 37 therapeutic indications and 44 stimulation targets. The most common indication and target were Parkinson’s disease (40.55%) and the subthalamic nucleus (35.88%), respectively. Only 0.89% of trials were in pediatric patients (11.58% were mixed pediatric and adult). Explored targets represented 75% of potential basal ganglia targets but only 29% of potential thalamic targets. Allowing a 1-year grace period after trial completion, 34/169 (20.12%) had results reported on <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, and 107/169 (63.31%) were published. ∼80% of published trials included details about stimulation parameters used. Published and unpublished trials did not significantly differ by trial characteristics. Conclusion: We highlight key knowledge and performance gaps in DBS and RNS trial research. Over one-third of trials remain unpublished >1 year after completion; pediatric trials are scarce; most of the thalamus remains unexplored; about one-in-five trials fail to report stimulation parameters; and movement disorders comprise the most studied indications.

Treating addiction with deep brain stimulation: Ethical and legal considerations.

The use of neuromodulation in the treatment of psychiatric conditions is controversial despite its lengthy history. This particularly applies to the use of invasive neuromodulation, such as deep brain stimulation (DBS), to treat substance use disorder (SUD) due to the considerable risks of the procedures. However, given the advances in DBS research and the shortcomings of current treatment modalities for addiction, off-label use and clinical trials are being implemented for the management of treatment-refractory patients. Here we conduct an ethical and legal analysis of DBS for SUD, referencing the four foundational principles of medical ethics and key legal concepts. There are major concerns related to the capacity of a SUD patient to provide informed consent, as well as the risks and benefits of DBS compared to traditional treatment methods. In addition to ethical concerns, we explore potential legal issues that may arise from DBS in the treatment of addiction. These include the potential mandate of these procedures in the context of the criminalization of substance use, and the issue of familial consent in the decision-making process. Given the paucity of relevant clinical guidelines or legal cases, general medico-legal principles serve as the reference in making decisions about the responsible use of DBS as a treatment for addiction. Given the rapidly increasing evidence for DBS as a treatment for SUD, it is an urgent imperative to consider the relevant key ethical and legal issues. Incorporating IDEAL (Idea, Development, Exploration, Assessment, Long-term follow-up) framework into future research in DBS is recommended to evaluate patient safety and ethical perspectives. With the broad criminalization of SUD across the globe, legal coercion of DBS is not impossible, especially if proven to be effective to treat SUD. It is advised for stakeholders to urgently consider incorporating DBS-related drug policies so that the potential benefits of DBS within the rights of people with SUD are not hindered by the lack of clinical guidance and legislations.

Deep Brain Stimulation: Emerging Tools for Simulation, Data Analysis, and Visualization.

Deep brain stimulation (DBS) is a well-established neurosurgical procedure for movement disorders that is also being explored for treatment-resistant psychiatric conditions. This review highlights important consideration for DBS simulation and data analysis. The literature on DBS has expanded considerably in recent years, and this article aims to identify important trends in the field. During DBS planning, surgery, and follow up sessions, several large data sets are created for each patient, and it becomes clear that any group analysis of such data is a big data analysis problem and has to be handled with care. The aim of this review is to provide an update and overview from a neuroengineering perspective of the current DBS techniques, technical aids, and emerging tools with the focus on patient-specific electric field (EF) simulations, group analysis, and visualization in the DBS domain. Examples are given from the state-of-the-art literature including our own research. This work reviews different analysis methods for EF simulations, tractography, deep brain anatomical templates, and group analysis. Our analysis highlights that group analysis in DBS is a complex multi-level problem and selected parameters will highly influence the result. DBS analysis can only provide clinically relevant information if the EF simulations, tractography results, and derived brain atlases are based on as much patient-specific data as possible. A trend in DBS research is creation of more advanced and intuitive visualization of the complex analysis results suitable for the clinical environment.

Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder and Treatment-Resistant Depression.

