Directional Deep Brain Stimulation Research Articles

Effect of Directional Deep Brain Stimulation on Sensory Thresholds in Parkinson's Disease.

ObjectivePrevious studies showed that deep brain stimulation (DBS) relieves pain symptoms in Parkinson disease (PD) patients when programmed for motor-symptom relief. One factor involved in pain processing is sensory perception of stimuli. With the advent of directional leads, we explore whether directional DBS affects quantitative sensory testing (QST) metrics acutely.MethodsPD patients with subthalamic (STN) DBS and directional leads were tested in 5 settings (DBS-OFF, DBS-ON with omnidirectional stimulation, and DBS-ON) for each of three directional segments of contact used for clinical programming. The Unified Parkinson’s Disease Rating Scale (UPDRS-III) assessed patient’s motor skills at time of study visit at clinical contact and at contact which produced optimal sensory threshold (defined by the greatest tolerance to mechanical stimuli). Correlation analyses were performed between stimulation parameters [amplitude, frequency, pulse width (PW), total electrical energy delivered (TEED)] and outcome metrics.ResultsSensory thresholds were obtained in nine patients. Directional stimulation did not significantly alter patient perceptions of sensory stimulus [cold pain (p = 0.69), warm pain (p = 0.99), Von frey fibers (p = 0.09), pin-prick (p = 0.88), vibration (p = 0.40), pressure (p = 0.98)]. With correlation analysis, increasing PW at the posterior contact increased pin prick and vibration sensitivity (p < 0.001). Additionally, an increase in TEED caused a decrease in sensitivity to warm detection when using the anterior (p = 0.04), lateral (p = 0.02), and medial contacts (p = 0.03), and also caused a decrease in sensitivity to cold detection when using the medial contact (p = 0.03). UPDRS-III remained stable during testing.ConclusionMotor benefit can be acutely maintained at directional contacts, whereas directional stimulation can modulate thermal and mechanical sensitivity. Further investigation will determine whether these changes are maintained chronically or can be improved with optimized programming.

Bipolar Directional Deep Brain Stimulation in Essential and Parkinsonian Tremor

To compare directional monopolar, bipolar, and directional bipolar thalamic deep brain stimulation (DBS) in tremor patients. Fourteen tremor patients (7 Essential Tremor and 7 Parkinson's Disease) implanted with directional DBS electrodes in the ventral intermediate nucleus (VIM) were enrolled. Side-effect thresholds of monopolar directional stimulation (DIRECT) were compared to circular DBS as well as, in a randomized design, to those of two different bipolar stimulation settings (BIPOLAR = circular anode; BI-DIRECT = directional anode). Tremor suppression (Tremor Rating Scale, TRS) right below the side-effect threshold was also assessed. Directional DBS in the individually best direction showed higher side-effect thresholds than circular DBS (p = 0.0063). The thresholds were raised further using either one of the bipolar stimulation paradigms (BIPOLAR p = 0.0029, BI-DIRECT p = 0.0022). The side-effect thresholds did not differ between both bipolar settings, but side-effects were less frequent with BI-DIRECT. No difference in TRS scores with stimulation just below the side-effect threshold was found between all stimulation conditions. Side-effect thresholds of monopolar directional and bipolar stimulation with both circular and directional anodes were higher compared to traditional monopolar circular stimulation in the VIM. Bipolar DBS with directional anodes evoked side-effect less frequently than bipolar and monopolar directional stimulation. All stimulation settings had comparable effects on tremor suppression just below their side-effect thresholds. Thus, directional and different bipolar settings should be explored in patients with bothersome side-effects of thalamic stimulation when monopolar stimulation settings are not satisfying. Further studies are needed to explore the efficiency of the different bipolar stimulation paradigms.

Comparing Current Steering Technologies for Directional Deep Brain Stimulation Using a Computational Model That Incorporates Heterogeneous Tissue Properties

