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Sample records for stimulation dbs electrodes

  1. Probabilistic conversion of neurosurgical DBS electrode coordinates into MNI space.

    PubMed

    Horn, Andreas; Kühn, Andrea A; Merkl, Angela; Shih, Ludy; Alterman, Ron; Fox, Michael

    2017-02-03

    In neurosurgical literature, findings such as deep brain stimulation (DBS) electrode positions are conventionally reported in relation to the anterior and posterior commissures of the individual patient (AC/PC coordinates). However, the neuroimaging literature including neuroanatomical atlases, activation patterns, and brain connectivity maps has converged on a different population-based standard (MNI coordinates). Ideally, one could relate these two literatures by directly transforming MRIs from neurosurgical patients into MNI space. However obtaining these patient MRIs can prove difficult or impossible, especially for older studies or those with hundreds of patients. Here, we introduce a methodology for mapping an AC/PC coordinate (such as a DBS electrode position) to MNI space without the need for MRI scans from the patients themselves. We validate our approach using a cohort of DBS patients in which MRIs are available, and test whether several variations on our approach provide added benefit. We then use our approach to convert previously reported DBS electrode coordinates from eight different neurological and psychiatric diseases into MNI space. Finally, we demonstrate the value of such a conversion using the DBS target for essential tremor as an example, relating the site of the active DBS contact to different MNI atlases as well as anatomical and functional connectomes in MNI space.

  2. Temperature Control at DBS Electrodes using Heat Sink: Experimentally Validated FEM Model of DBS lead Architecture

    PubMed Central

    Elwassif, Maged M.; Datta, Abhishek; Rahman, Asif; Bikson, Marom

    2012-01-01

    There is a growing interest in the use of Deep Brain Stimulation for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. MRI) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols, and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: 1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); 2) does not interfere with device efficacy; and 3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure. PMID:22764359

  3. Posteroventrolateral pallidotomy through implanted DBS electrodes monitored by recording local field potentials.

    PubMed

    Franzini, Angelo; Cordella, Roberto; Penner, Federica; Rosa, Manuela; Messina, Giuseppe; Rizzi, Michele; Nardocci, Nardo; Priori, Alberto

    2015-01-01

    This paper describes the use of globus pallidus internus (Gpi) local field potentials recorded through pre-implanted deep brain stimulation (DBS) electrodes on a patient affected by generalized dystonia. The recordings were made both before and after radiofrequency-induced posteroventrolateral bilateral stereotactic pallidotomy. LFP patterns and macroelectrode impedances were modified after the pallidotomy, along with the improvement of dystonic symptoms. After implantation, the DBS electrodes were used for subsequent bedside pallidotomies that were required by the evolution and/or persistence of symptoms. In our hands, LFPs were safe and effective in monitoring pallidotomy performed through DBS electrodes.

  4. DBSproc: An open source process for DBS electrode localization and tractographic analysis.

    PubMed

    Lauro, Peter M; Vanegas-Arroyave, Nora; Huang, Ling; Taylor, Paul A; Zaghloul, Kareem A; Lungu, Codrin; Saad, Ziad S; Horovitz, Silvina G

    2016-01-01

    Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders. Although stimulation sites for movement disorders such as Parkinson's disease are established, the therapeutic mechanisms of DBS remain controversial. Recent research suggests that specific white-matter tract and circuit activation mediates symptom relief. To investigate these questions, we have developed a patient-specific open-source software pipeline called 'DBSproc' for (1) localizing DBS electrodes and contacts from postoperative CT images, (2) processing structural and diffusion MRI data, (3) registering all images to a common space, (4) estimating DBS activation volume from patient-specific voltage and impedance, and (5) understanding the DBS contact-brain connectivity through probabilistic tractography. In this paper, we explain our methodology and provide validation with anatomical and tractographic data. This method can be used to help investigate mechanisms of action of DBS, inform surgical and clinical assessments, and define new therapeutic targets.

  5. Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture.

    PubMed

    Elwassif, Maged M; Datta, Abhishek; Rahman, Asif; Bikson, Marom

    2012-08-01

    There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

  6. Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture

    NASA Astrophysics Data System (ADS)

    Elwassif, Maged M.; Datta, Abhishek; Rahman, Asif; Bikson, Marom

    2012-08-01

    There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

  7. An external portable device for adaptive deep brain stimulation (aDBS) clinical research in advanced Parkinson's Disease.

    PubMed

    Arlotti, Mattia; Rossi, Lorenzo; Rosa, Manuela; Marceglia, Sara; Priori, Alberto

    2016-05-01

    Compared to conventional deep brain stimulation (DBS) for patients with Parkinson's Disease (PD), the newer approach of adaptive DBS (aDBS), regulating stimulation on the basis of the patient's clinical state, promises to achieve better clinical outcomes, avoid adverse-effects and save time for tuning parameters. A remaining challenge before aDBS comes into practical use is to prove its feasibility and its effectiveness in larger groups of patients and in more ecological conditions. We developed an external portable aDBS system prototype designed for clinical testing in freely-moving PD patients with externalized DBS electrodes. From a single-channel bipolar artifact-free recording, it analyses local field potentials (LFPs), during ongoing DBS for tuning stimulation parameters, independent from the specific feedback algorithm implemented. We validated the aDBS system in vitro, by testing both its sensing and closed-loop stimulation capabilities, and then tested it in vivo, focusing on the sensing capabilities. By applying the aDBS system prototype in a patient with PD, we provided evidence that it can track levodopa and DBS-induced LFP spectral power changes among different patient's clinical states. Our system, intended for testing LFP-based feedback strategies for aDBS, should help understanding how and whether aDBS therapy works in PD and indicating future technical and clinical advances.

  8. A critical reflection on the technological development of deep brain stimulation (DBS)

    PubMed Central

    Ineichen, Christian; Glannon, Walter; Temel, Yasin; Baumann, Christian R.; Sürücü, Oguzkan

    2014-01-01

    Since the translational research findings of Benabid and colleagues which partly led to their seminal paper regarding the treatment of mainly tremor-dominant Parkinson patients through thalamic high-frequency-stimulation (HFS) in 1987, we still struggle with identifying a satisfactory mechanistic explanation of the underlying principles of deep brain stimulation (DBS). Furthermore, the technological advance of DBS devices (electrodes and implantable pulse generators, IPG’s) has shown a distinct lack of dynamic progression. In light of this we argue that it is time to leave the paleolithic age and enter hellenistic times: the device-manufacturing industry and the medical community together should put more emphasis on advancing the technology rather than resting on their laurels. PMID:25278864

  9. Rescue pallidotomy for dystonia through implanted deep brain stimulation electrode

    PubMed Central

    Blomstedt, Patric; Taira, Takaomi; Hariz, Marwan

    2016-01-01

    Background: Some patients with deep brain stimulation (DBS), where removal of implants is indicated due to hardware related infections, are not candidates for later re-implantation. In these patients a rescue lesion through the DBS electrode has been suggested as an option. In this case report we present a patient where a pallidotomy was performed using the DBS electrode. Case Description: An elderly woman with bilateral Gpi DBS suffered an infection around the left burr hole involving the DBS electrode. A unilateral lesion was performed through the DBS electrode before it was removed. No side effects were encountered. Burke-Fahn-Marsden (BFM) dystonia movement scale score was 39 before DBS. With DBS before lesioning BFM score was 2.5 points. The replacement of the left sided stimulation with a pallidotomy resulted in only a minor deterioration of the score to 5 points. Conclusions: In the case presented here a small pallidotomy performed with the DBS electrode provided a satisfactory effect on the patient's dystonic symptoms. Thus, rescue lesions through the DBS electrodes, although off-label, might be considered in patients with Gpi DBS for dystonia when indicated. PMID:27990311

  10. SaBer DBS: a fully programmable, rechargeable, bilateral, charge-balanced preclinical microstimulator for long-term neural stimulation

    PubMed Central

    Ewing, Samuel G.; Porr, Bernd; Riddell, John; Winter, Christine; Grace, Anthony A.

    2013-01-01

    To effectively study the mechanisms by which deep brain stimulation (DBS) produces its therapeutic benefit and to evaluate new therapeutic indications, it is vital to administer DBS over an extended period of time in awake, freely behaving animals. To date multiple preclinical stimulators have been designed and described. However, these stimulators have failed to incorporate some of the design criteria necessary to provide a system analogous to those used clinically. Here we define these design criteria and propose an improved and complete preclinical DBS system. This system is fully programmable in frequency, pulse-width and current amplitude, has a rechargeable battery and delivers biphasic, charge-balanced output to two independent electrodes. The system has been optimized for either implantation or for use externally via attachment to rodent jackets. PMID:23305773

  11. In vivo impedance spectroscopy of deep brain stimulation electrodes.

    PubMed

    Lempka, Scott F; Miocinovic, Svjetlana; Johnson, Matthew D; Vitek, Jerrold L; McIntyre, Cameron C

    2009-08-01

    Deep brain stimulation (DBS) represents a powerful clinical technology, but a systematic characterization of the electrical interactions between the electrode and the brain is lacking. The goal of this study was to examine the in vivo changes in the DBS electrode impedance that occur after implantation and during clinically relevant stimulation. Clinical DBS devices typically apply high-frequency voltage-controlled stimulation, and as a result, the injected current is directly regulated by the impedance of the electrode-tissue interface. We monitored the impedance of scaled-down clinical DBS electrodes implanted in the thalamus and subthalamic nucleus of a rhesus macaque using electrode impedance spectroscopy (EIS) measurements ranging from 0.5 Hz to 10 kHz. To further characterize our measurements, equivalent circuit models of the electrode-tissue interface were used to quantify the role of various interface components in producing the observed electrode impedance. Following implantation, the DBS electrode impedance increased and a semicircular arc was observed in the high-frequency range of the EIS measurements, commonly referred to as the tissue component of the impedance. Clinically relevant stimulation produced a rapid decrease in electrode impedance with extensive changes in the tissue component. These post-operative and stimulation-induced changes in impedance could play an important role in the observed functional effects of voltage-controlled DBS and should be considered during clinical stimulation parameter selection and chronic animal research studies.

  12. Betting on DBS: Effects of Subthalamic Nucleus Deep Brain Stimulation on Risk-Taking and Decision-Making in Patients with Parkinson’s Disease

    PubMed Central

    Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C.; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

    2014-01-01

    Objective Concerns persist that deep brain stimulation (DBS) for Parkinson’s disease (PD) increases impulsivity and/or induces excessive reward-seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on three laboratory tasks of risk-taking and decision-making. They are compared to PD patients maintained on medication and normal control subjects. Methods and Results In the Game of Dice Task, a test of “risky” decision-making, PD patients with or without DBS made highest-risk bets more often, and ended up with less money, than normal controls. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an “ambiguous” decision-making task that assessed preference for risk (holding on to one’s briefcase) over a “sure thing” (accepting the banker’s offer). Here, DBS patients were more conservative with stimulation on than off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the two PD groups won less money than healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was “framed” as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than normal subjects, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. Conclusions On “risky” decision-making tasks, DBS patients were more risk-taking than normal, but stimulation may temper this tendency. In contrast, in an “ambiguous risk” situation, DBS patients were more risk-averse (conservative) than normal, and this tendency was greatest with stimulation. PMID:25486385

  13. Modeling deep brain stimulation: point source approximation versus realistic representation of the electrode

    NASA Astrophysics Data System (ADS)

    Zhang, Tianhe C.; Grill, Warren M.

    2010-12-01

    Deep brain stimulation (DBS) has emerged as an effective treatment for movement disorders; however, the fundamental mechanisms by which DBS works are not well understood. Computational models of DBS can provide insights into these fundamental mechanisms and typically require two steps: calculation of the electrical potentials generated by DBS and, subsequently, determination of the effects of the extracellular potentials on neurons. The objective of this study was to assess the validity of using a point source electrode to approximate the DBS electrode when calculating the thresholds and spatial distribution of activation of a surrounding population of model neurons in response to monopolar DBS. Extracellular potentials in a homogenous isotropic volume conductor were calculated using either a point current source or a geometrically accurate finite element model of the Medtronic DBS 3389 lead. These extracellular potentials were coupled to populations of model axons, and thresholds and spatial distributions were determined for different electrode geometries and axon orientations. Median threshold differences between DBS and point source electrodes for individual axons varied between -20.5% and 9.5% across all orientations, monopolar polarities and electrode geometries utilizing the DBS 3389 electrode. Differences in the percentage of axons activated at a given amplitude by the point source electrode and the DBS electrode were between -9.0% and 12.6% across all monopolar configurations tested. The differences in activation between the DBS and point source electrodes occurred primarily in regions close to conductor-insulator interfaces and around the insulating tip of the DBS electrode. The robustness of the point source approximation in modeling several special cases—tissue anisotropy, a long active electrode and bipolar stimulation—was also examined. Under the conditions considered, the point source was shown to be a valid approximation for predicting excitation

  14. Deep brain stimulation (DBS) at the interface of neurology and psychiatry

    PubMed Central

    Williams, Nolan R.; Okun, Michael S.

    2013-01-01

    Deep brain stimulation (DBS) is an emerging interventional therapy for well-screened patients with specific treatment-resistant neuropsychiatric diseases. Some neuropsychiatric conditions, such as Parkinson disease, have available and reasonable guideline and efficacy data, while other conditions, such as major depressive disorder and Tourette syndrome, have more limited, but promising results. This review summarizes both the efficacy and the neuroanatomical targets for DBS in four common neuropsychiatric conditions: Parkinson disease, Tourette syndrome, major depressive disorder, and obsessive-compulsive disorder. Based on emerging new research, we summarize novel approaches to optimization of stimulation for each neuropsychiatric disease and we review the potential positive and negative effects that may be observed following DBS. Finally, we summarize the likely future innovations in the field of electrical neural-network modulation. PMID:24177464

  15. Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia

    PubMed Central

    Mandali, Alekhya; Chakravarthy, V. Srinivasa

    2016-01-01

    Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic

  16. Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia.

    PubMed

    Mandali, Alekhya; Chakravarthy, V Srinivasa

    2016-01-01

    Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic

  17. My 25 Stimulating Years with DBS in Parkinson’s Disease

    PubMed Central

    Hariz, Marwan

    2017-01-01

    The year 2017 marks the 30th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid, Pollak et al. in 1987, initially targeting the motor thalamus to treat tremor, and subsequently targeting the subthalamic nucleus (STN) for treatment of symptoms of advanced Parkinson’s disease (PD). STN DBS is undoubtedly “the most important discovery since levodopa”, as stated by David Marsden in 1994. In 2014, The Lasker– DeBakey Clinical Medical Research Award to “honor two scientists who developed deep brain stimulation of the subthalamic nucleus”, was bestowed upon Benabid and DeLong. STN DBS remains today the main surgical procedure for PD, due to its effectiveness in ameliorating PD symptoms and because it is the only surgical procedure for PD that allows a radical decrease in medication. Future improvements of DBS include the possibility to deliver a “closed-loop”, “on demand” stimulation, as highly preliminary studies suggest that it may improve both axial and appendicular symptoms and reduce side effects such as dysarthria. Even though DBS of the subthalamic nucleus is the main surgical procedure used today for patients with PD, all patients are not suitable for STN DBS; as a functional neurosurgeon performing since more than 25 years various surgical procedures the aim of which is not to save life but to improve the patient’s quality of life, I consider that the surgery should be tailored to the patient’s individual symptoms and needs, and that its safety is paramount. PMID:28282816

  18. Pedunculopontine arousal system physiology - Deep brain stimulation (DBS).

    PubMed

    Garcia-Rill, Edgar; Luster, Brennon; D'Onofrio, Stasia; Mahaffey, Susan; Bisagno, Veronica; Urbano, Francisco J

    2015-11-01

    This review describes the wake/sleep symptoms present in Parkinson׳s disease, and the role of the pedunculopontine nucleus in these symptoms. The physiology of PPN cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for deep brain stimulation in the treatment of gait and postural deficits in Parkinson׳s disease. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from deep brain stimulation for movement disorders.

  19. Pedunculopontine arousal system physiology – Deep brain stimulation (DBS)

    PubMed Central

    Garcia-Rill, Edgar; Luster, Brennon; D’Onofrio, Stasia; Mahaffey, Susan; Bisagno, Veronica; Urbano, Francisco J.

