Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Abstract Objective : The goal of this project was to develop a quantitative understanding of the volume of axonal tissue directly activated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Methods : The 3-dimensionally inhomogeneous and anisotropic tissue medium surrounding DBS electrodes complicates our understanding of the electric field and tissue response generated by the stimulation. We developed finite element computer models to address the effects of DBS in a homogeneous isotropic medium, and a medium with tissue conductivity properties derived from human diffusion tensor magnetic resonance data. The second difference of the potential distribution generated in the tissue medium was used as a predictor of the volume of tissue supra-threshold for axonal activation. Results : The model predicts that clinically effective stimulation parameters (−3 V; 0.1 ms; 150 Hz) result in activation of large diameter (5.7 μm) myelinated axons over a volume that spreads outside the borders of the STN. The shape of the activation volume was dependent on the strong dorsal-ventral anisotropy of the internal capsule, and the moderate anterior-posterior anisotropy of the region around zona incerta. Conclusions : Small deviations (∼1 mm) in the electrode position within STN can substantially alter the shape of the activation volume as well as its spread to neighboring structures. Significance : STN DBS represents an effective treatment for medically refractory movement disorders such as Parkinson's disease. However, stimulation induced side effects such as tetanic muscle contraction, speech disturbance and ocular deviation are not uncommon. Quantitative characterization of the spread of stimulation will aid in the development of techniques to maximize the efficacy of DBS. <s> BIB001 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> OBJECT ::: Adjusting electrical parameters used in deep brain stimulation (DBS) for dystonia remains time consuming and is currently based on clinical observation alone. The goal of this study was to visualize electrical parameters around the electrode, to correlate these parameters with the anatomy of the globus pallidus internus (GPI), and to study the relationship between the volume of stimulated tissue and the electrical parameter settings. ::: ::: ::: METHODS ::: The authors developed a computer-assisted methodological model for visualizing electrical parameters (the isopotential and the isoelectric field magnitude), with reference to the stereotactic target, for different stimulation settings (monopolar and bipolar) applied during DBS. Electrical field values were correlated with the anatomy of the GPI, which was determined by performing stereotactic magnetic resonance imaging in one reference patient. By using this method it is possible to compare potential and electrical field distributions for different stimulation modes. In monopolar and bipolar stimulation, the shape and distribution of the potential and electrical field are different and depend on the stimulation voltage. Distributions visualized for patient-specific parameters can be subsequently correlated with anatomical information. The application of this method to one patient demonstrated that the 0.2-V/ mm isofield line fits best with the lateral GPI borders at the level of the stimulated contacts. ::: ::: ::: CONCLUSIONS ::: The electrical field is a crucial parameter because it is assumed to be responsible for triggering action potentials. Electrical field visualization allows the calculation of the stimulated volume for a given isoline. Its application to an entire series of patients may help determine a threshold for obtaining a therapeutic effect, which is currently unknown, and consequently may aid in optimizing parameter settings in individual patients. <s> BIB002 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> The mismatch between the extensive clinical use of deep brain stimulation (DBS), which is being used to treat an increasing number of neurological disorders, and the lack of understanding of the underlying mechanisms, is confounded by the difficulty of measuring the spread of electric current in the brain in vivo. Here we present a brief review of the recent computational models which simulate the electric current and field distribution in the three-dimensional space, and consequently make estimations of the brain volume being modulated by therapeutic DBS. Such structural modelling work can be categorised into three main approaches: 1) Target specific modelling; 2) Models of instrumentation; 3) Modelling the electrode-brain interface (EBI). Comments are made for each of these approaches with emphasis on our EBI modelling, since the stimulating current must travel across the EBI in order to reach the surrounding brain tissue, and modulate the pathological neural activity. For future modelling work, a combined approach needs to be taken for revealing the underlying mechanisms, and both structural and dynamic models need to be clinically validated to make reliable predictions about the therapeutic effect of DBS in order to assist clinical practice. <s> BIB003 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Deep brain stimulation (DBS) is an