ObjectiveA computational model that accounts for heterogeneous tissue properties was used to compare multiple independent current control (MICC), multi‐stim set (MSS), and concurrent activation (co‐activation) current steering technologies utilized in deep brain stimulation (DBS) on volume of tissue activated (VTA) and power consumption.MethodsA computational model was implemented in Sim4Life v4.0 with the multimodal image‐based detailed anatomical (MIDA) model, which accounts for heterogeneous tissue properties. A segmented DBS lead placed in the subthalamic nucleus (STN). Three milliamperes of current (with a 90 μs pseudo‐biphasic waveform) was distributed between two electrodes with various current splits. The laterality, directional accuracy, volume, and shape of the VTAs using MICC, MSS and co‐activation, and their power consumption were computed and compared.ResultsMICC, MSS, and coactivation resulted in less laterality of steering than single‐segment activation. Both MICC and MSS show directional inaccuracy (more pronounced with MSS) during radial current steering. Co‐activation showed greater directional accuracy than MICC and MSS at centerline between the two activated electrodes. MSS VTA volume was smaller and more compact with less current spread outside the active electrode plane than MICC VTA. There was no consistent pattern of power drain between MSS and MICC, but electrode co‐activation always used less power than either fractionating paradigm.ConclusionWhile current fractionalization technologies can achieve current steering between two segmented electrodes, this study shows that there are important limitations in accuracy and focus of tissue activation when tissue heterogeneity is accounted for.

Functional Use of Directional Local Field Potentials in the Subthalamic Nucleus Deep Brain Stimulation

BackgroundDirectional deep brain stimulation (DBS) technology aims to address the limitations, such as stimulation-induced side effects, by delivering selective, focal modulation via segmented contacts. However, DBS programming becomes more complex and time-consuming for clinical feasibility. Local field potentials (LFPs) might serve a functional role in guiding clinical programming.ObjectiveIn this pilot study, we investigated the spectral dynamics of directional LFPs in subthalamic nucleus (STN) and their relationship to motor symptoms of Parkinson’s disease (PD).MethodsWe recorded intraoperative STN-LFPs from 8-contact leads (Infinity-6172, Abbott Laboratories, Illinois, United States) in 8 PD patients at rest. Directional LFPs were referenced to their common average and time-frequency analysis was computed using a modified Welch periodogram method. The beta band (13–35 Hz) features were extracted and their correlation to preoperative UPDRS-III scores were assessed.ResultsNormalized beta power (13–20 Hz) and normalized peak power (13–35 Hz) were found to be higher in anterior direction despite lack of statistical significance (p > 0.05). Results of the Spearman correlation analysis demonstrated positive trends with bradykinesia/rigidity in dorsoanterior direction (r = 0.659, p = 0.087) and with axial scores in the dorsomedial direction (r = 0.812, p = 0.072).ConclusionGiven that testing all possible combinations of contact pairs and stimulation parameters is not feasible in a single clinic visit, spatio-spectral LFP dynamics obtained from intraoperative recordings might be used as an initial marker to select optimal contact(s).

Current Directions in Deep Brain Stimulation for Parkinson's Disease-Directing Current to Maximize Clinical Benefit.

Several single-center studies and one large multicenter clinical trial demonstrated that directional deep brain stimulation (DBS) could optimize the volume of tissue activated (VTA) based on the individual placement of the lead in relation to the target. The ability to generate axially asymmetric fields of stimulation translates into a broader therapeutic window (TW) compared to conventional DBS. However, changing the shape and surface of stimulating electrodes (directional segmented vs. conventional ring-shaped) also demands a revision of the programming strategies employed for DBS programming. Model-based approaches have been used to predict the shape of the VTA, which can be visualized on standardized neuroimaging atlases or individual magnetic resonance imaging. While potentially useful for optimizing clinical care, these systems remain limited by factors such as patient-specific anatomical variability, postsurgical lead migrations, and inability to account for individual contact impedances and orientation of the systems of fibers surrounding the electrode. Alternative programming tools based on the functional assessment of stimulation-induced clinical benefits and side effects allow one to collect and analyze data from each electrode of the DBS system and provide an action plan of ranked alternatives for therapeutic settings based on the selection of optimal directional contacts. Overall, an increasing amount of data supports the use of directional DBS. It is conceivable that the use of directionality may reduce the need for complex programming paradigms such as bipolar configurations, frequency or pulse width modulation, or interleaving. At a minimum, stimulation through directional electrodes can be considered as another tool to improve the benefit/side effect ratio. At a maximum, directionality may become the preferred way to program because of its larger TW and lower energy consumption.Electronic supplementary materialThe online version of this article (10.1007/s40120-020-00181-9) contains supplementary material, which is available to authorized users.