    2015-01-01

    This review describes the wake/sleep symptoms present in Parkinson׳s disease, and the role of the pedunculopontine nucleus in these symptoms. The physiology of PPN cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for deep brain stimulation in the treatment of gait and postural deficits in Parkinson׳s disease. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from deep brain stimulation for movement disorders. PMID:26779322

  20. Automatic target and trajectory identification for deep brain stimulation (DBS) procedures.

    PubMed

    Guo, Ting; Parrent, Andrew G; Peters, Terry M

    2007-01-01

    This paper presents an automatic surgical target and trajectory identification technique for planning deep brain stimulation (DBS) procedures. The probabilistic functional maps, constructed from population-based actual stimulating field information and intra-operative electrophysiological activities, were integrated into a neurosurgical visualization and navigation system to facilitate the surgical planning and guidance. In our preliminary studies, we compared the actual surgical target locations and trajectories established by an experienced stereotactic neurosurgeon with those automatically planned using our probabilistic functional maps on 10 subthalamic nucleus (STN) DBS procedures. The average displacement between the surgical target locations in both groups was 1.82mm with a standard deviation of 0.77mm. The difference between the surgical trajectories was 3.1 degrees and 2.3 degrees in the lateral-to-medial and anterior-to-posterior orientations respectively.

  1. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    PubMed

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  2. Pathological Alterations and Stress Responses near DBS Electrodes after MRI Scans at 7.0T, 3.0T and 1.5T: An In Vivo Comparative Study

    PubMed Central

    Meng, Da-Wei; Li, Shao-Wu; Liu, Huan-Guang; Li, Jun-Ju; Wang, Xiu; Zhang, Xin; Zhang, Jian-Guo

    2014-01-01

    Objective The purpose of this study was to investigate the pathological alterations and the stress responses around deep brain stimulation (DBS) electrodes after magnetic resonance imaging (MRI) scans at 7.0T, 3.0T and 1.5T. Materials and Methods DBS devices were stereotactically implanted into the brains of New Zealand rabbits, targeting the left nucleus ventralis posterior thalami, while on the right side, a puncture passage pointing to the same target was made. MRI scans at 7.0T, 3.0T and 1.5T were performed using transmit/receive head coils. The pathological alterations of the surrounding tissue were evaluated by hematoxylin and eosin staining (H&E staining) and transmission electron microscopy (TEM). The levels of the 70 kDa heat shock protein (HSP-70), Neuronal Nuclei (NeuN) and Caspase-3 were determined by western-blotting and quantitative polymerase chain reaction (QPCR) to assess the stress responses near the DBS electrodes. Results H&E staining and TEM showed that the injury around the DBS electrodes was featured by a central puncture passage with gradually weakened injurious alterations. Comparisons of the injury across the groups manifested similar pathological alterations near the DBS electrodes in each group. Moreover, western-blotting and QPCR assay showed that the level of HSP-70 was not elevated by MRI scans (p>0.05), and the levels of NeuN and Caspase-3 were equal in each group, regardless of the field strengths applied (p>0.05). Conclusions Based on these findings, it is reasonable to conclude that in this study the MRI scans at multiple levels failed to induce additional tissue injury around the DBS electrodes. These preliminary data furthered our understanding of MRI-related DBS heating and encouraged revisions of the current MRI guidelines for patients with DBS devices. PMID:24988329

  3. Carbon nanotube yarns for deep brain stimulation electrode.

    PubMed

    Jiang, Changqing; Li, Luming; Hao, Hongwei

    2011-12-01

    A new form of deep brain stimulation (DBS) electrode was proposed that was made of carbon nanotube yarns (CNTYs). Electrode interface properties were examined using cyclic voltammetry (CV) and electrochemical impedance spectrum (EIS). The CNTY electrode interface exhibited large charge storage capacity (CSC) of 12.3 mC/cm(2) which increased to 98.6 mC/cm(2) after acid treatment, compared with 5.0 mC/cm(2) of Pt-Ir. Impedance spectrum of both untreated and treated CNTY electrodes showed that finite diffusion process occurred at the interface due to their porous structure and charge was delivered through capacitive mechanism. To evaluate stability electrical stimulus was exerted for up to 72 h and CV and EIS results of CNTY electrodes revealed little alteration. Therefore CNTY could make a good electrode material for DBS.

  4. Influences of Interpolation Error, Electrode Geometry, and the Electrode-Tissue Interface on Models of Electric Fields Produced by Deep Brain Stimulation

    PubMed Central

    Howell, Bryan; Naik, Sagar; Grill, Warren M.

    2014-01-01

    Deep brain stimulation (DBS) is an established therapy for movement disorders, but the fundamental mechanisms by which DBS has its effects remain unknown. Computational models can provide insights into the mechanisms of DBS, but to be useful, the models must have sufficient detail to predict accurately the electric fields produced by DBS. We used a finite element method model of the Medtronic 3387 electrode array, coupled to cable models of myelinated axons, to quantify how interpolation errors, electrode geometry, and the electrode-tissue interface affect calculation of electrical potentials and stimulation thresholds for populations of model nerve fibers. Convergence of the potentials was not a sufficient criterion for ensuring the same degree of accuracy in subsequent determination of stimulation thresholds, because the accuracy of the stimulation thresholds depended on the order of the elements. Simplifying the 3387 electrode array by ignoring the inactive contacts and extending the terminated end of the shaft had position dependent effects on the potentials and excitation thresholds, and these simplifications may impact correlations between DBS parameters and clinical outcomes. When the current density in the bulk tissue is uniform, the effect of the electrode-tissue interface impedance could be approximated by filtering the potentials calculated with a static lumped electrical equivalent circuit. Further, for typical DBS parameters during voltage-regulated stimulation, it was valid to approximate the electrode as an ideal polarized electrode with a nonlinear capacitance. Validation of these computational considerations enables accurate modeling of the electric field produced by DBS. PMID:24448594

  5. Role of electrode design on the volume of tissue activated during deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Butson, Christopher R.; McIntyre, Cameron C.

    2006-03-01

    Deep brain stimulation (DBS) is an established clinical treatment for a range of neurological disorders. Depending on the disease state of the patient, different anatomical structures such as the ventral intermediate nucleus of the thalamus (VIM), the subthalamic nucleus or the globus pallidus are targeted for stimulation. However, the same electrode design is currently used in nearly all DBS applications, even though substantial morphological and anatomical differences exist between the various target nuclei. The fundamental goal of this study was to develop a theoretical understanding of the impact of changes in the DBS electrode contact geometry on the volume of tissue activated (VTA) during stimulation. Finite element models of the electrodes and surrounding medium were coupled to cable models of myelinated axons to predict the VTA as a function of stimulation parameter settings and electrode design. Clinical DBS electrodes have cylindrical contacts 1.27 mm in diameter (d) and 1.5 mm in height (h). Our results show that changes in contact height and diameter can substantially modulate the size and shape of the VTA, even when contact surface area is preserved. Electrode designs with a low aspect ratio (d/h) maximize the VTA by providing greater spread of the stimulation parallel to the electrode shaft without sacrificing lateral spread. The results of this study provide the foundation necessary to customize electrode design and VTA shape for specific anatomical targets, and an example is presented for the VIM. A range of opportunities exist to engineer DBS systems to maximize stimulation of the target area while minimizing stimulation of non-target areas. Therefore, it may be possible to improve therapeutic benefit and minimize side effects from DBS with the design of target-specific electrodes.

  6. Role of electrode design on the volume of tissue activated during deep brain stimulation.

    PubMed

    Butson, Christopher R; McIntyre, Cameron C

    2006-03-01

    Deep brain stimulation (DBS) is an established clinical treatment for a range of neurological disorders. Depending on the disease state of the patient, different anatomical structures such as the ventral intermediate nucleus of the thalamus (VIM), the subthalamic nucleus or the globus pallidus are targeted for stimulation. However, the same electrode design is currently used in nearly all DBS applications, even though substantial morphological and anatomical differences exist between the various target nuclei. The fundamental goal of this study was to develop a theoretical understanding of the impact of changes in the DBS electrode contact geometry on the volume of tissue activated (VTA) during stimulation. Finite element models of the electrodes and surrounding medium were coupled to cable models of myelinated axons to predict the VTA as a function of stimulation parameter settings and electrode design. Clinical DBS electrodes have cylindrical contacts 1.27 mm in diameter (d) and 1.5 mm in height (h). Our results show that changes in contact height and diameter can substantially modulate the size and shape of the VTA, even when contact surface area is preserved. Electrode designs with a low aspect ratio (d/h) maximize the VTA by providing greater spread of the stimulation parallel to the electrode shaft without sacrificing lateral spread. The results of this study provide the foundation necessary to customize electrode design and VTA shape for specific anatomical targets, and an example is presented for the VIM. A range of opportunities exist to engineer DBS systems to maximize stimulation of the target area while minimizing stimulation of non-target areas. Therefore, it may be possible to improve therapeutic benefit and minimize side effects from DBS with the design of target-specific electrodes.

  7. Theoretical Optimization of Stimulation Strategies for a Directionally Segmented Deep Brain Stimulation Electrode Array

    PubMed Central

    Xiao, YiZi; Peña, Edgar; Johnson, Matthew D.

    2016-01-01

    Goal Programming deep brain stimulation (DBS) systems currently involves a clinician manually sweeping through a range of stimulus parameter settings to identify the setting that delivers the most robust therapy for a patient. With the advent of DBS arrays with a higher number and density of electrodes, this trial and error process becomes unmanageable in a clinical setting. This study developed a computationally efficient, model-based algorithm to estimate an electrode configuration that will most strongly activate tissue within a volume of interest. Methods The cerebellar-receiving area of motor thalamus, the target for treating essential tremor with DBS, was rendered from imaging data and discretized into grid points aligned in approximate afferent and efferent axonal pathway orientations. A finite-element model (FEM) was constructed to simulate the volumetric tissue voltage during DBS. We leveraged the principle of voltage superposition to formulate a convex optimization-based approach to maximize activating function (AF) values at each grid point (via three different criteria), hence increasing the overall probability of action potential initiation and neuronal entrainment within the target volume. Results For both efferent and afferent pathways, this approach achieved global optima within several seconds. The optimal electrode configuration and resulting AF values differed across each optimization criteria and between axonal orientations. Conclusion This approach only required a set of FEM simulations equal to the number of DBS array electrodes, and could readily accommodate anisotropic-inhomogeneous tissue conductances or other axonal orientations. Significance The algorithm provides an efficient, flexible determination of optimal electrode configurations for programming DBS arrays. PMID:26208259

  8. Standard Guidelines for Publication of Deep Brain Stimulation Studies in Parkinson’s Disease (Guide4DBS-PD)

    PubMed Central

    Vitek, Jerrold L.; Lyons, Kelly E.; Bakay, Roy; Benabid, Alim-Louis; Deuschl, Guenther; Hallett, Mark; Kurlan, Roger; Pancrazio, Joseph J.; Rezai, Ali; Walter, Benjamin L.; Lang, Anthony E.

    2015-01-01

    While the use of deep brain stimulation (DBS) for the treatment of neurological disorders has risen substantially over the last decade, it is often difficult to compare the results from different studies due to the lack of consistent reporting of key study parameters. We present guidelines to standardize the reporting of clinical studies of DBS for Parkinson’s disease (PD). These guidelines provide a minimal set of required data elements to facilitate the interpretation and comparison of results across published clinical studies. The guidelines, summarized in the format of a checklist, may also have utility in the planning of clinical studies of DBS for PD as well as other neurological and psychiatric disorders. PMID:20544809

  9. Electrode array for neural stimulation

    DOEpatents

    Wessendorf, Kurt O.; Okandan, Murat; Stein, David J.; Yang, Pin; Cesarano, III, Joseph; Dellinger, Jennifer

    2011-08-16

    An electrode array for neural stimulation is disclosed which has particular applications for use in a retinal prosthesis. The electrode array can be formed as a hermetically-sealed two-part ceramic package which includes an electronic circuit such as a demultiplexer circuit encapsulated therein. A relatively large number (up to 1000 or more) of individually-addressable electrodes are provided on a curved surface of a ceramic base portion the electrode array, while a much smaller number of electrical connections are provided on a ceramic lid of the electrode array. The base and lid can be attached using a metal-to-metal seal formed by laser brazing. Electrical connections to the electrode array can be provided by a flexible ribbon cable which can also be used to secure the electrode array in place.

  10. Evaluation of high-perimeter electrode designs for deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Howell, Bryan; Grill, Warren M.

    2014-08-01

    Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, complications including infections and mis-programing following surgical replacement of the battery-powered implantable pulse generator adversely impact the safety profile of this therapy. We sought to decrease power consumption and extend battery life by modifying the electrode geometry to increase stimulation efficiency. The specific goal of this study was to determine whether electrode contact perimeter or area had a greater effect on increasing stimulation efficiency. Approach. Finite-element method (FEM) models of eight prototype electrode designs were used to calculate the electrode access resistance, and the FEM models were coupled with cable models of passing axons to quantify stimulation efficiency. We also measured in vitro the electrical properties of the prototype electrode designs and measured in vivo the stimulation efficiency following acute implantation in anesthetized cats. Main results. Area had a greater effect than perimeter on altering the electrode access resistance; electrode (access or dynamic) resistance alone did not predict stimulation efficiency because efficiency was dependent on the shape of the potential distribution in the tissue; and, quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. Significance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes.

  11. Neural stimulation and recording electrodes.

    PubMed

    Cogan, Stuart F

    2008-01-01

    Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.

  12. A target-specific electrode and lead design for internal globus pallidus deep brain stimulation.

    PubMed

    Vasques, Xavier; Cif, Laura; Mennessier, Gérard; Coubes, Philippe

    2010-01-01

    In nearly all deep brain stimulation (DBS) applications, the same quadripolar electrode design is used for different anatomical targets even if shape and volume differences exist between nuclei. Taking into account the electrode location within the internal globus pallidus (GPi) and the size of the GPi, 2 electrodes were designed in order to improve the therapeutic benefit, to minimize side effects from DBS and to obtain a more homogeneous electric field distribution. The electrodes were evaluated numerically by using a stereotactic model measuring the correlation between the electric field and the GPi. The model was applied to 26 dystonodyskinetic patients who underwent surgery for a bilateral lead implantation into the posteroventral part of the GPi. The designed electrodes produced a more homogeneous distribution of the electric field than the quadripolar electrode.

  13. Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes

    PubMed Central

    Howell, Bryan; Huynh, Brian; Grill, Warren M.

    2015-01-01

    Objective Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS. Approach We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo. Main results Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45–84 % less power. Similar gains in selectivity were evident with the optimized electrodes: 50 % of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44–48 % with the standard electrode to 0–14 % with bipolar designs; 50 % of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53–55 % with the standard electrode to 1–5 % with an array of cathodes; and, 50 % of TAs could be activated while reducing activation of AOPs from 43–100 % with the standard electrode to 2–15 % with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation. Significance Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes. PMID:26170244

  14. Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes

    NASA Astrophysics Data System (ADS)

    Howell, Bryan; Huynh, Brian; Grill, Warren M.

    2015-08-01

    Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS. Approach. We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo. Main results. Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45-84% less power. Similar gains in selectivity were evident with the optimized electrodes: 50% of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44 to 48% with the standard electrode to 0-14% with bipolar designs; 50% of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53 to 55% with the standard electrode to 1-5% with an array of cathodes; and, 50% of TAs could be activated while reducing activation of AOPs from 43 to 100% with the standard electrode to 2-15% with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation. Significance. Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes.

  15. Analysis of electrodes' placement and deformation in deep brain stimulation from medical images

    NASA Astrophysics Data System (ADS)

    Mehri, Maroua; Lalys, Florent; Maumet, Camille; Haegelen, Claire; Jannin, Pierre

    2012-02-01

    Deep brain stimulation (DBS) is used to reduce the motor symptoms such as rigidity or bradykinesia, in patients with Parkinson's disease (PD). The Subthalamic Nucleus (STN) has emerged as prime target of DBS in idiopathic PD. However, DBS surgery is a difficult procedure requiring the exact positioning of electrodes in the pre-operative selected targets. This positioning is usually planned using patients' pre-operative images, along with digital atlases, assuming that electrode's trajectory is linear. However, it has been demonstrated that anatomical brain deformations induce electrode's deformations resulting in errors in the intra-operative targeting stage. In order to meet the need of a higher degree of placement accuracy and to help constructing a computer-aided-placement tool, we studied the electrodes' deformation in regards to patients' clinical data (i.e., sex, mean PD duration and brain atrophy index). Firstly, we presented an automatic algorithm for the segmentation of electrode's axis from post-operative CT images, which aims to localize the electrodes' stimulated contacts. To assess our method, we applied our algorithm on 25 patients who had undergone bilateral STNDBS. We found a placement error of 0.91+/-0.38 mm. Then, from the segmented axis, we quantitatively analyzed the electrodes' curvature and correlated it with patients' clinical data. We found a positive significant correlation between mean curvature index of the electrode and brain atrophy index for male patients and between mean curvature index of the electrode and mean PD duration for female patients. These results help understanding DBS electrode' deformations and would help ensuring better anticipation of electrodes' placement.

