Search

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9–11, 2023 in Gainesville, Florida with the theme of “Pushing the Forefront of Neuromodulation”. The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.

Deep brain stimulators (DBS) may fail for a multitude of reasons. We present a 79-year-old Parkinson's disease patient who suffered a DBS failure following impulse generator (IPG) replacement surgery due to the IPG flipping within an expanded capsular pocket. This creation of the pocket was unintentional, and the pocket formed around an undiagnosed postoperative hemorrhage. The syndrome could be considered “Twiddler-like” because it resulted in device flipping. There were, however, many characteristic differences between our case and classical Twiddler's syndrome. DBS neurostimulator failure due to hematoma induced device flipping should be suspected when device interrogation is impossible or there are abnormally high impedances across multiple DBS lead contacts. A plain film X-ray series should be ordered and can be useful in providing radiological evidence of device flipping. In cases like ours the extensive braiding encountered in Twiddler's syndrome may be absent. Anchoring the IPG to a deep fascial layer as well as the use of an antimicrobial pouch are two methods that may be employed to prevent or to treat this complication.

Introduction: Myriad disorders cause right ventricular (RV) dilation and lead to tricuspid regurgitation (TR). Because the thin-walled, flexible RV is mechanically coupled to the pulmonary circulation and the left ventricular septum, it distorts with any disturbance in the cardiopulmonary system. TR, therefore, can result from pulmonary hypertension, left heart failure, or intrinsic RV dysfunction; but once it occurs, TR initiates a cycle of worsening RV volume overload, potentially progressing to right heart failure. Characteristic three-dimensional RV shape-changes from this process, and changes particular to individual TR causes, have not been defined in detail.Methods: Cardiac MRI was obtained in 6 healthy volunteers, 41 patients with ≥ moderate TR, and 31 control patients with cardiac disease without TR. The mean shape of each group was constructed using a three-dimensional statistical shape model via the particle-based shape modeling approach. Changes in shape were examined across pulmonary hypertension and congestive heart failure subgroups using principal component analysis (PCA). A logistic regression approach based on these PCA modes identified patients with TR using RV shape alone.Results: Mean RV shape in patients with TR exhibited free wall bulging, narrowing of the base, and blunting of the RV apex compared to controls (p

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.

This research study provides patient and caregiver perspectives as to whether or not to undergo adaptive deep brain stimulation (aDBS) research. A total of 51 interviews were conducted in a multi-site study including patients undergoing aDBS and their respective caregivers along with persons declining aDBS. Reasons highlighted for undergoing aDBS included hopes for symptom alleviation, declining quality of life, desirability of being in research, and altruism. The primary reasons for not undergoing aDBS issues were practical rather than specific to aDBS technology, although some persons highlighted a desire to not be the first to trial the new technology. These themes are discussed in the context of “push” factors wherein any form of surgical intervention is preferable to none and “pull” factors wherein opportunities to contribute to science combine with hopes and/or expectations for the alleviation of symptoms. We highlight the significance of study design in decision making. aDBS is an innovative technology and not a completely new technology. Many participants expressed value in being part of research as an important consideration. We suggest that there are important implications when comparing patient perspectives vs. theoretical perspectives on the choice for or against aDBS. Additionally, it will be important how we communicate with patients especially in reference to the complexity of study design. Ultimately, this study reveals that there are benefits and potential risks when choosing a research study that involves implantation of a medical device.

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.

Background: Treating medication-refractory freezing of gait (FoG) in Parkinson’s disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS).Methods: In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

ObjectiveTo investigate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi), deep brain stimulation (DBS) on individual action tremor/postural tremor (AT) and rest tremor (RT) in Parkinson’s disease (PD). Randomized DBS studies have reported marked benefit in tremor with both GPi and STN and DBS, however, there is a paucity of information available on AT vs RT when separated by the surgical target.MethodsWe retrospectively reviewed the 1-year clinical outcome of PD patients treated with STN and GPi DBS at the University of Florida. We specifically selected patients with moderate to severe AT. Eighty-eight patients (57 STN and 31 GPi) were evaluated at 6 and 12 months for changes in AT and RT in the OFF-medication/ON stimulation state. A comparison of “response” was performed and defined as greater than or equal to a 2-point decrease in tremor score.ResultsSTN and GPi DBS both improved AT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). The STN DBS group experienced a greater improvement in AT at 6 months compared to the GPi group (p = 0.005) but not at the 12 months follow-up (p = 0.301). Both STN and GPi DBS also improved RT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). There was no difference in RT scores between the two groups at 6 months (p = 0.23) or 12 months (p = 0.74). The STN group had a larger proportion of patients who achieved a “response” in AT at 6 months (p < 0.01), however, this finding was not present at 12 months (p = 0.23). A sub-analysis revealed that in RT, the STN group had a larger percentage of “responders” when followed through 12 months (p < 0.01).ConclusionBoth STN and GPi DBS reduced PD associated AT and RT at 12 months follow-up. There was no advantage of either brain target in the management of RT or AT. One nuance of the study was that STN DBS was more effective in suppressing AT in the early postoperative period, however, this effect diminished over time. Clinicians should be aware that it may take longer to achieve a similar tremor outcome when utilizing the GPi target.

