Deep brain stimulation (DBS) is an effective surgical treatment for medication-refractory hypokinetic and hyperkinetic movement disorders, and it is being explored for a variety of other neurological and psychiatric diseases Deep brain stimulation has been Food and Drug Administration-approved for essential tremor and Parkinson disease and has a humanitarian device exemption for dystonia and obsessive-compulsive disorder Neurostimulation is the fruit of decades of both technical and scientific advances in the field of basic neuroscience and functional neurosurgery Despite the clinical success of DBS, the therapeutic mechanism of DBS remains under debate Our objective is to provide a comprehensive review of DBS focusing on movement disorders, including the historical evolution of the technique, applications and outcomes with an overview of the most pertinent literature, current views on mechanisms of stimulation, and description of hardware and programming techniques We conclude with a discussion of future developments in neurostimulation

https://jamanetwork.com/journals/jamaneurology/articlepdf/1391074/nnr120008_163_171.pdf

History, Applications, and Mechanisms of Deep Brain Stimulation

Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS.

Mechanisms of deep brain stimulation.

Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinson's disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in omnidirectional mode, compared with 4.2 mm(3) when only one electrode was used. Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the subthalamic nucleus as well as in the nucleus ventralis intermedius of the thalamus significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.

Directional deep brain stimulation: an intraoperative double-blind pilot study.

A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm2. With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro.

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A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation

Spatial steering of deep brain stimulation volumes using a novel lead design

A method and control system for determining and applying stimulation settings for a brain stimulation probe (10, 12) is provided. The brain stimulation probe (10, 12) comprises a plurality of stimulation electrodes (11). The method comprises for multiple stimulation electrodes (11) of the plurality of stimulation electrodes (11): applying a test current and determining a corresponding patient response, determining a volume of influence based (32, 52, 71, 91) on the test current and a position of the stimulation electrode (11), combining the volume of influence (32, 52, 71, 91) and the corresponding patient response with generalized anatomic knowledge of stimulation induced behavior for associating the volume of influence (32, 52, 71, 91) to an anatomic structure (33, 43, 53), and determining an intersection (41, 51) of the volume of influence (32, 52, 71, 91) and the associated anatomic structure (33, 43, 53). Then, based on the determined intersections (41, 51) an optimal stimulation volume and corresponding stimulation settings for the brain stimulation probe (10, 12) are determined.

Method and System for Determining Settings for Deep Brain Stimulation

Deep brain stimulation (DBS) therapy relies on electrical stimulation of neuronal elements in small brain targets. However, the lack of fine spatial control over field distributions in current systems implies that stimulation easily spreads into adjacent structures that may induce adverse side-effects. This study investigates DBS field steering using a novel DBS lead design carrying a high-resolution electrode array. We apply computational models to simulate voltage distributions and DBS activation volumes in order to theoretically assess the potential of field steering in DBS. Our computational analysis demonstrates that the DBS-array is capable of accurately displacing activation volumes with sub-millimeter precision. Our findings demonstrate that future systems for DBS therapy may provide for more accurate target coverage than currently available systems achieve.

Steering deep brain stimulation fields using a high resolution electrode array

A method and system are provided for determining a relation between stimulation settings for a brain stimulation probe and a corresponding V-field. The brain stimulation probe comprises multiple stimulation electrodes. The V-field is an electrical field in brain tissue surrounding the stimulation electrodes. The method comprises sequentially applying a test current to n stimulation electrodes, n being a number between 2 and the number of stimulation electrodes of the brain stimulation probe, for each test current at one of the n stimulation electrodes, measuring a resulting excitation voltage at m stimulation electrodes, m being a number between 2 and the number of stimulation electrodes of the brain stimulation probe, from the stimulation settings and the measured excitation voltages, deriving a coupling matrix, an element in the coupling matrix reflecting an amount of electrical impedance between two of the stimulation electrodes, and using the coupling matrix for determining the relation between the stimulation settings and the corresponding V-field.

System for determining settings for deep brain stimulation

Deep brain stimulation (DBS) is a promising treatment for various brain disorders but the uncontrolled spread of stimulation outside target regions may induce side effects. With existing DBS leads, such side effects can be countered only by lowering the stimulus intensity, thus trading off the potential therapeutic benefit. New generations of leads are being developed that provide more and smaller electrodes. Using such DBS electrodes could allow the stimulation to be “steered” selectively to only target areas, which would prevent the occurrence of stimulation side effects while maintaining the optimal therapeutic benefit. We discuss various novel DBS lead designs that are currently in development stages. Using computational modeling, we theoretically address the expected improvements provided by these electrodes. To quantify the benefit of steering, we introduce two parameters: target coverage, i.e., the fraction of the target that receives stimulation, and target selectivity, i.e., the fraction of stimulation that does not leak outside the target, where it could induce side effects. We demonstrate that lead designs providing enhanced electrode resolution in both axial and circumferential directions may enable superior target coverage and target selectivity. Such high-resolution leads may provide clinicians with an additional degree of freedom to optimize neurostimulation therapy.

Emil Toader

Papers

Spatial steering of deep brain stimulation volumes using a novel lead design

Method and System for Determining Settings for Deep Brain Stimulation

Steering deep brain stimulation fields using a high resolution electrode array

System for determining settings for deep brain stimulation

Next-Generation Electrodes for Steering Brain Stimulation