  16. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD.

    PubMed

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R; Huang, He; Guthrie, Barton L; Watts, Ray L; Walker, Harrison C

    2011-09-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case-control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while PD controls without DBS lost 0.8 ± 1.1 kg. Although bilateral STN DBS patients gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference was not statistically significant (P = 0.885). Although there was a trend toward greater weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode.

  17. Analysis of deep brain stimulation electrode characteristics for neural recording

    NASA Astrophysics Data System (ADS)

    Kent, Alexander R.; Grill, Warren M.

    2014-08-01

    Objective. Closed-loop deep brain stimulation (DBS) systems have the potential to optimize treatment of movement disorders by enabling automatic adjustment of stimulation parameters based on a feedback signal. Evoked compound action potentials (ECAPs) and local field potentials (LFPs) recorded from the DBS electrode may serve as suitable closed-loop control signals. The objective of this study was to understand better the factors that influence ECAP and LFP recording, including the physical presence of the electrode, the geometrical dimensions of the electrode, and changes in the composition of the peri-electrode space across recording conditions. Approach. Coupled volume conductor-neuron models were used to calculate single-unit activity as well as ECAP responses and LFP activity from a population of model thalamic neurons. Main results. Comparing ECAPs and LFPs measured with and without the presence of the highly conductive recording contacts, we found that the presence of these contacts had a negligible effect on the magnitude of single-unit recordings, ECAPs (7% RMS difference between waveforms), and LFPs (5% change in signal magnitude). Spatial averaging across the contact surface decreased the ECAP magnitude in a phase-dependent manner (74% RMS difference), resulting from a differential effect of the contact on the contribution from nearby or distant elements, and decreased the LFP magnitude (25% change). Reductions in the electrode diameter or recording contact length increased signal energy and increased spatial sensitivity of single neuron recordings. Moreover, smaller diameter electrodes (500 µm) were more selective for recording from local cells over passing axons, with the opposite true for larger diameters (1500 µm). Changes in electrode dimensions had phase-dependent effects on ECAP characteristics, and generally had small effects on the LFP magnitude. ECAP signal energy and LFP magnitude decreased with tighter contact spacing (100 µm), compared to

  18. Analysis of deep brain stimulation electrode characteristics for neural recording

    PubMed Central

    Kent, Alexander R.; Grill, Warren M.

    2014-01-01

    Closed-loop deep brain stimulation (DBS) systems have the potential to optimize treatment of movement disorders by enabling automatic adjustment of stimulation parameters based on a feedback signal. Evoked compound action potentials (ECAPs) and local field potentials (LFPs) recorded from the DBS electrode may serve as suitable closed-loop control signals. The objective of this study was to understand better the factors that influence ECAP and LFP recording, including the physical presence of the electrode, the geometrical dimensions of the electrode, and changes in the composition of the peri-electrode space across recording conditions. Coupled volume conductor-neuron models were used to calculate single-unit activity as well as ECAP responses and LFP activity from a population of model thalamic neurons. Comparing ECAPs and LFPs measured with and without the presence of the highly conductive recording contacts, we found that the presence of these contacts had a negligible effect on the magnitude of single-unit recordings, ECAPs (7% RMS difference between waveforms), and LFPs (5% change in signal magnitude). Spatial averaging across the contact surface decreased the ECAP magnitude in a phase-dependent manner (74% RMS difference), resulting from a differential effect of the contact on the contribution from nearby or distant elements, and decreased the LFP magnitude (25% change). Reductions in the electrode diameter or recording contact length increased signal energy and increased spatial sensitivity of single neuron recordings. Moreover, smaller diameter electrodes (500 µm) were more selective for recording from local cells over passing axons, with the opposite true for larger diameters (1500 µm). Changes in electrode dimensions had phase-dependent effects on ECAP characteristics, and generally had small effects on the LFP magnitude. ECAP signal energy and LFP magnitude decreased with tighter contact spacing (100 µm), compared to the original dimensions (1500 µm

  19. DBS for Obesity

    PubMed Central

    Franco, Ruth; Fonoff, Erich T.; Alvarenga, Pedro; Lopes, Antonio Carlos; Miguel, Euripides C.; Teixeira, Manoel J.; Damiani, Durval; Hamani, Clement

    2016-01-01

    Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity. PMID:27438859

  20. Preclinical evaluation of a miniaturized Deep Brain Stimulation electrode lead.

    PubMed

    Villalobos, Joel; Fallon, James B; McNeill, Peter M; Allison, Rachel K; Bibari, Olivier; Williams, Chris E; McDermott, Hugh J

    2015-01-01

    The effect of miniaturizing the electrode lead for Deep Brain Stimulation (DBS) therapy was investigated in this work. A direct comparison was made between a miniature lead (0.65 mm diameter) and a lead of standard size (1.3 mm). Acute in vivo implantation in two cat brains was performed to evaluate surgical trauma and confirm capacity to target thalamic nuclei. Insertion into a homogeneous gel model of neural tissue was used to compare insertion forces while visualizing the process. The standard size cannula, used first to guide lead insertion, required substantially higher insertion force compared with the miniature version and produced a significantly larger region of tissue disruption. The characteristic hemorrhage and edema extended 119-352 μm from the implanted track surface of the miniature lead and cannula, while these extended 311-571 μm for the standard size lead and cannula. A miniature DBS implant can reduce the extent of trauma and could potentially help improve neural function preservation after functional neurosurgery.

  1. Fiber-based tissue identification for electrode placement in deep brain stimulation neurosurgery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    DePaoli, Damon T.; Lapointe, Nicolas; Goetz, Laurent; Parent, Martin; Prudhomme, Michel; Cantin, Léo.; Galstian, Tigran; Messaddeq, Younès.; Côté, Daniel C.

    2016-03-01

    Deep brain stimulation's effectiveness relies on the ability of the stimulating electrode to be properly placed within a specific target area of the brain. Optical guidance techniques that can increase the accuracy of the procedure, without causing any additional harm, are therefore of great interest. We have designed a cheap optical fiber-based device that is small enough to be placed within commercially available DBS stimulating electrodes' hollow cores and that is capable of sensing biological information from the surrounding tissue, using low power white light. With this probe we have shown the ability to distinguish white and grey matter as well as blood vessels, in vitro, in human brain samples and in vivo, in rats. We have also repeated the in vitro procedure with the probe inserted in a DBS stimulating electrode and found the results were in good agreement. We are currently validating a second fiber optic device, with micro-optical components, that will result in label free, molecular level sensing capabilities, using CARS spectroscopy. The final objective will be to use this data in real time, during deep brain stimulation neurosurgery, to increase the safety and accuracy of the procedure.

  2. Dynamic tension EMG to characterize the effects of DBS treatment of advanced Parkinson's disease.

    PubMed

    Ruonala, V; Pekkonen, E; Rissanen, S; Airaksinen, O; Miroshnichenko, G; Kankaanpää, M; Karjalainen, P

    2014-01-01

    Deep brain stimulation (DBS) is an effective treatment method for motor symptoms of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic nucleus to give precisely allocated electrical stimuli to brain. The optimal stimulus type has to be adjusted individually. Disease severity, main symptoms and biological factors play a role in correctly setting up the device. Currently there are no objective methods to assess the efficacy of DBS, hence the adjustment is based solely on clinical assessment. In optimal case an objectively measurable feature would point the right settings of DBS. Surface electromyographic and kinematic measurements have been used in Parkinson's disease research. As Parkinson's disease symptoms are known to change the EMG signal properties, these methods could be helpful aid in the clinical adjustment of DBS. In this study, 13 patients with advanced Parkinson's disease who received DBS treatment were measured. The patients were measured with seven different settings of the DBS in clinical range including changes in stimulation amplitude, frequency and pulse width. The EMG analysis was based on parameters that characterize EMG signal morphology. Correlation dimension and recurrence rate made the most significant difference in relation to optimal settings. In conclusion, EMG analysis is able to detect differences between the DBS setups, and can help in finding the correct parameters.

  3. Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease—A Computational Study

    PubMed Central

    Mandali, Alekhya; Chakravarthy, V. Srinivasa; Rajan, Roopa; Sarma, Sankara; Kishore, Asha

    2016-01-01

    Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients. PMID:27965590

  4. Investigating the depth electrode-brain interface in deep brain stimulation using finite element models with graded complexity in structure and solution.

    PubMed

    Yousif, Nada; Liu, Xuguang

    2009-10-30

    Deep brain stimulation (DBS) is an increasingly used surgical therapy for a range of neurological disorders involving the long-term electrical stimulation of various regions of the human brain in a disorder specific manner. Despite being used for the last 20 years, the underlying mechanisms are still not known, and disputed. In particular, when the electrodes are implanted into the human brain, an interface is created with changing biophysical properties which may impact on stimulation. We previously defined the electrode-brain interface (EBI) as consisting of three structural elements: the quadripolar DBS electrode, the peri-electrode space and the surrounding brain tissue. In order to understand more about the nature of this EBI, we used structural computational models of this interface, and estimated the effects of stimulation using coupled axon models. These finite element models differ in complexity, each highlighting a different feature of the EBI's effect on the DBS-induced electric field. We show that the quasi-static models are sufficient to demonstrate the difference between the acute and chronic clinical stages post-implantation. However, the frequency-dependent models are necessary as the waveform shaping has a major influence on the activation of neuronal fibres. We also investigate anatomical effects on the electric field, by taking specific account of the ventricular system in the human brain. Taken together, these models allow us to visualise the static, dynamic and target specific properties of the DBS-induced field in the surrounding brain regions.

  5. Mood Response to Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson Disease

    PubMed Central

    Campbell, Meghan C.; Black, Kevin J.; Weaver, Patrick M.; Lugar, Heather M.; Videen, Tom O.; Tabbal, Samer D.; Karimi, Morvarid; Perlmutter, Joel S.; Hershey, Tamara

    2012-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson disease (PD) improves motor function but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. We identified the anatomical location of electrode contacts and measured mood response to stimulation with the Visual Analog Scale in 24 STN DBS PD patients. Participants reported greater positive mood, decreased anxiety and apathy with bilateral and unilateral stimulation. Left DBS improved mood more than right DBS. Right DBS-induced increase in positive mood was related to more medial and dorsal contact locations. These results highlight the functional heterogeneity of the STN. PMID:22450611

  6. Model-Based Comparison of Deep Brain Stimulation Array Functionality with Varying Number of Radial Electrodes and Machine Learning Feature Sets.

    PubMed

    Teplitzky, Benjamin A; Zitella, Laura M; Xiao, YiZi; Johnson, Matthew D

    2016-01-01

    Deep brain stimulation (DBS) leads with radially distributed electrodes have potential to improve clinical outcomes through more selective targeting of pathways and networks within the brain. However, increasing the number of electrodes on clinical DBS leads by replacing conventional cylindrical shell electrodes with radially distributed electrodes raises practical design and stimulation programming challenges. We used computational modeling to investigate: (1) how the number of radial electrodes impact the ability to steer, shift, and sculpt a region of neural activation (RoA), and (2) which RoA features are best used in combination with machine learning classifiers to predict programming settings to target a particular area near the lead. Stimulation configurations were modeled using 27 lead designs with one to nine radially distributed electrodes. The computational modeling framework consisted of a three-dimensional finite element tissue conductance model in combination with a multi-compartment biophysical axon model. For each lead design, two-dimensional threshold-dependent RoAs were calculated from the computational modeling results. The models showed more radial electrodes enabled finer resolution RoA steering; however, stimulation amplitude, and therefore spatial extent of the RoA, was limited by charge injection and charge storage capacity constraints due to the small electrode surface area for leads with more than four radially distributed electrodes. RoA shifting resolution was improved by the addition of radial electrodes when using uniform multi-cathode stimulation, but non-uniform multi-cathode stimulation produced equivalent or better resolution shifting without increasing the number of radial electrodes. Robust machine learning classification of 15 monopolar stimulation configurations was achieved using as few as three geometric features describing a RoA. The results of this study indicate that, for a clinical-scale DBS lead, more than four radial

  7. Model-Based Comparison of Deep Brain Stimulation Array Functionality with Varying Number of Radial Electrodes and Machine Learning Feature Sets

    PubMed Central

    Teplitzky, Benjamin A.; Zitella, Laura M.; Xiao, YiZi; Johnson, Matthew D.

    2016-01-01

    Deep brain stimulation (DBS) leads with radially distributed electrodes have potential to improve clinical outcomes through more selective targeting of pathways and networks within the brain. However, increasing the number of electrodes on clinical DBS leads by replacing conventional cylindrical shell electrodes with radially distributed electrodes raises practical design and stimulation programming challenges. We used computational modeling to investigate: (1) how the number of radial electrodes impact the ability to steer, shift, and sculpt a region of neural activation (RoA), and (2) which RoA features are best used in combination with machine learning classifiers to predict programming settings to target a particular area near the lead. Stimulation configurations were modeled using 27 lead designs with one to nine radially distributed electrodes. The computational modeling framework consisted of a three-dimensional finite element tissue conductance model in combination with a multi-compartment biophysical axon model. For each lead design, two-dimensional threshold-dependent RoAs were calculated from the computational modeling results. The models showed more radial electrodes enabled finer resolution RoA steering; however, stimulation amplitude, and therefore spatial extent of the RoA, was limited by charge injection and charge storage capacity constraints due to the small electrode surface area for leads with more than four radially distributed electrodes. RoA shifting resolution was improved by the addition of radial electrodes when using uniform multi-cathode stimulation, but non-uniform multi-cathode stimulation produced equivalent or better resolution shifting without increasing the number of radial electrodes. Robust machine learning classification of 15 monopolar stimulation configurations was achieved using as few as three geometric features describing a RoA. The results of this study indicate that, for a clinical-scale DBS lead, more than four radial

  8. Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS

    PubMed Central

    Hartmann, Christian J.; Lujan, J. Luis; Chaturvedi, Ashutosh; Goodman, Wayne K.; Okun, Michael S.; McIntyre, Cameron C.; Haq, Ihtsham U.

    2016-01-01

    Background: Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS. Methods: We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS. Results: Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non-responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results. Discussion: Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes. PMID:26834544

  9. DBS-relevant electric fields increase hydraulic conductivity of in vitro endothelial monolayers.

    PubMed

    Lopez-Quintero, S V; Datta, A; Amaya, R; Elwassif, M; Bikson, M; Tarbell, J M

    2010-02-01

    Deep brain stimulation (DBS) achieves therapeutic outcome through generation of electric fields (EF) in the vicinity of energized electrodes. Targeted brain regions are highly vascularized, and it remains unknown if DBS electric fields modulate blood-brain barrier (BBB) function, either through electroporation of individual endothelial cells or electro-permeation of barrier tight junctions. In our study, we calculated the intensities of EF generated around energized Medtronic 3387 and 3389 DBS leads by using a finite element model. Then we designed a novel stimulation system to study the effects of such fields with DBS-relevant waveforms and intensities on bovine aortic endothelial cell (BAEC) monolayers, which were used as a basic analog for the blood-brain barrier endothelium. Following 5 min of stimulation, we observed a transient increase in endothelial hydraulic conductivity (Lp) that could be related to the disruption of the tight junctions (TJ) between cells, as suggested by zonula occludens-1 (ZO-1) protein staining. This 'electro-permeation' occurred in the absence of cell death or single cell electroporation, as indicated by propidium iodide staining and cytosolic calcein uptake. Our in vitro results, using uniform fields and BAEC monolayers, thus suggest that electro-permeation of the BBB may occur at electric field intensities below those inducing electroporation and within intensities generated near DBS electrodes. Further studies are necessary to address potential BBB disruption during clinical studies, with safety and efficacy implications.

  10. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    PubMed Central

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-01-01

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

  11. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation.

    PubMed

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-07-16

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  12. CMOS-based smart-electrode-type retinal stimulator with bullet-shaped bulk Pt electrodes.

    PubMed

    Tokuda, T; Ito, T; Kitao, T; Noda, T; Sasagawa, K; Terasawa, Y; Tashiro, H; Kanda, H; Fujikado, T; Ohta, J

    2011-01-01

    A CMOS-based flexible retinal stimulator equipped with bullet-shaped bulk Pt electrodes was fabricated and demonstrated. We designed a new CMOS unit chip with an on-chip stimulator, single- and multi-site stimulation modes, and monitoring functions. We have developed a new structure and packaging process of flexible retinal stimulator with bullet-type bulk Pt electrode. We have confirmed the retinal stimulation functionality in an in vivo stimulation trial on rabbit's retina.