increasingly used clinical treatment for various neurological disorders, particularly movement disorders such as Parkinson's disease. However, the mechanism by which these high frequency electrical pulses act on neuronal activity is unclear. Once the stimulating electrode is placed in situ, an electrode–brain interface (EBI) is created. To compensate for the lack of studies on the effects of this generic depth EBI on therapeutic DBS, we constructed a three-dimensional computational model of the EBI using the finite element method, in which the structural details and biophysical properties of the EBI are preserved. Our investigations focus on the peri-electrode space as a significant element of the EBI, and its physiological and pathological modulation, in particular by brain pulsation and giant cell formation. We also consider the difference between the current fields induced by different configurations of the quadripolar electrode contacts. These results quantitatively demonstrated that the peri-electrode space is a significant element of the EBI and its biophysical properties are modulated by brain pulsation and giant cell formation, as well as by the choice of electrode contact configuration. This study leads to a fuller understanding of the EBI and its effects on the crossing electric currents, and will ultimately lead to optimisation of the therapeutic effects of DBS. <s> BIB004 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Abstract Despite the clinical success of deep brain stimulation (DBS) for the treatment of movement disorders, many questions remain about its effects on the nervous system. This study presents a methodology to predict the volume of tissue activated (VTA) by DBS on a patient-specific basis. Our goals were to identify the intersection between the VTA and surrounding anatomical structures and to compare activation of these structures with clinical outcomes. The model system consisted of three fundamental components: (1) a 3D anatomical model of the subcortical nuclei and DBS electrode position in the brain, each derived from magnetic resonance imaging (MRI); (2) a finite element model of the DBS electrode and electric field transmitted to the brain, with tissue conductivity properties derived from diffusion tensor MRI; (3) VTA prediction derived from the response of myelinated axons to the applied electric field, which is a function of the stimulation parameters (contact, impedance, voltage, pulse width, frequency). We used this model system to analyze the effects of subthalamic nucleus (STN) DBS in a patient with Parkinson's disease. Quantitative measurements of bradykinesia, rigidity, and corticospinal tract (CST) motor thresholds were evaluated over a range of stimulation parameter settings. Our model predictions showed good agreement with CST thresholds. Additionally, stimulation through electrode contacts that improved bradykinesia and rigidity generated VTAs that overlapped the zona incerta/fields of Forel (ZI/H2). Application of DBS technology to various neurological disorders has preceded scientific characterization of the volume of tissue directly affected by the stimulation. Synergistic integration of clinical analysis, neuroimaging, neuroanatomy, and neurostimulation modeling provides an opportunity to address wide ranging questions on the factors linked with the therapeutic benefits and side effects of DBS. <s> BIB005 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS. <s> BIB006 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is an established surgical technique for the treatment of movement disorders. The objective of this study was to propose a computational stereotactic model of the electrical distribution around the electrode within the targeted GPi in order to optimize parameter adjustment in clinical practice. The outline of the GPi can be defined precisely by using stereotactic magnetic resonance imaging (MRI) and from this it is possible to model its three-dimensional structure. The electrode and the distribution of the patient-specific parameters can then be co-registered with the GPi volume. By using this methodology, it is possible to visualize and measure the relationship between the electrical distribution of patient-specific parameters and the morphology of the GPi. The model could be applied in clinical practice to help determine the threshold for achieving a therapeutic effect and consequently may aid in optimizing parameter settings for individual patients. <s> BIB007 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Objective: Despite the clinical success of deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD), little is known about the electrical spread of the stimulation. The primary goal of this study was to integrate neuroimaging, neurophysiology and neurostimulation data sets from 10 patients with PD, unilaterally implanted with subthalamic nucleus (STN) DBS electrodes, to identify the theoretical volume of tissue activated (VTA) by clinically defined therapeutic stimulation parameters. Methods: Each patient specific model was created with a series of five steps: (1) definition of the neurosurgical stereotactic coordinate system within the context of preoperative imaging data; (2) entry of intraoperative microelectrode