In deep brain stimulation (DBS), a neurostimulation device is implanted to generate electrical fields in targeted deep brain regions in order to affect circuits associated with neuropsychiatric illness for potential therapeutic benefit. The development of DBS has followed a decades-long history of psychiatric neurosurgery, with advances in pacemakers and spinal neurostimulation devices allowing for the use of DBS in the treatment of neuropsychiatric disorders. Currently, deep brain stimulation for psychiatric illness has been approved by the U.S. Food and Drug Administration for the treatment of intractable obsessive-compulsive disorder, through a Humanitarian Device Exemption. The use of DBS for treatment-resistant depression is another promising application of this technology. Several potential targets of DBS have shown promise for treating neuropsychiatric illness, but few have demonstrated efficacy in randomized controlled trials. Future directions for DBS research will likely include modified trial designs, refined targets, the use of tractography for more specific and individualized targeting, and development of closed-loop DBS.

The software defined implantable modular platform (STELLA) for preclinical deep brain stimulation research in rodents

Context. Long-term deep brain stimulation (DBS) studies in rodents are of crucial importance for research progress in this field. However, most stimulation devices require jackets or large head-mounted systems which severely affect mobility and general welfare influencing animals’ behavior. Objective. To develop a preclinical neurostimulation implant system for long-term DBS research in small animal models. Approach. We propose a low-cost dual-channel DBS implant called software defined implantable platform (STELLA) with a printed circuit board size of Ø13 × 3.3 mm, weight of 0.6 g and current consumption of 7.6 µA/3.1 V combined with an epoxy resin-based encapsulation method. Main results. STELLA delivers charge-balanced and configurable current pulses with widely used commercial electrodes. While in vitro studies demonstrate at least 12 weeks of error-free stimulation using a CR1225 battery, our calculations predict a battery lifetime of up to 3 years using a CR2032. Exemplary application for DBS of the subthalamic nucleus in adult rats demonstrates that fully-implanted STELLA neurostimulators are very well-tolerated over 42 days without relevant stress after the early postoperative phase resulting in normal animal behavior. Encapsulation, external control and monitoring of function proved to be feasible. Stimulation with standard parameters elicited c-Fos expression by subthalamic neurons demonstrating biologically active function of STELLA. Significance. We developed a fully implantable, scalable and reliable DBS device that meets the urgent need for reverse translational research on DBS in freely moving rodent disease models including sensitive behavioral experiments. We thus add an important technology for animal research according to ‘The Principle of Humane Experimental Technique’—replacement, reduction and refinement (3R). All hardware, software and additional materials are available under an open source license.

Electrophysiological biomarkers for deep brain stimulation outcomes in movement disorders: state of the art and future challenges

Several neurological diseases are accompanied by rhythmic oscillatory dysfunctions in various frequency ranges and disturbed cross-frequency relationships on regional, interregional, and whole brain levels. Knowledge of these disease-specific oscillopathies is important mainly in the context of deep brain stimulation (DBS) therapy. Electrophysiological biomarkers have been used as input signals for adaptive DBS (aDBS) as well as preoperative outcome predictors. As movement disorders, particularly Parkinson's disease (PD), are among the most frequent DBS indications, the current research of DBS is the most advanced in the movement disorders field. We reviewed the literature published mainly between 2010 and 2020 to identify the most important findings concerning the current evolution of electrophysiological biomarkers in DBS and to address future challenges for prospective research.

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank.

Perceptions of Deep Brain Stimulation for Adolescents with Obsessive-Compulsive Disorder.