  13. Feedback control of electrode offset voltage during functional electrical stimulation.

    PubMed

    Chu, Jun-Uk; Song, Kang-Il; Shon, Ahnsei; Han, Sungmin; Lee, Soo Hyun; Kang, Ji Yoon; Hwang, Dosik; Suh, Jun-Kyo Francis; Choi, Kuiwon; Youn, Inchan

    2013-08-15

    Control of the electrode offset voltage is an important issue related to the processes of functional electrical stimulation because excess charge accumulation over time damages both the tissue and the electrodes. This paper proposes a new feedback control scheme to regulate the electrode offset voltage to a predetermined reference value. The electrode offset voltage was continuously monitored using a sample-and-hold (S/H) circuit during stimulation and non-stimulation periods. The stimulation current was subsequently adjusted using a proportional-integral (PI) controller to minimise the error between the reference value and the electrode offset voltage. During the stimulation period, the electrode offset voltage was maintained through the S/H circuit, and the PI controller did not affect the amplitude of the stimulation current. In contrast, during the non-stimulation period, the electrode offset voltage was sampled through the S/H circuit and rapidly regulated through the PI controller. The experimental results obtained using a nerve cuff electrode showed that the electrode offset voltage was successfully controlled in terms of the performance specifications, such as the steady- and transient-state responses and the constraint of the controller output. Therefore, the proposed control scheme can potentially be used in various nerve stimulation devices and applications requiring control of the electrode offset voltage.

  14. Subject-specific computational modeling of DBS in the PPTg area

    PubMed Central

    Zitella, Laura M.; Teplitzky, Benjamin A.; Yager, Paul; Hudson, Heather M.; Brintz, Katelynn; Duchin, Yuval; Harel, Noam; Vitek, Jerrold L.; Baker, Kenneth B.; Johnson, Matthew D.

    2015-01-01

    Deep brain stimulation (DBS) in the pedunculopontine tegmental nucleus (PPTg) has been proposed to alleviate medically intractable gait difficulties associated with Parkinson's disease. Clinical trials have shown somewhat variable outcomes, stemming in part from surgical targeting variability, modulating fiber pathways implicated in side effects, and a general lack of mechanistic understanding of DBS in this brain region. Subject-specific computational models of DBS are a promising tool to investigate the underlying therapy and side effects. In this study, a parkinsonian rhesus macaque was implanted unilaterally with an 8-contact DBS lead in the PPTg region. Fiber tracts adjacent to PPTg, including the oculomotor nerve, central tegmental tract, and superior cerebellar peduncle, were reconstructed from a combination of pre-implant 7T MRI, post-implant CT, and post-mortem histology. These structures were populated with axon models and coupled with a finite element model simulating the voltage distribution in the surrounding neural tissue during stimulation. This study introduces two empirical approaches to evaluate model parameters. First, incremental monopolar cathodic stimulation (20 Hz, 90 μs pulse width) was evaluated for each electrode, during which a right eyelid flutter was observed at the proximal four contacts (−1.0 to −1.4 mA). These current amplitudes followed closely with model predicted activation of the oculomotor nerve when assuming an anisotropic conduction medium. Second, PET imaging was collected OFF-DBS and twice during DBS (two different contacts), which supported the model predicted activation of the central tegmental tract and superior cerebellar peduncle. Together, subject-specific models provide a framework to more precisely predict pathways modulated by DBS. PMID:26236229

  15. Anatomo-clinical correlation of intraoperative stimulation-induced side-effects during HF-DBS of the subthalamic nucleus.

    PubMed

    Tamma, F; Caputo, E; Chiesa, V; Egidi, M; Locatelli, M; Rampini, P; Cinnante, C; Pesenti, A; Priori, A

    2002-09-01

    The efficacy of deep brain stimulation of the subthalamic nucleus (STN) is dependent on the accuracy of targeting. In order to reduce the number of passes and, consequently, the duration of surgery and risk of bleeding, we have set up a new method based on direct magnetic resonance imaging (MRI) localisation of the STN. This procedure allows a short duration of the neurophysiological session (one or two initial tracks). Whenever a supplementary track is needed, the stimulation-induced side effects are analysed to choose from one of the remaining holes in Ben's gun. A good knowledge of anatomical structures surrounding the STN is mandatory to relate side effects to the actual position of the track. In our series of 11 patients (22 sides, 37 tracks), the most common and reproducible side effects were those characterised by motor, sensorial, oculomotor and vegetative signs and symptoms. Moreover, the therapeutic window (distance between the current intensity needed to obtain the best clinical effect and the intensity capable to induce side effects) predicted clinical efficacy in the long-term, and contributed to the choice of which among the examined tracks had to be implanted with the chronic macroelectrode.

  16. Method for patient-specific finite element modeling and simulation of deep brain stimulation.

    PubMed

    Aström, Mattias; Zrinzo, Ludvic U; Tisch, Stephen; Tripoliti, Elina; Hariz, Marwan I; Wårdell, Karin

    2009-01-01

    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.

  17. Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD).

    PubMed

    Makris, Nikolaos; Rathi, Yogesh; Mouradian, Palig; Bonmassar, Giorgio; Papadimitriou, George; Ing, Wingkwai I; Yeterian, Edward H; Kubicki, Marek; Eskandar, Emad N; Wald, Lawrence L; Fan, Qiuyun; Nummenmaa, Aapo; Widge, Alik S; Dougherty, Darin D

    2016-12-01

    Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.

  18. MRI-Based Multiscale Model for Electromagnetic Analysis in the Human Head with Implanted DBS

    PubMed Central

    Iacono, Maria Ida; Makris, Nikos; Mainardi, Luca; Angelone, Leonardo M.; Bonmassar, Giorgio

    2013-01-01

    Deep brain stimulation (DBS) is an established procedure for the treatment of movement and affective disorders. Patients with DBS may benefit from magnetic resonance imaging (MRI) to evaluate injuries or comorbidities. However, the MRI radio-frequency (RF) energy may cause excessive tissue heating particularly near the electrode. This paper studies how the accuracy of numerical modeling of the RF field inside a DBS patient varies with spatial resolution and corresponding anatomical detail of the volume surrounding the electrodes. A multiscale model (MS) was created by an atlas-based segmentation using a 1 mm3 head model (mRes) refined in the basal ganglia by a 200 μm2 ex-vivo dataset. Four DBS electrodes targeting the left globus pallidus internus were modeled. Electromagnetic simulations at 128 MHz showed that the peak of the electric field of the MS doubled (18.7 kV/m versus 9.33 kV/m) and shifted 6.4 mm compared to the mRes model. Additionally, the MS had a sixfold increase over the mRes model in peak-specific absorption rate (SAR of 43.9 kW/kg versus 7 kW/kg). The results suggest that submillimetric resolution and improved anatomical detail in the model may increase the accuracy of computed electric field and local SAR around the tip of the implant. PMID:23956789

  19. Single Electrode Deep Brain Stimulation with Dual Targeting at Dual Frequency for the Treatment of Chronic Pain: A Case Series and Review of the Literature

    PubMed Central

    Hollingworth, Milo; Sims-Williams, Hugh P.; Pickering, Anthony E.; Barua, Neil; Patel, Nikunj K.

    2017-01-01

    Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimize management of patients with complex pain symptomatology. However, previous attempts to stimulate multiple targets requires multiple trajectories and considerable expense. Using a single electrode to stimulate multiple targets would help overcome these challenges. A pre-requisite of such a technique is the ability to use different stimulation parameters at different contacts simultaneously on the same electrode. We describe a novel technique in 3 patients with chronic pain syndromes for whom conventional medical and/or neuromodulation therapy had failed using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies. PMID:28098766

  20. Deep brain stimulation for refractory epilepsy

    PubMed Central

    Mandat, Tomasz; Kornakiewicz, Anna; Koziara, Henryk; Nauman, Paweł

    2012-01-01

    Deep brain stimulation (DBS) is a method of treatment utilized to control medically refractory epilepsy (RE). Patients with medically refractory epilepsy who do not achieve satisfactory control of seizures with pharmacological treatment or surgical resection of the epileptic focus and those who do not qualify for surgery could benefit from DBS. The most frequently used stereotactic targets for DBS are the anterior thalamic nucleus, subthalamic nucleus, central-medial thalamic nucleus, hippocampus, amygdala and cerebellum. The DBS is believed to be an effective method of treatment for various types of epilepsy among adults and adolescents. Side effects may be associated with implantation of electrodes and with the stimulation itself. An increasing number of publications and growing interest in DBS application for RE may result in standardization of the qualification and treatment protocol for RE with DBS. PMID:23185188

  1. Analysis of fractal electrodes for efficient neural stimulation

    PubMed Central

    Golestanirad, Laleh; Elahi, Behzad; Molina, Alberto; Mosig, Juan R.; Pollo, Claudio; Chen, Robert; Graham, Simon J.

    2013-01-01

    Planar electrodes are increasingly used in therapeutic neural stimulation techniques such as functional electrical stimulation, epidural spinal cord stimulation (ESCS), and cortical stimulation. Recently, optimized electrode geometries have been shown to increase the efficiency of neural stimulation by increasing the variation of current density on the electrode surface. In the present work, a new family of modified fractal electrode geometries is developed to enhance the efficiency of neural stimulation. It is shown that a promising approach in increasing the neural activation function is to increase the “edginess” of the electrode surface, a concept that is explained and quantified by fractal mathematics. Rigorous finite element simulations were performed to compute electric potential produced by proposed modified fractal geometries. The activation of 256 model axons positioned around the electrodes was then quantified, showing that modified fractal geometries required a 22% less input power while maintaining the same level of neural activation. Preliminary in vivo experiments investigating muscle evoked potentials due to median nerve stimulation showed encouraging results, supporting the feasibility of increasing neural stimulation efficiency using modified fractal geometries. PMID:23874290

  2. Heating induced near deep brain stimulation lead electrodes during magnetic resonance imaging with a 3 T transceive volume head coil

    NASA Astrophysics Data System (ADS)

    Shrivastava, Devashish; Abosch, Aviva; Hughes, John; Goerke, Ute; DelaBarre, Lance; Visaria, Rachana; Harel, Noam; Vaughan, J. Thomas

    2012-09-01

    Heating induced near deep brain stimulation (DBS) lead electrodes during magnetic resonance imaging with a 3 T transceive head coil was measured, modeled, and imaged in three cadaveric porcine heads (mean body weight = 85.47 ± 3.19 kg, mean head weight = 5.78 ± 0.32 kg). The effect of the placement of the extra-cranial portion of the DBS lead on the heating was investigated by looping the extra-cranial lead on the top, side, and back of the head, and placing it parallel to the coil's longitudinal axial direction. The heating was induced using a 641 s long turbo spin echo sequence with the mean whole head average specific absorption rate of 3.16 W kg-1. Temperatures were measured using fluoroptic probes at the scalp, first and second electrodes from the distal lead tip, and 6 mm distal from electrode 1 (T6 mm). The heating was modeled using the maximum T6 mm and imaged using a proton resonance frequency shift-based MR thermometry method. Results showed that the heating was significantly reduced when the extra-cranial lead was placed in the longitudinal direction compared to the other placements (peak temperature change = 1.5-3.2 °C versus 5.1-24.7 °C). Thermal modeling and MR thermometry may be used together to determine the heating and improve patient safety online.

  3. Heating induced near deep brain stimulation lead electrodes during magnetic resonance imaging with a 3 T transceive volume head coil.

    PubMed

    Shrivastava, Devashish; Abosch, Aviva; Hughes, John; Goerke, Ute; DelaBarre, Lance; Visaria, Rachana; Harel, Noam; Vaughan, J Thomas

    2012-09-07

    Heating induced near deep brain stimulation (DBS) lead electrodes during magnetic resonance imaging with a 3 T transceive head coil was measured, modeled, and imaged in three cadaveric porcine heads (mean body weight = 85.47 ± 3.19 kg, mean head weight = 5.78 ± 0.32 kg). The effect of the placement of the extra-cranial portion of the DBS lead on the heating was investigated by looping the extra-cranial lead on the top, side, and back of the head, and placing it parallel to the coil's longitudinal axial direction. The heating was induced using a 641 s long turbo spin echo sequence with the mean whole head average specific absorption rate of 3.16 W kg(-1). Temperatures were measured using fluoroptic probes at the scalp, first and second electrodes from the distal lead tip, and 6 mm distal from electrode 1 (T(6 mm)). The heating was modeled using the maximum T(6 mm) and imaged using a proton resonance frequency shift-based MR thermometry method. Results showed that the heating was significantly reduced when the extra-cranial lead was placed in the longitudinal direction compared to the other placements (peak temperature change = 1.5-3.2 °C versus 5.1-24.7 °C). Thermal modeling and MR thermometry may be used together to determine the heating and improve patient safety online.

  4. Characterization of electrical stimulation electrodes for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Cannizzaro, Chris; Figallo, Elisa; Voldman, Joel; Vunjak-Novakovic, Gordana

    2006-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. The goal of this study was to assess the conditions of electrical stimulation with respect to the electrode geometry, material properties and charge-transfer characteristics at the electrode-electrolyte interface. We compared various biocompatible materials, including nanoporous carbon, stainless steel, titanium and titanium nitride, for use in cardiac tissue engineering bioreactors. The faradaic and non-faradaic charge transfer mechanisms were assessed by electrochemical impedance spectroscopy (EIS), studying current injection characteristics, and examining surface properties of electrodes with scanning electron microscopy. Carbon electrodes were found to have the best current injection characteristics. However, these electrodes require careful handling because of their limited mechanical strength. The efficacy of various electrodes for use in 2-D and 3-D cardiac tissue engineering systems with neonatal rat cardiomyocytes is being determined by assessing cell viability, amplitude of contractions, excitation thresholds, maximum capture rate, and tissue morphology.

  5. Multi-Electrode Array for Transcutaneous Lumbar Posterior Root Stimulation.

    PubMed

    Krenn, Matthias; Hofstoetter, Ursula S; Danner, Simon M; Minassian, Karen; Mayr, Winfried

    2015-10-01

    Interest in transcutaneous electrical stimulation of the lumbosacral spinal cord is increasing in human electrophysiological and clinical studies. The stimulation effects on lower limb muscles depend on the depolarization of segmentally organized posterior root afferents and, thus, the rostro-caudal stimulation site. In previous studies, selective stimulation was achieved by varying the positions of single self-adhesive electrodes over the thoracolumbar spine. Here, we developed a multi-electrode surface array consisting of 3 × 8 electrode pads and tested its stimulation-site specificity. The array was placed longitudinally over the spine covering the T10-L2 vertebrae. Two different hydrogel layer configurations were utilized: a single layer adhered to all electrode pads of the array and a configuration comprised of eight separate strips attached to the three transverse electrode pads of each level. Voltage measurements demonstrated that an effectively focused field distribution along the longitudinal extent of the array was not accomplished when using the single continuous hydrogel layer, and segmental selective stimulation of the posterior root afferents was not possible. The separate strips produced a focused electric field distribution at the rostro-caudal level of the electrode pads selected for stimulation. This configuration allowed for the preferential elicitation of posterior root-muscle reflexes in either the L2-L4 innervated quadriceps or the L5-S2 innervated triceps surae muscle groups. Such multi-electrode array for transcutaneous spinal cord stimulation shall allow for improved control of stimulation conditions in electrophysiological studies and time-dependent and site-specific stimulation patterns for neuromodulation applications.

  6. Tractography-activation models applied to subcallosal cingulate deep brain stimulation.

    PubMed

    Lujan, J Luis; Chaturvedi, Ashutosh; Choi, Ki Sueng; Holtzheimer, Paul E; Gross, Robert E; Mayberg, Helen S; McIntyre, Cameron C

    2013-09-01

    Deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCWM) is an experimental therapy for major depressive disorder (MDD). The specific axonal pathways that mediate the anti-depressant effects of DBS remain unknown. Patient-specific tractography-activation models (TAMs) are a new tool to help identify pathways modulated by DBS. TAMs consist of four basic components: 1) anatomical and diffusion-weighted imaging data acquired on the patient; 2) probabilistic tractography from the brain region surrounding the implanted DBS electrode; 3) finite element models of the electric field generated by the patient-specific DBS parameter settings; and 4) application of the DBS electric field to multi-compartment cable models of axons, with trajectories defined by the tractography, to predict action potential generation in specific pathways. This study presents TAM predictions from DBS of the SCCWM in one MDD patient. Our findings suggest that small differences in electrode location can generate substantial differences in the directly activated pathways.