Directional deep brain stimulation leads reveal spatially distinct oscillatory activity in the globus pallidus internus of Parkinson's disease patients

The goal of this study was to characterize the spectral characteristics and spatial topography of local field potential (LFP) activity in the internal segment of the globus pallidus (GPi) in patients with Parkinson's disease utilizing directional (segmented) deep brain stimulation (dDBS) leads. Data were collected from externalized dDBS leads of three patients with idiopathic Parkinson's disease after overnight withdrawal of parkinsonian medication at rest and during a cued reach-to-target task. Oscillatory activity across lead contacts/segments was examined in the context of lead locations and contact orientations determined using co-registered preoperative 7 Tesla (T) MRI and postoperative CT scans. Each of the three patients displayed a unique frequency spectrum of oscillatory activity in the pallidum, with prominent peaks ranging from 5 to 35 Hz, that modulated variably across subjects during volitional movement. Despite subject-specific spectral profiles, a consistent finding across patients was that oscillatory power was strongest and had the largest magnitude of modulation during movement in LFPs recorded from segments facing the postero-lateral “sensorimotor” region of GPi, whereas antero-medially-directed segmented contacts facing the internal capsule and/or anterior GPi, had relatively weaker LFP power and less modulation in the 5 to 35 Hz. In each subject, contact configurations chosen for clinically therapeutic stimulation (following data collection and blinded to physiology recordings), were in concordance with the contact pairs showing the largest amplitude of LFP oscillations in the 5–35 Hz range. Although limited to three subjects, these findings provide support for the hypothesis that the sensorimotor territory of the GPi corresponds to the site of maximal power of oscillatory activity in the 5 to 35 Hz and provides the greatest benefit in motor signs during stimulation in the GPi. Variability in oscillatory activity across patients is likely related to Parkinson's disease phenotype as well as small differences in recording location (i.e. lead location), highlighting the importance of lead location for optimizing stimulation efficacy. These data also provide compelling evidence for the use of LFP activity for the development of predictive stimulation models that may optimize patient benefits while reducing clinic time needed for programming.

Response: Commentary: Using Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms.

Response: Commentary: Using Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms.

High resolution transcranial acoustoelectric imaging of current densities from a directional deep brain stimulator

Objective. New innovations in deep brain stimulation (DBS) enable directional current steering—allowing more precise electrical stimulation of the targeted brain structures for Parkinson’s disease, essential tremor and other neurological disorders. While intra-operative navigation through MRI or CT approaches millimeter accuracy for placing the DBS leads, no existing modality provides feedback of the currents as they spread from the contacts through the brain tissue. In this study, we investigate transcranial acoustoelectric imaging (tAEI) as a new modality to non-invasively image and characterize current produced from a directional DBS lead. tAEI uses ultrasound (US) to modulate tissue resistivity to generate detectable voltage signals proportional to the local currents. Approach. An 8-channel directional DBS lead (Infinity 6172ANS, Abbott Inc) was inserted inside three adult human skulls submerged in 0.9% NaCl. A 2.5 MHz linear array delivered US pulses through the transtemporal window and focused near the contacts on the lead, while a custom amplifier and acquisition system recorded the acoustoelectric (AE) interaction used to generate images. Main results. tAEI detected monopolar current with stimulation pulses as short as 100 µs with an SNR ranging from 10–27 dB when using safe US pressure (mechanical indices <0.78) and injected current of ~2 mA peak amplitude. Adjacent contacts were discernable along the length and within each ring of the lead with a mean radial separation between contacts of 2.10 and 1.34 mm, respectively. Significance. These results demonstrate the feasibility of tAEI for high resolution mapping of directional DBS currents using clinically-relevant stimulation parameters. This new modality may improve the accuracy for placing the DBS leads, guide calibration and programming, and monitor long-term performance of DBS for treatment of Parkinson’s disease.

Effects of Directional Subthalamic Deep Brain Stimulation on Gait and Balance in Parkinson's Disease Patients

Effects of Directional Subthalamic Deep Brain Stimulation on Gait and Balance in Parkinson's Disease Patients

Structure-function relationship of the posterior subthalamic area with directional deep brain stimulation for essential tremor

Deep Brain Stimulation of the posterior subthalamic area is an emergent target for the treatment of Essential Tremor. Due to the heterogeneous and complex anatomy of the posterior subthalamic area, it remains unclear which specific structures mediate tremor suppression and different side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate the different clinical effects observed during directional deep brain stimulation of that area.We analysed a consecutive series of 12 essential tremor patients. Imaging analysis and systematic clinical testing performed 4–6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual activation volumes and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects.Stimulation of the dentato-rubro-thalamic tract and the zona incerta was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus. Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts. The best directional contacts did not provide significantly larger therapeutic windows than omnidirectional stimulation at the same level.Deep brain stimulation of the posterior subthalamic area effectively suppresses all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the dentato-rubro-thalamic tract and the zona incerta. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated modelling of activation volumes taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.