recording locations from neurophysiologically defined thalamic, subthalamic and substantia nigra neurons into the context of the imaging data; (3) fitting a three dimensional brain atlas to the neuroanatomy and neurophysiology of the patient; (4) positioning the DBS electrode in the documented stereotactic location, verified by postoperative imaging data; and (5) calculation of the VTA using a diffusion tensor based finite element neurostimulation model. Results: The patient specific models show that therapeutic benefit was achieved with direct stimulation of a wide range of anatomical structures in the subthalamic region. Interestingly, of the five patients exhibiting a greater than 40% improvement in their Unified PD Rating Scale (UPDRS), all but one had the majority of their VTA outside the atlas defined borders of the STN. Furthermore, of the five patients with less than 40% UPDRS improvement, all but one had the majority of their VTA inside the STN. Conclusions: Our results are consistent with previous studies suggesting that therapeutic benefit is associated with electrode contacts near the dorsal border of the STN, and provide quantitative estimates of the electrical spread of the stimulation in a clinically relevant context. <s> BIB008 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Background/Aims: Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson’s disease. The aim of this study was to investigate the anat <s> BIB009 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Patient-specific models and simulations of the DBS electric field <s> Abstract Deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease involves implantation of a lead with four small contacts usually within the subthalamic nucleus (STN) or globus pallidus internus (GPi). While generally safe from a cognitive standpoint, STN DBS has been commonly associated with a decrease in the speeded production of words, a skill referred to as verbal fluency. Virtually all studies comparing presurgical to postsurgical verbal fluency performance have detected a decrease with DBS. The decline may be attributable in part to the surgical procedures, yet the relative contributions of stimulation effects are not known. In the present study, we used patient-specific DBS computer models to investigate the effects of stimulation on verbal fluency performance. Specifically, we investigated relationships of the volume and locus of activated STN tissue to verbal fluency outcome. Stimulation of different electrode contacts within the STN did not affect total verbal fluency scores. However, models of activation revealed subtle relationships between the locus and volume of activated tissue and verbal fluency performance. At ventral contacts, more tissue activation inside the STN was associated with decreased letter fluency performance. At optimal contacts, more tissue activation within the STN was associated with improved letter fluency performance. These findings suggest subtle effects of stimulation on verbal fluency performance, consistent with the functional nonmotor subregions/somatotopy of the STN. <s> BIB010
The finite element method (FEM) has been used in order to develop computer models of DBS electrodes and to create simulations of the electric field surrounding DBS electrodes  BIB002 BIB001 BIB003 . The equation for steady currents is used in order to calculate the electric potential distribution in the vicinity of the electrode. The first generation of DBS models were used to visualise the electric field for different stimulation settings (monopolar and bipolar) and with reference to the pre-selected stereotactic target area and anatomy, e.g. the GPi BIB002 and the STN BIB001 . Other studies focused on the influence from tissue type in the vicinity of the stimulation area, e.g. cerebrospinal filled cysts  or the electrode-brain interface BIB004 . McIntyre et al. BIB001 also used FEM simulations together with an axon model in order to study the axonal tissue around the STN directly activated by DBS. The second generation of modelling techniques is patientand treatment-specific, i.e. based on individual input data and electrode settings BIB006 BIB005 BIB007 . Butson et al. BIB005 were, by using DTI as input for handling potential anisotropic tissue, able to study in detail the electric potential when stimulating in the STN. The technique has been further developed and used in patients in order to identify and visualise the theoretical volume of activated tissue around the STN BIB008 BIB010 . The activated volume around the GPi has been studied and visualised with a computational stereotactic model by Vasques et al. BIB007 . An approach based on the individual patient's preoperative MR batch of images, in order to classify the electrical conductivity for different tissue types, has been developed by Å ström et al. BIB006 . With the help of treatment-specific positioning of the DBS electrode in relation to the postoperative MR images, the method allows for investigations of the relative electric field changes in relation to anatomy and DBS settings (Fig. 3) . The latter technique has been used for evaluation of speech intelligibility and movement in patients with Parkinson's disease where DBS electrodes were implanted in the STN BIB009 .