  7. Electrodes for bio-application: recording and stimulation

    NASA Astrophysics Data System (ADS)

    Fontes, M. B. A.

    2013-03-01

    Recording and stimulation electrodes applied on excitable tissue are the basis of electrophysiological research, such as brain, muscles, peripheral nerves or sensory systems. Electrode-electrolyte impedance is one of the important characteristics due to its influence on the signal/noise ratio, signal distortion and built-up voltage. Strategies to lowering and tuning the impedance are achieved by biasing iridium oxide modified platinum microelectrodes. Surface and impedance analysis after pulse stimulation are also addressed.

  8. Transcranial direct current stimulation: electrode montage in stroke.

    PubMed

    Mahmoudi, Hooman; Borhani Haghighi, Afshin; Petramfar, Peyman; Jahanshahi, Sepehr; Salehi, Zahra; Fregni, Felipe

    2011-01-01

    Neurophysiological and computer modelling studies have shown that electrode montage is a critical parameter to determine the neuromodulatory effects of transcranial direct current stimulation (tDCS). We tested these results clinically by systematically investigating optimal tDCS electrode montage in stroke. Ten patients received in a counterbalanced and randomised order the following conditions of stimulation (i) anodal stimulation of affected M1 (primary motor cortex) and cathodal stimulation of unaffected M1 ('bilateral tDCS'); (ii) anodal stimulation of affected M1 and cathodal stimulation of contralateral supraorbital area ('anodal tDCS'); (iii) cathodal stimulation of unaffected M1 and anodal stimulation of contralateral supraorbital area ('cathodal tDCS'); (iv) anodal stimulation of affected M1 and cathodal stimulation of contralateral deltoid muscle ('extra-cephalic tDCS') and (v) sham stimulation. We used the Jebsen-Taylor Test (JTT) as a widely accepted measure of upper limb function. Bilateral tDCS, anodal tDCS and cathodal tDCS were shown to be associated with significant improvements on the JTT. Placing the reference electrode in an extracephalic position and use of sham stimulation did not induce any significant effects. This small sham controlled cross-over clinical trial is important to provide additional data on the clinical effects of tDCS in stroke and for planning and designing future large tDCS trials in patients with stroke.

  9. Computational analysis of deep brain stimulation.

    PubMed

    McIntyre, Cameron C; Miocinovic, Svjetlana; Butson, Christopher R

    2007-09-01

    Chronic, high-frequency electrical stimulation of subcortical brain structures (deep brain stimulation [DBS]) is an effective clinical treatment for several medically refractory neurological disorders. However, the clinical successes of DBS are tempered by the limited understanding of the response of neurons to applied electric fields and scientific definition of the therapeutic mechanisms of DBS remains elusive. In addition, it is presently unclear which electrode designs and stimulation parameters are optimal for maximum therapeutic benefit and minimal side effects. Detailed computer modeling of DBS has recently emerged as a powerful technique to enhance our understanding of the effects of DBS and to create a virtual testing ground for new stimulation paradigms. This review summarizes the fundamentals of neurostimulation modeling and provides an overview of some of the scientific contributions of computer models to the field of DBS. We then provide a prospective view on the application of DBS-modeling tools to augment the clinical utility of DBS and to design the next generation of DBS technology.

  10. Inclusion and exclusion criteria for DBS in dystonia.

    PubMed

    Bronte-Stewart, Helen; Taira, Takaomi; Valldeoriola, Francesc; Merello, Marcello; Marks, William J; Albanese, Alberto; Bressman, Susan; Moro, Elena

    2011-06-01

    When considering a patient with dystonia for deep brain stimulation (DBS) surgery several factors need to be considered. Level B evidence has shown that all motor features and associated pain in primary generalized and segmental dystonia are potentially responsive to globus pallidus internus (GPi) DBS. However, improvements in clinical series of ≥ 90% may reflect methods that need improvement, and larger prospective studies are needed to address these factors. Nevertheless, to date the selection criteria for DBS-specifically in terms of patient features (severity and nature of symptoms, age, time of evolution, or any other demographic or disease aspects)--have not been assessed in a systematic fashion. In general, dystonia patients are not considered for DBS unless medical therapies have been previously and extensively tested. The vast majority of reported patients have had DBS surgery when the disease was provoking important disability, with loss of independence and impaired quality of life. There does not appear to be an upper age limit or a minimum age limit, although there are no published data regarding the outcome of GPi DBS for dystonia in children younger than 7 years of age. There is currently no enough evidence to prove that subjects with primary--generalized dystonia who undergo DBS at an early age and sooner rather than later after disease onset may gain more benefit from DBS than those undergoing DBS after the development of fixed skeletal deformities. There is no enough evidence to refuse or support consideration of DBS in patients with previous ablative procedures.

  11. In vitro study of iridium electrodes for neural stimulation.

    PubMed

    Aryan, Naser Pour; Brendler, Christian; Rieger, Viola; Schleehauf, Sebastian; Heusel, Gerhard; Rothermel, Albrecht

    2012-01-01

    Iridium is one of the main electrode materials for applications like neural stimulation. Iridium has a higher charge injection capacity when activated and transformed into AIROF (activated iridium oxide film) using specific electrical signals. Activation is not possible in stimulating devices, if they do not include the necessary circuitry for activation. We introduce a method for iridium electrode activation requiring minimum additional on-chip hardware. In the main part, the lifetime behavior of iridium electrodes is investigated. These results may be interesting for applications not including on-chip activation hardware, and also because activation has drawbacks such as worse mechanical properties and reproducibility of AIROF.

  12. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

    PubMed Central

    Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

    2015-01-01

    Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

  13. Computational modeling of an endovascular approach to deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Teplitzky, Benjamin A.; Connolly, Allison T.; Bajwa, Jawad A.; Johnson, Matthew D.

    2014-04-01

    Objective. Deep brain stimulation (DBS) therapy currently relies on a transcranial neurosurgical technique to implant one or more electrode leads into the brain parenchyma. In this study, we used computational modeling to investigate the feasibility of using an endovascular approach to target DBS therapy. Approach. Image-based anatomical reconstructions of the human brain and vasculature were used to identify 17 established and hypothesized anatomical targets of DBS, of which five were found adjacent to a vein or artery with intraluminal diameter ≥1 mm. Two of these targets, the fornix and subgenual cingulate white matter (SgCwm) tracts, were further investigated using a computational modeling framework that combined segmented volumes of the vascularized brain, finite element models of the tissue voltage during DBS, and multi-compartment axon models to predict the direct electrophysiological effects of endovascular DBS. Main results. The models showed that: (1) a ring-electrode conforming to the vessel wall was more efficient at neural activation than a guidewire design, (2) increasing the length of a ring-electrode had minimal effect on neural activation thresholds, (3) large variability in neural activation occurred with suboptimal placement of a ring-electrode along the targeted vessel, and (4) activation thresholds for the fornix and SgCwm tracts were comparable for endovascular and stereotactic DBS, though endovascular DBS was able to produce significantly larger contralateral activation for a unilateral implantation. Significance. Together, these results suggest that endovascular DBS can serve as a complementary approach to stereotactic DBS in select cases.

  14. DBS in the basolateral amygdala improves symptoms of autism and related self-injurious behavior: a case report and hypothesis on the pathogenesis of the disorder

    PubMed Central

    Sturm, Volker; Fricke, Oliver; Bührle, Christian P.; Lenartz, Doris; Maarouf, Mohammad; Treuer, Harald; Mai, Jürgen K.; Lehmkuhl, Gerd

    2013-01-01

    We treated a 13-year-old boy for life-threatening self-injurious behavior (SIB) and severe Kanner's autism with deep brain stimulation (DBS) in the amygdaloid complex as well as in the supra-amygdaloid projection system. Two DBS-electrodes were placed in both structures of each hemisphere. The stimulation contacts targeted the paralaminar, the basolateral (BL), the central amygdala as well as the supra-amygdaloid projection system. DBS was applied to each of these structures, but only stimulation of the BL part proved effective in improving SIB and core symptoms of the autism spectrum in the emotional, social, and even cognitive domains over a follow up of now 24 months. These results, which have been gained for the first time in a patient, support hypotheses, according to which the amygdala may be pivotal in the pathogeneses of autism and point to the special relevance of the BL part. PMID:23346052

  15. Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism.

    PubMed

    Wöhrle, Johannes C; Blahak, Christian; Capelle, Hans-Holger; Fogel, Wolfgang; Bäzner, Hansjoerg; Krauss, Joachim K

    2012-01-01

    Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.

  16. Sputtered iridium oxide for stimulation electrode coatings.

    PubMed

    Mokwa, Wilfried; Wessling, Boerge; Schnakenberg, Uwe

    2007-01-01

    This work deals with the reactive RF-powered sputter deposition of iridium oxide for use as the active stimulation layer in functional medical implants. The oxygen gettered by the growing films is determined by an approach based on generic curves. Films deposited at different stages of oxygen integration show strong differences in electrochemical behaviour, caused by different morphologies. The dependence of electrochemical activity on morphology is further illustrated by RF sputtering onto heated substrates, as well as DC sputtering onto cold substrates.

  17. Bio-heat transfer model of deep brain stimulation-induced temperature changes

    NASA Astrophysics Data System (ADS)

    Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

    2006-12-01

    There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

  18. Attracting retinal cells to electrodes for high-resolution stimulation

    NASA Astrophysics Data System (ADS)

    Palanker, Daniel V.; Huie, Philip; Vankov, Alexander B.; Freyvert, Yev; Fishman, Harvey; Marmor, Michael F.; Blumenkranz, Mark S.

    2004-07-01

    Development of the electronic retinal prosthesis for restoration of sight in patients suffering from the degenerative retinal diseases faces many technological challenges. To achieve significant improvement in the low vision patients the visual acuity of 20/80 would be desirable, which corresponds to the pixel size of 20μm in the retinal implant. Stimulating current strongly (quadratically) depends on distance between electrode and cell. To achieve uniformity in stimulation thresholds, to avoid erosion of the electrodes and overheating of tissue, and to reduce the cross-talk between the neighboring pixels the neural cells should not be separated from electrodes by more than a few micrometers. Achieving such a close proximity along the whole surface of an implant is one of the major obstacles for the high resolution retinal implant. To ensure proximity of cells and electrodes we have developed a technique that prompts migration of retinal cells towards stimulating sites. The device consists of a multilayered membrane with an array of perforations of several (5-15) micrometers in diameter in which addressable electrodes can be embedded. In experiments in-vitro using explants of the whole retina of P7 rats, and in-vivo using adult rabbits and RCS rats the retinal tissue grew into the pores when membranes were positioned on the sub-retinal side. Histology has demonstrated that migrating cells preserve synaptic connections with cells outside the pores, thus allowing for signal transduction into the retina above the implant. Intimate proximity of cells to electrodes achieved with this technique allows for reduction of the stimulation current to 2μA at the 10μm electrode. A 3mm disk array with 18,000 pixels can stimulate cells with 0.5 ms pulses at 50Hz while maintaining temperature rise at the implant surface below 0.3°C. Such an implant can, in principle, provide spatial resolution geometrically corresponding to the visual acuity of 20/80 in a visual field of 10°.

  19. Access resistance of stimulation electrodes as a function of electrode proximity to the retina

    NASA Astrophysics Data System (ADS)

    Majdi, Joseph A.; Minnikanti, Saugandhika; Peixoto, Nathalia; Agrawal, Anant; Cohen, Ethan D.

    2015-02-01

    Objective. Epiretinal prostheses seek to effectively stimulate the retina by positioning electrode arrays close to its surface so current pulses generate narrow retinal electric fields. Our objective was to evaluate the use of the electrical impedance of insulated platinum electrodes as a measure of the proximity of insulated platinum electrodes to the inner surface of the retina. Approach. We examined the impedance of platinum disk electrodes, 0.25 mm in diameter, insulated with two widths (0.8 and 1.6 mm outer diameter) of transparent fluoropolymer in a rabbit retinal eyecup preparation. Optical coherence tomography measured the electrode’s proximity to the retinal surface which was correlated with changes in the voltage waveform at the electrode. Electrode impedance changes during retinal deformation were also studied. Main results. When the 1.6 mm diameter insulated electrodes advanced towards the retinal surface from 1000 μm, their voltage step at current pulse onset increased, reflecting an access resistance increase of 3880 ± 630 Ω, with the 50% midpoint averaging 30 μm, while thin 0.8 mm insulated electrode advancement showed an access resistance increase 50% midpoint averaging 16 μm. Using impedance spectroscopy, electrode-retina proximity differences were seen in the 1.6 mm insulated electrode impedance modulus between 1 and 100 kHz and the waveform phase angle at 0.3-10 kHz, while thin 0.8 mm insulated electrode advancement produced smaller impedance modulus changes with retinal proximity between 3 and 100 kHz. These impedance changes with retinal proximity may reflect different sized zones of eye wall being coupled in series with the insulated platinum electrode. Significance. The proximity of stimulus electrodes to neural tissue in fluid-filled spaces can be estimated from access resistance changes in the stimulus pulse waveform. Because many prosthetic devices allow back telemetry communication of the stimulus electrode waveform, it is possible

  20. Performance of conducting polymer electrodes for stimulating neuroprosthetics

    NASA Astrophysics Data System (ADS)

    Green, R. A.; Matteucci, P. B.; Hassarati, R. T.; Giraud, B.; Dodds, C. W. D.; Chen, S.; Byrnes-Preston, P. J.; Suaning, G. J.; Poole-Warren, L. A.; Lovell, N. H.

    2013-02-01

    Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

  1. Implantable optical-electrode device for stimulation of spinal motoneurons

    NASA Astrophysics Data System (ADS)

    Matveev, M. V.; Erofeev, A. I.; Zakharova, O. A.; Pyatyshev, E. N.; Kazakin, A. N.; Vlasova, O. L.

    2016-08-01

    Recent years, optogenetic method of scientific research has proved its effectiveness in the nerve cell stimulation tasks. In our article we demonstrate an implanted device for the spinal optogenetic motoneurons activation. This work is carried out in the Laboratory of Molecular Neurodegeneration of the Peter the Great St. Petersburg Polytechnic University, together with Nano and Microsystem Technology Laboratory. The work of the developed device is based on the principle of combining fiber optic light stimulation of genetically modified cells with the microelectrode multichannel recording of neurons biopotentials. The paper presents a part of the electrode implant manufacturing technique, combined with the optical waveguide of ThorLabs (USA).

  2. Electrodeposited iridium oxide for neural stimulation and recording electrodes.

    PubMed

    Meyer, R D; Cogan, S F; Nguyen, T H; Rauh, R D

    2001-03-01

    Iridium oxide films formed by electrodeposition onto noniridium metal substrates are compared with activated iridium oxide films (AIROFs) as a low impedance, high charge capacity coating for neural stimulation and recording electrodes. The electrodeposited iridium oxide films (EIROFs) were deposited on Au, Pt, PtIr, and 316 LVM stainless steel substrates from a solution of IrCl4, oxalic acid, and K2CO3. A deposition protocol involving 50 potential sweeps at 50 mV/s between limits of 0.0 V and 0.55 V (versus Ag AgCl) followed by potential pulsing between the same limits produced adherent films with a charge storage capacity of >25 mC/cm2. Characterization by cyclic voltammetry and impedance spectroscopy revealed no differences in the electrochemical behavior of EIROF on non-Ir substrates and AIROF. The mechanical stability of the oxides was evaluated by ultrasonication in distilled water followed by dehydration and rehydration. Stability under charge injection was evaluated using 200 micros, 5.9 A/cm2 (1.2 mC/cm2) cathodal pulses. Loss of iridium oxide charge capacity was comparable for AIROFs and the EIROFs, ranging from 1% to 8% of the capacity immediately after activation or deposition. The EIROFs were deposited and evaluated on silicon microprobe electrodes and on metallized polyimide electrodes being developed for neural recording and stimulation applications.

  3. Sputtered iridium oxide films (SIROFs) for neural stimulation electrodes

    PubMed Central

    Cogan, Stuart F.; Ehrlich, Julia; Plante, Timothy D.; Smirnov, Anton; Shire, Douglas B.; Gingerich, Marcus; Rizzo, Joseph F.