To more efficiently communicate the results of neuropsychological assessment to interdisciplinary teams, the University of Florida Neuropsychology Service developed a Deep Brain Stimulation-Cognitive Rating Scale (DBS-CRS). This tool condensed results of a 3-h exam into a five-point scale ranging from 1 (least) to 5 (most) cognitive concern for DBS surgery. In this study, we evaluated the role of the DBS-CRS in clinical decisions by the interdisciplinary team to proceed to surgery, its relationship to objective neuropsychological scores, and its predictive utility for clinical outcome. We retrospectively examined 189 patients with Parkinson’s disease who were evaluated for DBS candidacy (mean age 64.8 [SD 9.2], disease duration 8.9 years [SD 5.0], UPDRS-Part III off medication 38.5 [SD 10.5], Dementia Rating Scale-II 135.4 [SD 6.0]). Approximately 19% of patients did not proceed to surgery, with neuropsychological red flags being the most commonly documented reason (57%). Patients who underwent DBS surgery had significantly better DBS-CRS scores than those who did not (p < 0.001). The two strongest and unique neuropsychological contributors to DBS-CRS ratings were delayed memory and executive function, followed by language and visuoperception, based on hierarchical linear regression that accounted for 77.2% of the variance. In terms of outcome, DBS-CRS scores were associated with higher quality of life, less severe motor symptoms, and better daily functioning 6 months following DBS surgery. Together, these findings support the construct and predictive validity of the DBS-CRS as a concise tool for effectively communicating pre-DBS cognitive concerns to an interdisciplinary team, thereby aiding decision making in potential DBS candidates.

This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson’s disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1–8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD.Clinical Trial Registration:Clinicaltrials.gov identifier; NCT02318927.

Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort.Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as 30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline.Conclusion: Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.

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.

Objective: To examine the short- and long-term clinical outcomes of the bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on gait and axial symptoms in Parkinson’s disease (PD) patients. Available data have been inconsistent and mostly short-term regarding the effect of both brain targets on gait and axial symptoms. We aimed to identify potential target specific differences at 3-year follow-up from a large single-center experience.Methods: We retrospectively reviewed short-term (6-month follow-up) and long-term (36-month follow-up) changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and III total scores of 72 PD patients (53 with bilateral STN-DBS and 19 with bilateral GPi-DBS). An interdisciplinary team made target-specific decisions for each DBS patient. We analyzed changes in gait and axial subscores derived from UPDRS II and III.Results: In both the STN- and GPi-DBS cohorts, we observed no significant differences in gait and axial UPDRS derived subscores in the off-med/on stimulation state at long-term follow-up when compared to baseline. On-med axial scores remained similar in the short-term but worsened in both groups (STN, 2.23 ± 3.43, p < 0.001; GPi, 2.53 ± 2.37, p < 0.01) in the long-term possibly due to disease progression. At long-term follow-up, the UPDRS III off-med/on stimulation scores worsened but were persistently improved from baseline in both groups (−9.07 ± 13.9, p < 0.001).Conclusions: The study showed that long-term both STN- and GPi-DBS had a similar effect on gait and axial symptoms in UPDRS derived subscores at 36-month follow-up despite potential baseline differences in criteria for selection of each target. More sophisticated measures of gait and balance beyond the categorical UPDRS score will be needed for future studies.

BackgroundConventional Parkinson’s disease (PD) deep brain stimulation (DBS) utilizes a pulse with an active phase and a passive charge-balancing phase. A pulse-shaping strategy that eliminates the passive phase may be a promising approach to addressing movement disorders.ObjectivesThe current study assessed the safety and tolerability of square biphasic pulse shaping (sqBIP) DBS for use in PD.MethodsThis small pilot safety and tolerability study compared sqBiP versus conventional DBS. Nine were enrolled. The safety and tolerability were assessed over a 3-h period on sqBiP. Friedman’s test compared blinded assessments at baseline, washout, and 30 min, 1 h, 2 h, and 3 h post sqBIP.ResultsBiphasic pulses were safe and well tolerated by all participants. SqBiP performed as well as conventional DBS without significant differences in motor scores nor accelerometer or gait measures.ConclusionBiphasic pulses were well-tolerated and provided similar benefit to conventional DBS. Further studies should address effectiveness of sqBIP in select PD patients.

Although the basal ganglia have been implicated in a growing list of human behaviors, they include some of the least understood nuclei in the brain. For several decades studies have employed numerous methodologies to uncover evidence pointing to the basal ganglia as a hub of both motor and non-motor function. Recently, new electrophysiological characterization of the basal ganglia in humans has become possible through direct access to these deep structures as part of routine neurosurgery. Electrophysiological approaches for identifying non-motor function have the potential to unlock a deeper understanding of pathways that may inform clinical interventions and particularly neuromodulation. Various electrophysiological modalities can also be combined to reveal functional connections between the basal ganglia and traditional structures throughout the neocortex that have been linked to non-motor behavior. Several reviews have previously summarized evidence for non-motor function in the basal ganglia stemming from behavioral, clinical, computational, imaging, and non-primate animal studies; in this review, instead we turn to electrophysiological studies of non-human primates and humans. We begin by introducing common electrophysiological methodologies for basal ganglia investigation, and then we discuss studies across numerous non-motor domains–emotion, response inhibition, conflict, decision-making, error-detection and surprise, reward processing, language, and time processing. We discuss the limitations of current approaches and highlight the current state of the information.