The μDBS: Multiresolution, Directional Deep Brain Stimulation for Improved Targeting of Small Diameter Fibers.

Directional deep brain stimulation (DBS) leads have recently been approved and used in patients, and growing evidence suggests that directional contacts can increase the therapeutic window by redirecting stimulation to the target region while avoiding side-effect-inducing regions. We outline the design, fabrication, and testing of a novel directional DBS lead, the μDBS, which utilizes microscale contacts to increase the spatial resolution of stimulation steering and improve the selectivity in targeting small diameter fibers. We outline the steps of fabrication of the μDBS, from an integrated circuit design to post-processing and validation testing. We tested the onboard digital circuitry for programming fidelity, characterized impedance for a variety of electrode sizes, and demonstrated functionality in a saline bath. In a computational experiment, we determined that reduced electrode sizes focus the stimulation effect on small, nearby fibers. Smaller electrode sizes allow for a relative decrease in small-diameter axon thresholds compared to thresholds of large-diameter fibers, demonstrating a focusing of the stimulation effect within small, and possibly therapeutic, fibers. This principle of selectivity could be useful in further widening the window of therapy. The μDBS offers a unique, multiresolution design in which any combination of microscale contacts can be used together to function as electrodes of various shapes and sizes. Multiscale electrodes could be useful in selective neural targeting for established neurological targets and in exploring novel treatment targets for new neurological indications.

Commentary: Using Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms.

Commentary: Using Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms.

Directional DBS leads show large deviations from their intended implantation orientation

ObjectiveLead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort. MethodsThe Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analyzed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared. ResultsDeviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42% of the leads and deviations of more than 60° in about 11% of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used. DiscussionOur results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.

Determining the Rotational Orientation of Directional Deep Brain Stimulation Leads Employing Flat-Panel Computed Tomography.

Directional deep brain stimulation (DBS) constitutes an emerging technology that allows selective stimulation of target structures via partitioned electrode contacts. In order to effectively perform target-tailored stimulation, knowledge of the rotational orientation of the segmented leads is imperative. To develop a universally applicable and reliable method for determination of lead orientation angles in DBS using flat-panel computed tomography (fpCT). A binary template of directional leads DB-2202-30 (Boston Scientific, Natick, Massachusetts) and 6170 (Abbott, Plano, Texas) was imported into the 2-dimensional raw data set of a conventional fpCT scan. The template was aligned with and manually rotated around the predetermined lead trajectory. The overall orientation of the segmented lead can be deduced by transferring position and orientation of the lead orientation marker into the 3-dimensional volume. Accuracy of the method was investigated by two raters in a phantom study. Accuracy were 5.4°±4.1° (range: 0.4°-11.9°) for rater 1 and 5.2°±3.0° (range: 0.3°-10.2°) for rater 2, when investigating DB-2202-30. For 6170 observed deviations were 2.5°±1.7° (range: 0.2°-5.2°) and 4.3°±3.6° (range: 0.2°-11.2°) for raters 1 and 2, respectively. fpCT imaging constitutes a precise and accurate means to determine the rotational orientation of directional leads. The approach is universally transferable to different electrode designs as the template can easily be adjusted to the electrodes' specific measures. The approach is independent from polar implantation angles owing to fpCT- and methodological features.

Proceedings #50: Directional Deep Brain Stimulation Lead Placement in A Patient with Severe Obsessive-Compulsive Disorder

Proceedings #50: Directional Deep Brain Stimulation Lead Placement in A Patient with Severe Obsessive-Compulsive Disorder

DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging

Background: Directional deep brain stimulation (DBS) allows steering the stimulation in an axial direction which offers greater flexibility in programming. However, accurate anatomical visualization of the lead orientation is required for interpreting the observed stimulation effects and to guide programming. Objectives: In this study we aimed to develop and test an accurate and robust algorithm for determining the orientation of segmented electrodes based on standard postoperative CT imaging used in DBS. Methods: Orientation angles of directional leads (Cartesia^TM; Boston Scientific, Marlborough, MA, USA) were determined using CT imaging. Therefore, a sequential algorithm was developed that quantitatively compares the similarity of the observed CT artifacts with calculated artifact patterns based on the lead’s orientation marker and a geometric model of the segmented electrodes. Measurements of seven ground truth phantoms and three leads with 60 different configurations of lead implantation and orientation angles were analyzed for validation. Results: The accuracy of the determined electrode orientation angles was –0.6 ± 1.5° (range: –5.4 to 4.2°). This accuracy proved to be sufficiently high to resolve even subtle differences between individual leads. Conclusions: The presented algorithm is user independent and provides highly accurate results for the orientation of the segmented electrodes for all angular constellations that typically occur in clinical cases.