    2009-01-01

    Sputtered iridium oxide films (SIROFs) deposited by DC reactive sputtering from an iridium metal target have been characterized in vitro for their potential as neural recording and stimulation electrodes. SIROFs were deposited over gold metallization on flexible multielectrode arrays fabricated on thin (15 µm) polyimide substrates. SIROF thickness and electrode areas of 200–1300 nm and 1960–125600 µm2, respectively, were investigated. The charge-injection capacities of the SIROFs were evaluated in an inorganic interstitial fluid model in response to charge-balanced, cathodal-first current pulses. Charge injection capacities were measured as a function of cathodal pulse width (0.2 – 1 ms) and potential bias in the interpulse period (0.0 to 0.7 V vs. Ag|AgCl). Depending on the pulse parameters and electrode area, charge-injection capacities ranged from 1–9 mC/cm2, comparable with activated iridium oxide films (AIROFs) pulsed under similar conditions. Other parameters relevant to the use of SIROF on nerve electrodes, including the thickness dependence of impedance (0.05–105 Hz) and the current necessary to maintain a bias in the interpulse region were also determined. PMID:17271216

  4. Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex

    NASA Astrophysics Data System (ADS)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2011-12-01

    Epidural electrical stimulation (ECS) of the motor cortex is a developing therapy for neurological disorders. Both placement and programming of ECS systems may affect the therapeutic outcome, but the treatment parameters that will maximize therapeutic outcomes and minimize side effects are not known. We delivered ECS to the motor cortex of anesthetized cats and investigated the effects of electrode placement and stimulation parameters on thresholds for evoking motor responses in the contralateral forelimb. Thresholds were inversely related to stimulation frequency and the number of pulses per stimulus train. Thresholds were lower over the forelimb representation in motor cortex (primary site) than surrounding sites (secondary sites), and thresholds at sites <4 mm away from the primary site were significantly lower than at sites >4 mm away. Electrode location and montage influenced the effects of polarity on thresholds: monopolar anodic and cathodic thresholds were not significantly different over the primary site, cathodic thresholds were significantly lower than anodic thresholds over secondary sites and bipolar thresholds were significantly lower with the anode over the primary site than with the cathode over the primary site. A majority of bipolar thresholds were either between or equal to the respective monopolar thresholds, but several bipolar thresholds were greater than or less than the monopolar thresholds of both the anode and cathode. During bipolar stimulation, thresholds were influenced by both electric field superposition and indirect, synaptically mediated interactions. These results demonstrate the influence of stimulation parameters and electrode location during cortical stimulation, and these effects should be considered during the programming of systems for therapeutic cortical stimulation.

  5. Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat.

    PubMed

    van der Plasse, Geoffrey; Schrama, Regina; van Seters, Sebastiaan P; Vanderschuren, Louk J M J; Westenberg, Herman G M

    2012-01-01

    Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa.

  6. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes; turning tables: should GPi become the preferred DBS target for Parkinson disease?

    PubMed

    Montgomery, Erwin B

    2013-01-08

    Weaver et al. and Tagliati mistakenly infer clinical equivalence between globus pallidus interna vs subthalamic nucleus deep brain stimulation based on failure to demonstrate statistically significant differences. A clinically meaningful-not statistically significant-difference in outcome should be decided a priori, after which the sample size necessary to have a reasonable probability of detecting the difference could be determined. (4) Fortunately, the study by Weaver et al. had sufficient sample size to demonstrate a 1-point difference in motor outcomes. However, such comparisons presume optimal management so as not to produce a "ceiling effect" that would obscure differences.

  7. The CMS DBS query language

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Valentin; Riley, Daniel; Afaq, Anzar; Sekhri, Vijay; Guo, Yuyi; Lueking, Lee

    2010-04-01

    The CMS experiment has implemented a flexible and powerful system enabling users to find data within the CMS physics data catalog. The Dataset Bookkeeping Service (DBS) comprises a database and the services used to store and access metadata related to CMS physics data. To this, we have added a generalized query system in addition to the existing web and programmatic interfaces to the DBS. This query system is based on a query language that hides the complexity of the underlying database structure by discovering the join conditions between database tables. This provides a way of querying the system that is simple and straightforward for CMS data managers and physicists to use without requiring knowledge of the database tables or keys. The DBS Query Language uses the ANTLR tool to build the input query parser and tokenizer, followed by a query builder that uses a graph representation of the DBS schema to construct the SQL query sent to underlying database. We will describe the design of the query system, provide details of the language components and overview of how this component fits into the overall data discovery system architecture.

  8. Using liquid metal alloy (EGaIn) to electrochemically enhance SS stimulation electrodes for biobotic applications.

    PubMed

    Latif, Tahmid; Fengyuan Gong; Dickey, Michael; Sichitiu, Mihail; Bozkurt, Alper

    2016-08-01

    Biobotics is an emerging and useful advent in the field of robotics which harnesses the mechanical power of live invertebrates and benefits from them as "working" animals. Most biobotic applications rely on neural or muscular stimulation through implanted electrodes for achieving direct control of their locomotory behavior. Degradation of stimulation efficiency is often noticed through extended usage, partly owing to incompatibility of implanted electrodes to the application. Our previous achievements in biobotics utilized commercially available stainless steel wires as stimulation electrodes due to its availability and lower cost. In this study, we look into the potential of using a liquid metal alloy, eutectic gallium-indium (EGaIn), as a means of enhancing properties of the stainless steel electrodes and its first time consideration as in vivo neurostimulation electrodes. We present in vitro analysis of the electrodes in terms of the electrolyte-electrode interface impedance and interface equivalent circuit model.

  9. Novel fingerprinting method characterises the necessary and sufficient structural connectivity from deep brain stimulation electrodes for a successful outcome

    NASA Astrophysics Data System (ADS)

    Fernandes, Henrique M.; Van Hartevelt, Tim J.; Boccard, Sandra G. J.; Owen, Sarah L. F.; Cabral, Joana; Deco, Gustavo; Green, Alex L.; Fitzgerald, James J.; Aziz, Tipu Z.; Kringelbach, Morten L.

    2015-01-01

    Deep brain stimulation (DBS) is a remarkably effective clinical tool, used primarily for movement disorders. DBS relies on precise targeting of specific brain regions to rebalance the oscillatory behaviour of whole-brain neural networks. Traditionally, DBS targeting has been based upon animal models (such as MPTP for Parkinson’s disease) but has also been the result of serendipity during human lesional neurosurgery. There are, however, no good animal models of psychiatric disorders such as depression and schizophrenia, and progress in this area has been slow. In this paper, we use advanced tractography combined with whole-brain anatomical parcellation to provide a rational foundation for identifying the connectivity ‘fingerprint’ of existing, successful DBS targets. This knowledge can then be used pre-surgically and even potentially for the discovery of novel targets. First, using data from our recent case series of cingulate DBS for patients with treatment-resistant chronic pain, we demonstrate how to identify the structural ‘fingerprints’ of existing successful and unsuccessful DBS targets in terms of their connectivity to other brain regions, as defined by the whole-brain anatomical parcellation. Second, we use a number of different strategies to identify the successful fingerprints of structural connectivity across four patients with successful outcomes compared with two patients with unsuccessful outcomes. This fingerprinting method can potentially be used pre-surgically to account for a patient’s individual connectivity and identify the best DBS target. Ultimately, our novel fingerprinting method could be combined with advanced whole-brain computational modelling of the spontaneous dynamics arising from the structural changes in disease, to provide new insights and potentially new targets for hitherto impenetrable neuropsychiatric disorders.

  10. A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

    PubMed Central

    Gong, Cihun-Siyong Alex; Lai, Hsin-Yi; Huang, Sy-Han; Lo, Yu-Chun; Lee, Nicole; Chen, Pin-Yuan; Tu, Po-Hsun; Yang, Chia-Yen; Lin, James Chang-Chieh; Chen, You-Yin

    2015-01-01

    Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design. PMID:26029954

  11. A programmable high-voltage compliance neural stimulator for deep brain stimulation in vivo.

    PubMed

    Gong, Cihun-Siyong Alex; Lai, Hsin-Yi; Huang, Sy-Han; Lo, Yu-Chun; Lee, Nicole; Chen, Pin-Yuan; Tu, Po-Hsun; Yang, Chia-Yen; Lin, James Chang-Chieh; Chen, You-Yin

    2015-05-28

    Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design.

  12. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

    PubMed

    Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

    2016-12-07

    Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory.

  13. Nano-Ampere Stimulation Window for Cultured Neurons on Micro-Electrode Arrays

    DTIC Science & Technology

    2001-10-25

    the electrical potential and σ the conductivity of the NANO -AMPÈRE STIMULATION WINDOW FOR CULTURED NEURONS ON MICRO -ELECTRODE ARRAYS J.R. Buitenweg1... Nano -Ampere Stimulatin Window for Cultured Neurons on Micro -Electrode Arrays Contract Number Grant Number Program Element Number Author(s) Project...membrane, using a nano -ampère current through the extracellular electrode. Also, a stimulation window is observed. These findings can be explained by a

  14. Masking patterns for monopolar and phantom electrode stimulation in cochlear implants

    PubMed Central

    Saoji, Aniket A.; Landsberger, David M.; Padilla, Monica; Litvak, Leonid M.

    2013-01-01

    Phantom electrode (PE) stimulation consists of out-of-phase stimulation of two electrodes. When presented at the apex of the electrode array, phantom stimulation is known to produce a lower pitch sensation than monopolar (MP) stimulation on the most apical electrode. The ratio of the current between the primary electrode (PEL) and the compensating electrode (CEL) is represented by the coefficient σ, which ranges from 0 (monopolar) to 1 (full bipolar). The exact mechanism by which PE stimulation produces a lower pitch sensation is unclear. In the present study, unmasked and masked thresholds were obtained using a forward masking paradigm to estimate the spread of current for MP and PE stimulation. Masked thresholds were measured for two phantom electrode configurations (1) PEL = 4, CEL = 5 (lower pitch phantom) and (2) PEL = 4, CEL = 3 (higher pitch phantom). The unmasked thresholds were subtracted from the masked thresholds to obtain masking patterns which were normalized to their peak. The masking patterns reveal (1) differences in the spread of excitation that are consistent with the direction of pitch shift produced by PE stimulation, and (2) narrower spread of electrical excitation for PE stimulation relative to MP stimulation. PMID:23299125

  15. Electroconductive polymer-coated silk fiber electrodes for neural recording and stimulation in vivo

    NASA Astrophysics Data System (ADS)

    Watanabe, Satoshi; Takahashi, Hideyuki; Torimitsu, Keiichi

    2017-03-01

    We fabricated a silk-based low-impedance flexible electrode by coating a silk thread with the electroconductive polymer poly(3,4-ethylenedioxythiophene) doped with p-toluenesulfonate (PEDOT:pTS). This electrode had a lower impedance (about 1.8 kΩ/cm) than the silk electrode coated with PEDOT doped with poly(styrene sulfonate) (PEDOT:PSS) (about 1.3 MΩ/cm) reported previously. Using this electrode, a novel gamma-band oscillatory activity was recorded in the electrocorticogram from the embryonic chick brain with a high signal-to-noise ratio. Electrical stimulation was also possible with the silk electrode. We also fabricated an all-silk electrode array and recorded synchronized gamma oscillations. These results demonstrate that the silk electrode can be used for electrophysiological recording and local stimulation in vivo. The silk electrode has the potential to be used for diagnostic and therapeutic purposes and as a brain–machine interface.

  16. Effects of deep brain stimulation and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson's disease.

    PubMed

    Vaillancourt, David E; Prodoehl, Janey; Sturman, Molly M; Bakay, Roy A E; Metman, Leo Verhagen; Corcos, Daniel M

    2006-01-01

    We investigated the control of movement in 12 patients with Parkinson's disease (PD) after they received surgically implanted high-frequency stimulating electrodes in the subthalamic nucleus (STN). The experiment studied ankle strength, movement velocity, and the associated electromyographic patterns in PD patients, six of whom had tremor at the ankle. The patients were studied off treatment, ON STN deep brain stimulation (DBS), on medication, and on medication plus STN DBS. Twelve matched control subjects were also examined. Medication alone and STN DBS alone increased patients' ankle strength, ankle velocity, agonist muscle burst amplitude, and agonist burst duration, while reducing the number of agonist bursts during movement. These findings were similar for PD patients with and without tremor. The combination of medication plus STN DBS normalized maximal strength at the ankle joint, but ankle movement velocity and electromyographic patterns were not normalized. The findings are the first to demonstrate that STN DBS and medication increase strength and movement velocity at the ankle joint.

  17. A Nerve Clamp Electrode Design for Indirect Stimulation of Skeletal Muscle

    DTIC Science & Technology

    2010-10-01

    Reports www.BioTechniques.com739Vol. 49 | No. 4 | 2010 Ex vivo assays to measure muscle paralysis induced by botulinum neurotoxin (BoNT) have been...Keywords: stimulating electrode; botulinum neurotoxin; skeletal muscle; paralysis A nerve clamp electrode was developed to indirectly stimulate skeletal...attached nerve. Indirect muscle stimulation is critical for studying the para- lytic actions of presynaptic-acting toxins such as botulinum neurotoxins

  18. A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina.

    PubMed

    Maturana, Matias I; Apollo, Nicholas V; Hadjinicolaou, Alex E; Garrett, David J; Cloherty, Shaun L; Kameneva, Tatiana; Grayden, David B; Ibbotson, Michael R; Meffin, Hamish

    2016-04-01

    Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron's electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy.

  19. A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina

    PubMed Central

    Maturana, Matias I.; Apollo, Nicholas V.; Hadjinicolaou, Alex E.; Garrett, David J.; Cloherty, Shaun L.; Kameneva, Tatiana; Grayden, David B.; Ibbotson, Michael R.; Meffin, Hamish

    2016-01-01

    Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron’s electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy. PMID:27035143

  20. PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities

    NASA Astrophysics Data System (ADS)

    Samba, R.; Herrmann, T.; Zeck, G.

    2015-02-01

    Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

  1. Construction of a simple suction electrode for extracellular recording and stimulation.

    PubMed

    Johnson, Bruce R; Hauptman, Stephen A; Bonow, Robert H

    2007-01-01

    Principles of signal transmission in nervous systems are commonly demonstrated in the undergraduate neuroscience laboratory through extracellular recording of nerve and muscle action potentials. Here we describe the construction of a simple suction electrode that we use routinely in our laboratory classes for nerve recording and stimulation. The electrode parts are relatively inexpensive, easily available from established scientific and electronic distributors and local hardware stores, and the electrode is resilient to student handling. Our undergraduate students use this electrode design for high resolution, extracellular recordings of action potentials from crayfish motor and sensory nerves and insect muscle, and for stimulation of crustacean and insect motor nerves.

  2. Local glutamate release in the rat ventral lateral thalamus evoked by high-frequency stimulation

    NASA Astrophysics Data System (ADS)

    Agnesi, Filippo; Blaha, Charles D.; Lin, Jessica; Lee, Kendall H.

    2010-04-01

    Thalamic deep brain stimulation (DBS) is proven therapy for essential tremor, Parkinson's disease and Tourette's syndrome. We tested the hypothesis that high-frequency electrical stimulation results in local thalamic glutamate release. Enzyme-linked glutamate amperometric biosensors were implanted in anesthetized rat thalamus adjacent to the stimulating electrode. Electrical stimulation was delivered to investigate the effect of frequency, pulse width, voltage-controlled or current-controlled stimulation, and charge balancing. Monophasic electrical stimulation-induced glutamate release was linearly dependent on stimulation frequency, intensity and pulse width. Prolonged stimulation evoked glutamate release to a plateau that subsequently decayed back to baseline after stimulation. Glutamate release was less pronounced with voltage-controlled stimulation and not present with charge balanced current-controlled stimulation. Using fixed potential amperometry in combination with a glutamate bioprobe and adjacent microstimulating electrode, the present study has shown that monophasic current-controlled stimulation of the thalamus in the anesthetized rat evoked linear increases in local extracellular glutamate concentrations that were dependent on stimulation duration, frequency, intensity and pulse width. However, the efficacy of monophasic voltage-controlled stimulation, in terms of evoking glutamate release in the thalamus, was substantially lower compared to monophasic current-controlled stimulation and entirely absent with biphasic (charge balanced) current-controlled stimulation. It remains to be determined whether similar glutamate release occurs with human DBS electrodes and similar charge balanced stimulation. As such, the present results indicate the importance of evaluating local neurotransmitter dynamics in studying the mechanism of action of DBS.

  3. Deep brain stimulation of the nucleus accumbens shell increases impulsive behavior and tissue levels of dopamine and serotonin.