Objective: The present study aims to understand perceptions of deep brain stimulation (DBS) for severe obsessive-compulsive disorder (OCD) in adolescents among two groups: parents of children with a history of OCD and adults with a history of OCD. Methods: Two hundred sixty participants completed a questionnaire exploring their treatment history, relevant symptom severity, DBS knowledge, and DBS attitudes using an acceptability scale and a series of statements indicating levels of willingness or reluctance to consider DBS for adolescents with severe OCD or severe epilepsy. Results: Overall, participants found DBS to be fairly acceptable for adolescents with severe OCD, with 63% reporting at least 7/10 on a 0-10 acceptability Likert scale. Respondents were more willing to consider DBS for epilepsy than for OCD. Several factors were associated with greater willingness to consider DBS for OCD, including familiarity with DBS, the presence of suicidal thoughts, assurances of daily functioning improvements, and assurances of substantial symptom reduction. Concerns about safety, personality changes, and long-term effects on the body were associated with greatest reluctance to consider DBS for OCD. Conclusions: Our findings support the importance of increasing parents' familiarity with DBS, monitoring factors participants identified as most important to their DBS perceptions in future DBS research, and communicating benefits and risks clearly. We also highlight the need for further research on perceptions of DBS for severe and refractory OCD in adolescents.

Deep-Brain Stimulation for Essential Tremor and Other Tremor Syndromes: A Narrative Review of Current Targets and Clinical Outcomes.

Tremor is a prevalent symptom associated with multiple conditions, including essential tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (ventral intermediate nucleus of the thalamus (Vim), prelemniscal radiations (Raprl), caudal zona incerta (Zi), thalamus (Vo) and subthalamic nucleus (STN)) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

Publication of Study Exit Procedures in Clinical Trials of Deep Brain Stimulation: A Focused Literature Review.

Considerable variability exists in the publication of clinical research study procedures related to study enrollment and participant exit from clinical trials. Despite recent efforts to encourage research data sharing and greater transparency regarding research outcomes, reporting of research procedures remains inconsistent. Transparency about study procedures has important implications for the interpretation of study outcomes and the consistent implementation of best practices in clinical trial design and conduct. This review of publications from clinical trials of deep brain stimulation (DBS) using the MEDLINE database examines the frequency and consistency of publication of research procedures and data related to exit from DBS research. Related considerations, such as device explant or continued use, battery and other device hardware replacements, and post-trial follow-up care are also reviewed. This review finds significant variability in the publication and reporting of study exit procedures. Of the 47 clinical trials included in this review, 19% (9) disclosed procedures related to exit from research. Reporting of other exit-related data and study procedures examined in this review was identified in fewer than half of the included clinical trials. The rate of participant retention and duration of follow-up was reported more than any other category of data included in this review. Results inform efforts to improve consistency in research design, conduct, and publication of results from clinical trials in DBS and related areas of clinical research.

Mobile Application for Parkinson's Disease Deep Brain Stimulation (MAP DBS): An Open-Label, Multicenter, Randomized, Controlled Clinical Trial

Mobile Application for Parkinson's Disease Deep Brain Stimulation (MAP DBS): An Open-Label, Multicenter, Randomized, Controlled Clinical Trial

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle.

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment-resistant depressed patients-one of several targets under investigation-has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.

An International Survey of Deep Brain Stimulation Utilization in Asia and Oceania: The DBS Think Tank East.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania.Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India.Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited.Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases.

A novel low-cost electrode for recording the local field potential of freely moving rat's brain.

Local field potentials (LFPs) are involved in almost all cognitive activities of animals. Several kinds of recording electrodes are used for recording LFPs in freely moving animals, including commercial and homemade electrodes. However, commercial recording electrodes are expensive, and their relatively fixed size often causes a steric hindrance effect, especially when combining deep brain stimulation (DBS) with LFP recording, which may not always satisfy the aim of researchers. Currently, an increasing number of researchers are designing their own recording electrodes to lower research costs. Nevertheless, there is no simple universal method to produce low-cost recording electrodes with a specific size according to the target brain area. Thus, we developed a simple method for quickly producing low-cost multiple-channel recording electrodes. To inspect the effectiveness of our self-designed electrode, LFPs were recorded in a Parkinson’s disease (PD) rat model, and an electrical stimulation electrode was implanted into the subthalamic nucleus to verify the space-saving ability of the self-designed recording electrode. The results showed that <30 min was needed to prepare an electrode and that the electrode materials cost <5 dollars. Further investigations showed that our electrode successfully recorded the beta oscillations (12–40 Hz) in the PD rat model. Thus, this method will greatly reduce the cost of recording electrodes and save time for researchers. Additionally, the small size of the electrode will further facilitate DBS research.

Proceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology.

The Seventh Annual Deep Brain Stimulation (DBS) Think Tank held on September 8th of 2019 addressed the most current: (1) use and utility of complex neurophysiological signals for development of adaptive neurostimulation to improve clinical outcomes; (2) Advancements in recent neuromodulation techniques to treat neuropsychiatric disorders; (3) New developments in optogenetics and DBS; (4) The use of augmented Virtual reality (VR) and neuromodulation; (5) commercially available technologies; and (6) ethical issues arising in and from research and use of DBS. These advances serve as both “markers of progress” and challenges and opportunities for ongoing address, engagement, and deliberation as we move to improve the functional capabilities and translational value of DBS. It is in this light that these proceedings are presented to inform the field and initiate ongoing discourse. As consistent with the intent, and spirit of this, and prior DBS Think Tanks, the overarching goal is to continue to develop multidisciplinary collaborations to rapidly advance the field and ultimately improve patient outcomes.

Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics.

The annual deep brain stimulation (DBS) Think Tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. The proceedings of the Sixth Annual Think Tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging techniques for the treatment of a range of psychiatric and neurological conditions including Parkinson’s disease, essential tremor, Tourette syndrome, epilepsy, cognitive disorders, and addiction. Each section of this overview provides insight about the understanding of neuromodulation for specific disease and discusses current challenges and future directions. This year’s report addresses key issues in implementing advanced neurophysiological techniques, evolving use of novel modulation techniques to deliver DBS, ans improved neuroimaging techniques. The proceedings also offer insights into the new era of brain network neuromodulation and connectomic DBS to define and target dysfunctional brain networks. The proceedings also focused on innovations in applications and understanding of adaptive DBS (closed-loop systems), the use and applications of optogenetics in the field of neurostimulation and the need to develop databases for DBS indications. Finally, updates on neuroethical, legal, social, and policy issues relevant to DBS research are discussed.

A Driving-Force Predictor for Estimating Pathway Activation in Patient-Specific Models of Deep Brain Stimulation

Detailed biophysical modeling of deep brain stimulation (DBS) provides a theoretical approach to quantify the cellular response to the applied electric field. However, the most accurate models for performing such analyses, patient-specific field-cable (FC) pathway-activation models (PAMs), are so technically demanding to implement that their use in clinical research is greatly limited. Predictive algorithms can simplify PAM calculations, but they generally fail to reproduce the output of FC models when evaluated over a wide range of clinically relevant stimulation parameters. Therefore, we set out to develop a novel driving-force (DF) predictive algorithm (DF-Howell), customized to the study of DBS, which can better match FC results. We developed the DF-Howell algorithm and compared its predictions to FC PAM results, as well as to the DF-Peterson algorithm, which is currently the most accurate and generalizable DF-based method. Comparison of the various methods was quantified within the context of subthalamic DBS using activation thresholds of axons representing the internal capsule, hyperdirect pathway, and cerebellothalamic tract for various combinations of fiber diameters, stimulus pulse widths, and electrode configurations. The DF-Howell predictor estimated activation of the three axonal pathways with less than a 6.2% mean error with respect to the FC PAM for all 21 cases tested. In 15 of the 21 cases, DF-Howell outperformed DF-Peterson in estimating pathway activation, reducing mean-errors up to 22.5%. DF-Howell represents an accurate predictor for estimating axonal pathway activation in patient-specific DBS models, but errors still exist relative to FC PAM calculations. Nonetheless, the tractability of DF algorithms helps to reduce the technical barriers for performing accurate biophysical modeling in clinical DBS research studies.