Multi-objective particle swarm optimization for postoperative deep brain stimulation targeting of subthalamic nucleus pathways

Objective. The effectiveness of deep brain stimulation (DBS) therapy strongly depends on precise surgical targeting of intracranial leads and on clinical optimization of stimulation settings. Recent advances in surgical targeting, multi-electrode designs, and multi-channel independent current-controlled stimulation are poised to enable finer control in modulating pathways within the brain. However, the large stimulation parameter space enabled by these technologies also poses significant challenges for efficiently identifying the most therapeutic DBS setting for a given patient. Here, we present a computational approach for programming directional DBS leads that is based on a non-convex optimization framework for neural pathway targeting. Approach. The algorithm integrates patient-specific pre-operative 7 T MR imaging, post-operative CT scans, and multi-objective particle swarm optimization (MOPSO) methods using dominance based-criteria and incorporating multiple neural pathways simultaneously. The algorithm was evaluated on eight patient-specific models of subthalamic nucleus (STN) DBS to identify electrode configurations and stimulation amplitudes to optimally activate or avoid six clinically relevant pathways: motor territory of STN, non-motor territory of STN, internal capsule, superior cerebellar peduncle, thalamic fasciculus, and hyperdirect pathway. Main results. Across the patient-specific models, single-electrode stimulation showed significant correlations across modeled pathways, particularly for motor and non-motor STN efferents. The MOPSO approach was able to identify multi-electrode configurations that achieved improved targeting of motor STN efferents and hyperdirect pathway afferents than that achieved by any single-electrode monopolar setting at equivalent power levels. Significance. These results suggest that pathway targeting with patient-specific model-based optimization algorithms can efficiently identify non-trivial electrode configurations for enhancing activation of clinically relevant pathways. However, the results also indicate that inter-pathway correlations can limit selectivity for certain pathways even with directional DBS leads.

Directional Deep Brain Stimulation.

Over the last years, deep brain stimulation has seen many technological innovations. New electrode designs allowing to direct the current flow not only in the vertical but also in the horizontal plane are the most recent. We summarize the concept of "directional deep brain stimulation" with its opportunities and challenges and the available study data and discuss the use of imaging techniques to assist programming deep brain stimulation devices.

High-resolution local field potentials measured with deep brain stimulation arrays

Objective. Local field potential (LFP) recordings along a deep brain stimulation (DBS) lead can provide useful feedback for titrating DBS therapy. However, conventional DBS leads with four cylindrical macroelectrodes likely undersample the spatial distribution of sinks and sources in a given brain region. In this study, we investigated the spectral power and spatial feature sizes of LFP activity in non-human primate subthalamic nucleus and globus pallidus using chronically implanted 32-channel directional DBS arrays. Approach. Subthalamic nucleus and globus pallidus LFP signals were recorded from directional DBS arrays in the resting state and during a reach-and-retrieval task in two non-human primates in naïve and parkinsonian conditions. LFP recordings were compared amongst bipolar pairs of electrodes using individual and grouped electrode configurations, with the latter mimicking the cylindrical macroelectrode configurations used in current clinical LFP recordings. Main results. Recordings from these DBS arrays showed that (1) beta oscillations have spatial ‘fingerprints’ in the subthalamic nucleus and globus pallidus, and (2) that these oscillations were muted when grouping electrode contacts together to create cylindrical macroelectrodes similar in relative dimension to those used clinically. Further, these maps depended on parkinsonian condition and whether the subject was resting or performing a motor task. Significance. Development of future closed-loop DBS therapies that rely on LFP feedback will benefit from implanting DBS arrays with electrode sizes and spacings that are more consistent with the dimensions of oscillatory sinks and sources within the brain.

DIRECT DBS: A Prospective, Multi-center Clinical Study with Blinding for a Directional Deep Brain Stimulation (DBS) Lead (P4.068)

DIRECT DBS: A Prospective, Multi-center Clinical Study with Blinding for a Directional Deep Brain Stimulation (DBS) Lead (P4.068)