    PubMed

    Sesia, Thibaut; Bulthuis, Vincent; Tan, Sonny; Lim, Lee Wei; Vlamings, Rinske; Blokland, Arjan; Steinbusch, Harry W M; Sharp, Trevor; Visser-Vandewalle, Veerle; Temel, Yasin

    2010-10-01

    The nucleus accumbens (NAc) is gaining interest as a target for deep brain stimulation (DBS) in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. In animal models, it has been shown that DBS of the NAc changes impulsive action. Here, we tested the hypothesis that a change in impulsive action by DBS of the NAc is associated with changes in dopamine levels. Rats received stimulating electrodes either in the NAc core or shell, and underwent behavioral testing in a reaction time task. In addition, in a second experiment, the effect of DBS of the NAc core and shell on extracellular dopamine and serotonin levels was assessed in the NAc and medial prefrontal cortex. Control subjects received sham surgery. We have found that DBS of the NAc shell stimulation induced more impulsive action but less perseverative checking. These effects were associated with increased levels of dopamine and serotonin in the NAc, but not in the medial prefrontal cortex. DBS of the NAc core had no effect on impulsive action, but decreased perseverative responses indicative of a better impulse control. In these subjects, no effects were found on neurotransmitter levels. Our data point out that DBS of the NAc shell has negative effects on impulsive action which is accompanied by increases of dopamine and serotonin levels in the NAc, whereas DBS of the NAc core has beneficial behavioral effects.

  4. Methods for Specific Electrode Resistance Measurement during Transcranial Direct Current Stimulation

    PubMed Central

    Khadka, Niranjan; Rahman, Asif; Sarantos, Chris; Truong, Dennis Q.; Bikson, Marom

    2014-01-01

    Background Transcranial Direct Current Stimulation (tDCS) is investigated to treat a wide range of neuropsychiatric disorders, for rehabilitation, and for enhancing cognitive performance. The monitoring of electrode resistance before and during tDCS is considered important for tolerability and safety, where an unusually high resistance is indicative of undesired electrode or poor skin contact conditions. Conventional resistance measurement methods do not isolate individual electrode resistance but rather measures overall voltage. Moreover, for HD-tDCS devices, cross talk across electrodes makes concurrent resistance monitoring unreliable. Objective We propose a novel method for monitoring of the individual electrode resistance during tDCS, using a super-position of direct current with a test-signal (low-intensity and low-frequency sinusoids with electrode– specific frequencies) and a single sentinel electrode (not used for DC). Methods To validate this methodology, we developed lumped-parameter models of two and multi-electrode tDCS. Approaches with and without a sentinel electrode were solved and underlying assumptions identified. Assumptions were tested and parameterized in healthy participants using forearm stimulation combining tDCS (2 mA) and sinusoidal test-signals (38 μA and 76 μA peak to peak at 1 Hz, 10 Hz, and 100 Hz) and an in vitro test (where varied electrode failure modes were created). DC and AC component voltages across the electrodes were compared and participants were asked to rate subjective pain. Results A sentinel electrode is required to isolate electrode resistance in a two-electrode tDCS system. For multi-electrode resistance tracking, cross talk was aggravated with electrode proximity and current/resistance mismatches, but could be corrected using proposed approaches. Average voltage and average pain scores were not significantly different across test current intensities and frequencies (two-way repeated measures ANOVA) indicating the

  5. A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR).

    PubMed

    Sudhyadhom, Atchar; Haq, Ihtsham U; Foote, Kelly D; Okun, Michael S; Bova, Frank J

    2009-08-01

    DBS depends on precise placement of the stimulating electrode into an appropriate target region. Image-based (direct) targeting has been limited by the ability of current technology to visualize DBS targets. We have recently developed and employed a Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) 3T MRI sequence to more reliably visualize these structures. The FGATIR provides significantly better high resolution thin (1 mm) slice visualization of DBS targets than does either standard 3T T1 or T2-weighted imaging. The T1 subcortical image revealed relatively poor contrast among the targets for DBS, though the sequence did allow localization of striatum and thalamus. T2 FLAIR scans demonstrated better contrast between the STN, SNr, red nucleus (RN), and pallidum (GPe/GPi). The FGATIR scans allowed for localization of the thalamus, striatum, GPe/GPi, RN, and SNr and displayed sharper delineation of these structures. The FGATIR also revealed features not visible on other scan types: the internal lamina of the GPi, fiber bundles from the internal capsule piercing the striatum, and the boundaries of the STN. We hope that use of the FGATIR to aid initial targeting will translate in future studies to faster and more accurate procedures with consequent improvements in clinical outcomes.

  6. Probabilistic Analysis of Activation Volumes Generated During Deep Brain Stimulation

    PubMed Central

    Butson, Christopher R.; Cooper, Scott E.; Henderson, Jaimie M.; Wolgamuth, Barbara; McIntyre, Cameron C.

    2010-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson’s disease (PD) and shows great promise for the treatment of several other disorders. However, while the clinical analysis of DBS has received great attention, a relative paucity of quantitative techniques exists to define the optimal surgical target and most effective stimulation protocol for a given disorder. In this study we describe a methodology that represents an evolutionary addition to the concept of a probabilistic brain atlas, which we call a probabilistic stimulation atlas (PSA). We outline steps to combine quantitative clinical outcome measures with advanced computational models of DBS to identify regions where stimulation-induced activation could provide the best therapeutic improvement on a per-symptom basis. While this methodology is relevant to any form of DBS, we present example results from subthalamic nucleus (STN) DBS for PD. We constructed patient-specific computer models of the volume of tissue activated (VTA) for 163 different stimulation parameter settings which were tested in six patients. We then assigned clinical outcome scores to each VTA and compiled all of the VTAs into a PSA to identify stimulation-induced activation targets that maximized therapeutic response with minimal side effects. The results suggest that selection of both electrode placement and clinical stimulation parameter settings could be tailored to the patient’s primary symptoms using patient-specific models and PSAs. PMID:20974269

  7. Probabilistic analysis of activation volumes generated during deep brain stimulation.

    PubMed

    Butson, Christopher R; Cooper, Scott E; Henderson, Jaimie M; Wolgamuth, Barbara; McIntyre, Cameron C

    2011-02-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD) and shows great promise for the treatment of several other disorders. However, while the clinical analysis of DBS has received great attention, a relative paucity of quantitative techniques exists to define the optimal surgical target and most effective stimulation protocol for a given disorder. In this study we describe a methodology that represents an evolutionary addition to the concept of a probabilistic brain atlas, which we call a probabilistic stimulation atlas (PSA). We outline steps to combine quantitative clinical outcome measures with advanced computational models of DBS to identify regions where stimulation-induced activation could provide the best therapeutic improvement on a per-symptom basis. While this methodology is relevant to any form of DBS, we present example results from subthalamic nucleus (STN) DBS for PD. We constructed patient-specific computer models of the volume of tissue activated (VTA) for 163 different stimulation parameter settings which were tested in six patients. We then assigned clinical outcome scores to each VTA and compiled all of the VTAs into a PSA to identify stimulation-induced activation targets that maximized therapeutic response with minimal side effects. The results suggest that selection of both electrode placement and clinical stimulation parameter settings could be tailored to the patient's primary symptoms using patient-specific models and PSAs.

  8. Electrical stimulation with a penetrating optic nerve electrode array elicits visuotopic cortical responses in cats

    NASA Astrophysics Data System (ADS)

    Lu, Yiliang; Yan, Yan; Chai, Xinyu; Ren, Qiushi; Chen, Yao; Li, Liming

    2013-06-01

    Objective. A visual prosthesis based on penetrating electrode stimulation within the optic nerve (ON) is a potential way to restore partial functional vision for blind patients. We investigated the retinotopic organization of ON stimulation and its spatial resolution. Approach. A five-electrode array was inserted perpendicularly into the ON or a single electrode was advanced to different depths within the ON (˜1-2 mm behind the eyeball, 13 cats). A sparse noise method was used to map ON electrode position and the visual cortex. Cortical responses were recorded by a 5 × 6 array. The visuotopic correspondence between the retinotopic position of the ON electrode was compared with the visual evoked cortical map and the electrical evoked potentials elicited in response to ON stimulation. Main results. Electrical stimulation with penetrating ON electrodes elicited cortical responses in visuotopographically corresponding areas of the cortex. Stimulation of the temporal side of the ON elicited cortical responses corresponding to the central visual field. The visual field position shifted from the lower to central visual field as the electrode penetrated through the depth of the ON. A spatial resolution of ˜ 2° to 3° within a limited cortical visuotopic representation could be obtained by this approach. Significance. Visuotopic electrical stimulation with a relatively fine spatial resolution can be accomplished using penetrating electrodes implanted at multiple sites and at different depths within the ON just behind the globe. This study also provides useful experimental data for the design of electrode density and the distribution of penetrating ON electrodes for a visual prosthesis.

  9. Activation of retinal ganglion cells following epiretinal electrical stimulation with hexagonally arranged bipolar electrodes

    NASA Astrophysics Data System (ADS)

    Abramian, Miganoosh; Lovell, Nigel H.; Morley, John W.; Suaning, Gregg J.; Dokos, Socrates

    2011-06-01

    We investigated retinal ganglion cell (RGC) responses to epiretinal electrical stimulation delivered by hexagonally arranged bipolar (Hex) electrodes, in order to assess the feasibility of this electrode arrangement for future retinal implant devices. In vitro experiments were performed using rabbit retinal preparations, with results compared to a computational model of axonal stimulation. Single-unit RGC responses to electrical stimulation were recorded with extracellular microelectrodes. With 100 µs/phase biphasic pulses, the threshold charge densities were 24.0 ± 11.2 and 7.7 ± 3.2 µC cm-2 for 50 and 125 µm diameter Hex electrodes, respectively. Threshold profiles and response characteristics strongly suggested that RGC axons were the neural activation site. Both the model and in vitro data indicated that localized tissue stimulation is achieved with Hex electrodes.

  10. Tip surface changes in endocardial stimulation electrode, visualised by scanning electron microscopy.

    PubMed

    Hladky, M; Horn, V; Kamaryt, P; Cabanova, J; Zeman, K

    1975-01-01

    The authors have been probably the first investigators who applied scanning electron microscopy to studies of the changes occurring in the surface of the metalic tip of an endocardial stimulating electrode. They found a lowered conductivity for secondary electron emission, and describe the surface changes in a platiniridium-tipped electrode which had been used for almost four years, in comparison with an unused electrode.

  11. Dynamic Impedance Model of the Skin-Electrode Interface for Transcutaneous Electrical Stimulation

    PubMed Central

    Vargas Luna, José Luis; Krenn, Matthias; Cortés Ramírez, Jorge Armando; Mayr, Winfried

    2015-01-01

    Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes. PMID:25942010

  12. Electrochemical properties of titanium nitride nerve stimulation electrodes: an in vitro and in vivo study

    PubMed Central

    Meijs, Suzan; Fjorback, Morten; Jensen, Carina; Sørensen, Søren; Rechendorff, Kristian; Rijkhoff, Nico J. M.

    2015-01-01

    The in vivo electrochemical behavior of titanium nitride (TiN) nerve stimulation electrodes was compared to their in vitro behavior for a period of 90 days. Ten electrodes were implanted in two Göttingen minipigs. Four of these were used for electrical stimulation and electrochemical measurements. Five electrodes were kept in Ringer's solution at 37.5°C, of which four were used for electrical stimulation and electrochemical measurements. The voltage transients measured in vivo were 13 times greater than in vitro at implantation and they continued to increase with time. The electrochemical properties in vivo and the tissue resistance (Rtissue) followed a similar trend with time. There was no consistent significant difference between the electrochemical properties of the in vivo and in vitro electrodes after the implanted period. The differences between the in vivo and in vitro electrodes during the implanted period show that the evaluation of electrochemical performance of implantable stimulation electrodes cannot be substituted with in vitro measurements. After the implanted period, however, the performance of the in vivo and in vitro electrodes in saline was similar. In addition, the changes observed over time during the post-implantation period regarding the electrochemical properties of the in vivo electrodes and Rtissue were similar, which indicates that these changes are due to the foreign body response to implantation. PMID:26300717

  13. Electrochemical properties of titanium nitride nerve stimulation electrodes: an in vitro and in vivo study.

    PubMed

    Meijs, Suzan; Fjorback, Morten; Jensen, Carina; Sørensen, Søren; Rechendorff, Kristian; Rijkhoff, Nico J M

    2015-01-01

    The in vivo electrochemical behavior of titanium nitride (TiN) nerve stimulation electrodes was compared to their in vitro behavior for a period of 90 days. Ten electrodes were implanted in two Göttingen minipigs. Four of these were used for electrical stimulation and electrochemical measurements. Five electrodes were kept in Ringer's solution at 37.5°C, of which four were used for electrical stimulation and electrochemical measurements. The voltage transients measured in vivo were 13 times greater than in vitro at implantation and they continued to increase with time. The electrochemical properties in vivo and the tissue resistance (Rtissue) followed a similar trend with time. There was no consistent significant difference between the electrochemical properties of the in vivo and in vitro electrodes after the implanted period. The differences between the in vivo and in vitro electrodes during the implanted period show that the evaluation of electrochemical performance of implantable stimulation electrodes cannot be substituted with in vitro measurements. After the implanted period, however, the performance of the in vivo and in vitro electrodes in saline was similar. In addition, the changes observed over time during the post-implantation period regarding the electrochemical properties of the in vivo electrodes and Rtissue were similar, which indicates that these changes are due to the foreign body response to implantation.

  14. The role of electrode location and stimulation polarity in patient response to cortical stimulation for Major Depressive Disorder

    PubMed Central

    Pathak, Yagna; Kopell, Brian H.; Szabo, Aniko; Rainey, Charles; Harsch, Harold; Butson, Christopher R.

    2015-01-01

    Background Major Depressive Disorder (MDD) is a neuropsychiatric condition that affects about one-sixth of the US population. Chronic epidural stimulation (EpCS) of the left dorsolateral prefrontal cortex (DLPFC) was recently evaluated as a treatment option for refractory MDD and was found to be effective during the open-label phase. However, two potential sources of variability in the study were differences in electrode position and the range of stimulation modes that were used in each patient. The objective of this study was to examine these factors in an effort to characterize successful EpCS therapy. Methods Data were analyzed from eleven patients who received EpCS via a chronically implanted system. Estimates were generated of response probability as a function of duration of stimulation. The relative effectiveness of different stimulation modes was also evaluated. Lastly, a computational analysis of the pre- and post-operative imaging was performed to assess the effects of electrode location. The primary outcome measure was the change in Hamilton Depression Rating Scale (HDRS-28). Results Significant improvement was observed in mixed mode stimulation (alternating cathodic and anodic) and continuous anodic stimulation (full power). The changes observed in HDRS-28 over time suggest that 20 weeks of stimulation are necessary to approach a 50% response probability. Lastly, stimulation in the lateral and anterior regions of DLPFC was correlated with greatest degree of improvement. Conclusions A persistent problem in neuromodulation studies has been the selection of stimulation parameters and electrode location to provide optimal therapeutic response. The approach used in this paper suggests that insights can be gained by performing a detailed analysis of response while controlling for important details such as electrode location and stimulation settings. PMID:22819247

  15. Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode

    PubMed Central

    MacEwan, Matthew R.; Zellmer, Erik R.; Wheeler, Jesse J.; Burton, Harold; Moran, Daniel W.

    2016-01-01

    Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation. PMID:28008303

  16. Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode.

    PubMed

    MacEwan, Matthew R; Zellmer, Erik R; Wheeler, Jesse J; Burton, Harold; Moran, Daniel W

    2016-01-01

    Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm(2) surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.

  17. Electrical Stimulation of Mammalian Retinal Ganglion Cells Using Dense Arrays of Small-Diameter Electrodes

    NASA Astrophysics Data System (ADS)

    Sekirnjak, Chris; Hottowy, Pawel; Sher, Alexander; Dabrowski, Wladyslaw; Litke, Alan M.; Chichilnisky, E. J.

    Current epiretinal implants contain a small number of electrodes with diameters of a few hundred microns. Smaller electrodes are desirable to increase the spatial resolution of artificial sight. To lay the foundation for the next generation of retinal prostheses, we assessed the stimulation efficacy of micro-fabricated arrays of 61 platinum disk electrodes with diameters 8-12 μm, spaced 60 μm apart. Isolated pieces of rat, guinea pig, and monkey retina were placed on the multi-electrode array ganglion cell side down and stimulated through individual electrodes with biphasic, charge-balanced current pulses. Spike responses from retinal ganglion cells were recorded either from the same or a neighboring electrode. Most pulses evoked only 1-2 spikes with short latencies (0.3-10 ms), and rarely was more than one recorded ganglion cell stimulated. Threshold charge densities for eliciting spikes in ganglion cells were typically below 0.15 mC/cm2 for pulse durations between 50 and 200 μs, corresponding to charge thresholds of ˜ 100 pC. Stimulation remained effective after several hours and at frequencies up to 100 Hz. Application of cadmium chloride did not abolish evoked spikes, implying direct activation. Thus, electrical stimulation of mammalian retina with small-diameter electrodes is achievable, providing high temporal and spatial precision with low charge densities.

  18. Model-based analysis of multiple electrode array stimulation for epiretinal visual prostheses

    NASA Astrophysics Data System (ADS)

    Mueller, Jerel K.; Grill, Warren M.

    2013-06-01

    Objective. Epiretinal stimulation, which uses an array of electrodes implanted on the inner retinal surface to relay a representation of the visual scene to the neuronal elements of the retina, has seen considerable success. The objective of the present study was to quantify the effects of multi-electrode stimulation on the patterns of neural excitation in a computational model of epiretinal stimulation. Approach. A computational model of retinal ganglion cells was modified to represent the morphology of human retinal ganglion cells and validated against published experimental data. The ganglion cell model was then combined with a model of an axon of the nerve fiber layer to produce a population model of the inner retina. The response of the population of model neurons to epiretinal stimulation with a multi-electrode array was quantified across a range of electrode geometries using a novel means to quantify the model response—the minimum radius circle bounding the activated model neurons as a proxy for the evoked phosphene. Main results. Multi-electrode stimulation created unique phosphenes, such that the number of potential phosphenes can far exceed the number of electrode contacts. Significance. The ability to exploit the spatial and temporal interactions of stimulation may be critical to improvements in the performance of epiretinal prostheses.

  19. Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder.

    PubMed

    Neumann, W-J; Huebl, J; Brücke, C; Gabriëls, L; Bajbouj, M; Merkl, A; Schneider, G-H; Nuttin, B; Brown, P; Kühn, A A

    2014-11-01

    The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD.

  20. Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis.

    PubMed

    Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

    2014-01-01

    Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis.

  1. Development of a Flexible Non-Metal Electrode for Cell Stimulation and Recording

    PubMed Central

    Gong, Cihun-Siyong Alex; Syu, Wun-Jia; Lei, Kin Fong; Hwang, Yih-Shiou

    2016-01-01

    This study presents a method of producing flexible electrodes for potentially simultaneously stimulating and measuring cellular signals in retinal cells. Currently, most multi-electrode applications rely primarily on etching, but the metals involved have a certain degree of brittleness, leaving them prone to cracking under prolonged pressure. This study proposes using silver chloride ink as a conductive metal, and polydimethysiloxane (PDMS) as the substrate to provide electrodes with an increased degree of flexibility to allow them to bend. This structure is divided into the electrode layer made of PDMS and silver chloride ink, and a PDMS film coating layer. PDMS can be mixed in different proportions to modify the degree of rigidity. The proposed method involved three steps. The first segment entailed the manufacturing of the electrode, using silver chloride ink as the conductive material, and using computer software to define the electrode size and micro-engraving mechanisms to produce the electrode pattern. The resulting uniform PDMS pattern was then baked onto the model, and the flow channel was filled with the conductive material before air drying to produce the required electrode. In the second stage, we tested the electrode, using an impedance analyzer to measure electrode cyclic voltammetry and impedance. In the third phase, mechanical and biocompatibility tests were conducted to determine electrode properties. This study aims to produce a flexible, non-metallic sensing electrode which fits snugly for use in a range of measurement applications. PMID:27690049

  2. Enhancement of Fear Extinction with Deep Brain Stimulation: Evidence for Medial Orbitofrontal Involvement

    PubMed Central

    Rodriguez-Romaguera, Jose; Do-Monte, Fabricio H; Tanimura, Yoko; Quirk, Gregory J; Haber, Suzanne N

    2015-01-01

    Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces anxiety, fear, and compulsive symptoms in patients suffering from refractory obsessive-compulsive disorder. In a rodent model, DBS-like high-frequency stimulation of VS can either enhance or impair extinction of conditioned fear, depending on the location of electrodes within VS (dorsal vs ventral). As striatal DBS activates fibers descending from the cortex, we reasoned that the differing effects on extinction may reflect differences in cortical sources of fibers passing through dorsal–VS and ventral–VS. In agreement with prior anatomical studies, we found that infralimbic (IL) and anterior insular (AI) cortices project densely through ventral–VS, the site where DBS impaired extinction. Contrary to IL and AI, we found that medial orbitofrontal cortex (mOFC) projects densely through dorsal–VS, the site where DBS enhanced extinction. Furthermore, pharmacological inactivation of mOFC reduced conditioned fear and DBS of dorsal-VS-induced plasticity (pERK) in mOFC neurons. Our results support the idea that VS DBS modulates fear extinction by stimulating specific fibers descending from mOFC and prefrontal cortices. PMID:25601229

  3. Deep brain stimulation for movement and other neurologic disorders.

    PubMed

    DeLong, Mahlon; Wichmann, Thomas

    2012-08-01

    Deep brain stimulation (DBS) was introduced as a treatment for patients with parkinsonism and other movement disorders in the early 1990s. The technique rapidly became the treatment of choice for these conditions, and is now also being explored for other diseases, including Tourette syndrome, gait disorders, epilepsy, obsessive-compulsive disorder, and depression. Although the mechanism of action of DBS remains unclear, it is recognized that DBS works through focal modulation of functionally specific circuits. The fact that the same DBS parameters and targets can be used in multiple diseases suggests that DBS does not counteract the pathophysiology of any specific disorder, but acts to replace pathologic activities in disease-affected brain circuits with activity that is more easily tolerated. Despite the progress made in the use of DBS, much remains to be done to fully realize the potential of this therapy. We describe some of the most active areas of research in this field, both in terms of exploration of new targets and stimulation parameters, and in terms of new electrode or stimulator designs.

  4. Orientation selective deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom

    2017-02-01

    Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

  5. Effects of DBS in parkinsonian patients depend on the structural integrity of frontal cortex

    PubMed Central

    Muthuraman, Muthuraman; Deuschl, Günther; Koirala, Nabin; Riedel, Christian; Volkmann, Jens; Groppa, Sergiu

    2017-01-01

    While deep brain stimulation of the subthalamic nucleus (STN-DBS) has evolved to an evidence-based standard treatment for Parkinson’s disease (PD), the targeted cerebral networks are poorly described and no objective predictors for the postoperative clinical response exist. To elucidate the systemic mechanisms of DBS, we analysed cerebral grey matter properties using cortical thickness measurements and addressed the dependence of structural integrity on clinical outcome. Thirty one patients with idiopathic PD without dementia (23 males, age: 63.4 ± 9.3, Hoehn and Yahr: 3.5 ± 0.8) were selected for DBS treatment. The patients underwent whole-brain preoperative T1 MR-Imaging at 3 T. Grey matter integrity was assessed by cortical thickness measurements with FreeSurfer. The clinical motor outcome markedly improved after STN-DBS in comparison to the preoperative condition. The cortical thickness of the frontal lobe (paracentral area and superior frontal region) predicted the clinical improvement after STN-DBS. Moreover, in patients with cortical atrophy of these areas a higher stimulation voltage was needed for an optimal clinical response. Our data suggest that the effects of STN-DBS in PD directly depend on frontal lobe grey matter integrity. Cortical atrophy of this region might represent a distinct predictor of a poor motor outcome after STN-DBS in PD patients. PMID:28262813

  6. Particle swarm optimization for programming deep brain stimulation arrays

    NASA Astrophysics Data System (ADS)

    Peña, Edgar; Zhang, Simeng; Deyo, Steve; Xiao, YiZi; Johnson, Matthew D.

    2017-02-01

    Objective. Deep brain stimulation (DBS) therapy relies on both precise neurosurgical targeting and systematic optimization of stimulation settings to achieve beneficial clinical outcomes. One recent advance to improve targeting is the development of DBS arrays (DBSAs) with electrodes segmented both along and around the DBS lead. However, increasing the number of independent electrodes creates the logistical challenge of optimizing stimulation parameters efficiently. Approach. Solving such complex problems with multiple solutions and objectives is well known to occur in biology, in which complex collective behaviors emerge out of swarms of individual organisms engaged in learning through social interactions. Here, we developed a particle swarm optimization (PSO) algorithm to program DBSAs using a swarm of individual particles representing electrode configurations and stimulation amplitudes. Using a finite element model of motor thalamic DBS, we demonstrate how the PSO algorithm can efficiently optimize a multi-objective function that maximizes predictions of axonal activation in regions of interest (ROI, cerebellar-receiving area of motor thalamus), minimizes predictions of axonal activation in regions of avoidance (ROA, somatosensory thalamus), and minimizes power consumption. Main results. The algorithm solved the multi-objective problem by producing a Pareto front. ROI and ROA activation predictions were consistent across swarms (<1% median discrepancy in axon activation). The algorithm was able to accommodate for (1) lead displacement (1 mm) with relatively small ROI (⩽9.2%) and ROA (⩽1%) activation changes, irrespective of shift direction; (2) reduction in maximum per-electrode current (by 50% and 80%) with ROI activation decreasing by 5.6% and 16%, respectively; and (3) disabling electrodes (n  =  3 and 12) with ROI activation reduction by 1.8% and 14%, respectively. Additionally, comparison between PSO predictions and multi-compartment axon

  7. Computational modeling of pedunculopontine nucleus deep brain stimulation

    PubMed Central

    Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

    2013-01-01

    Objective Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson’s disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models, and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results The computational models predicted that: 1) the majority of PPN neurons are activated with −3V monopolar cathodic stimulation; 2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; 3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3V); 4) monopolar stimulation in rostral, lateral, or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at −3V); and, 5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS. PMID:23723145

  8. Computational modeling of pedunculopontine nucleus deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

    2013-08-01

    Objective. Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson's disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach. Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results. The computational models predicted that: (1) the majority of PPN neurons are activated with -3 V monopolar cathodic stimulation; (2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; (3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3 V) (4) monopolar stimulation in rostral, lateral or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at -3 V) and (5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance. We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.

  9. Brain Stimulation Therapies

    MedlinePlus

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  10. An energy-efficient, adiabatic electrode stimulator with inductive energy recycling and feedback current regulation.

    PubMed

    Arfin, Scott K; Sarpeshkar, Rahul

    2012-02-01

    In this paper, we present a novel energy-efficient electrode stimulator. Our stimulator uses inductive storage and recycling of energy in a dynamic power supply. This supply drives an electrode in an adiabatic fashion such that energy consumption is minimized. It also utilizes a shunt current-sensor to monitor and regulate the current through the electrode via feedback, thus enabling flexible and safe stimulation. Since there are no explicit current sources or current limiters, wasteful energy dissipation across such elements is naturally avoided. The dynamic power supply allows efficient transfer of energy both to and from the electrode and is based on a DC-DC converter topology that we use in a bidirectional fashion in forward-buck or reverse-boost modes. In an exemplary electrode implementation intended for neural stimulation, we show how the stimulator combines the efficiency of voltage control and the safety and accuracy of current control in a single low-power integrated-circuit built in a standard .35 μm CMOS process. This stimulator achieves a 2x-3x reduction in energy consumption as compared to a conventional current-source-based stimulator operating from a fixed power supply. We perform a theoretical analysis of the energy efficiency that is in accord with experimental measurements. This theoretical analysis reveals that further improvements in energy efficiency may be achievable with better implementations in the future. Our electrode stimulator could be widely useful for neural, cardiac, retinal, cochlear, muscular and other biomedical implants where low power operation is important.

  11. Immediate motor effects of stimulation through electrodes implanted in the human globus pallidus.

    PubMed

    Ashby, P; Strafella, A; Dostrovsky, J O; Lozano, A; Lang, A E

    1998-01-01

    The immediate motor effects of stimulation through electrodes chronically implanted in the globus pallidus internus (GPI) were studied in 9 subjects with Parkinson's disease. Single stimuli (at >0.4 Hz) produced short latency facilitation of voluntarily activated contralateral muscles in all subjects. The latency and distribution of the facilitation, its probably monosynaptic nature, and the short chronaxie and refractory period of the activated neural elements suggest that the facilitation results from the direct excitation of the fast conducting corticospinal pathway. The facilitation of motoneurons followed high frequency (e.g. 200 Hz) stimulation without decrement and occurred at stimulus intensities well below those required to produce a visible muscle contraction. We conclude that, while there may be other effects, GPI stimulation through electrodes may activate the corticospinal tract, even when the stimuli are below the threshold for a visible muscle contraction, and that continuous stimulation may do so continuously. This may be an unwanted side effect, but possible therapeutic actions are considered. The reproducible short latency facilitation enabled us to estimate current spread from the quadripolar electrodes used for deep brain stimulation. When the current is sufficient to excite large myelinated fibers near one of the quadripolar electrodes, an additional 1-mA current will activate similar fibers at an additional distance of 1.8 mm with bipolar stimulation and at a distance of 5.7 mm with monopolar stimulation.

  12. Evaluation of novel stimulus waveforms for deep brain stimulation

    PubMed Central

    Foutz, TJ; McIntyre, CC

    2010-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of a wide range of neurological disorders. Historically, DBS and other neurostimulation technologies have relied on rectangular stimulation waveforms to impose their effects on the nervous system. Recent work has suggested that non-rectangular waveforms may have advantages over the traditional rectangular pulse. Therefore, we used detailed computer models to compare a range of charge-balanced biphasic waveforms with rectangular, exponential, triangular, Gaussian, and sinusoidal stimulus pulse shapes. We explored the neural activation energy of these waveforms in both intracellular and extracellular stimulation. In the context of extracellular stimulation, we compared their effects on both axonal fibers of passage and projection neurons. Finally, we evaluated the impact of delivering the waveforms through a clinical DBS electrode, as opposed to a theoretical point source. Our results suggest that DBS with a 1 ms centered-triangular pulse can decrease energy consumption by 64 % when compared to the standard 100 μs rectangular pulse (energy cost of 48 nJ and 133 nJ, respectively, to stimulate 50 % of a distributed population of axons) and can decrease energy consumption by 10 % when compared to the most energy efficient rectangular pulse (1.25 ms duration). In turn, there may be measureable energy savings when using appropriately designed non-rectangular pulses in clinical DBS applications, thereby warranting further experimental investigation. PMID:21084732

  13. Evaluation of novel stimulus waveforms for deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Foutz, Thomas J.; McIntyre, Cameron C.

    2010-12-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of a wide range of neurological disorders. Historically, DBS and other neurostimulation technologies have relied on rectangular stimulation waveforms to impose their effects on the nervous system. Recent work has suggested that non-rectangular waveforms may have advantages over the traditional rectangular pulse. Therefore, we used detailed computer models to compare a range of charge-balanced biphasic waveforms with rectangular, exponential, triangular, Gaussian and sinusoidal stimulus pulse shapes. We explored the neural activation energy of these waveforms for both intracellular and extracellular current-controlled stimulation conditions. In the context of extracellular stimulation, we compared their effects on both axonal fibers of passage and projection neurons. Finally, we evaluated the impact of delivering the waveforms through a clinical DBS electrode, as opposed to a theoretical point source. Our results suggest that DBS with a 1 ms centered-triangular pulse can decrease energy consumption by 64% when compared with the standard 100 µs rectangular pulse (energy cost of 48 and 133 nJ, respectively, to stimulate 50% of a distributed population of axons) and can decrease energy consumption by 10% when compared with the most energy efficient rectangular pulse (1.25 ms duration). In turn, there may be measureable energy savings when using appropriately designed non-rectangular pulses in clinical DBS applications, thereby warranting further experimental investigation.

  14. Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.

    PubMed

    Melega, William P; Lacan, Goran; Gorgulho, Alessandra A; Behnke, Eric J; De Salles, Antonio A F

    2012-01-01

    Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.

  15. Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model

    PubMed Central

    Melega, William P.; Lacan, Goran; Gorgulho, Alessandra A.; Behnke, Eric J.; De Salles, Antonio A. F.

    2012-01-01

    Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight. PMID:22295102

  16. Quasi-Monopolar Stimulation: A Novel Electrode Design Configuration for Performance Optimization of a Retinal Neuroprosthesis

    PubMed Central

    Khalili Moghadam, Gita; Wilke, Robert; Suaning, Gregg J.; Lovell, Nigel H.; Dokos, Socrates

    2013-01-01

    In retinal neuroprostheses, spatial interaction between electric fields from various electrodes – electric crosstalk – may occur in multielectrode arrays during simultaneous stimulation of the retina. Depending on the electrode design and placement, this crosstalk can either enhance or degrade the functional characteristics of a visual prosthesis. To optimize the device performance, a balance must be satisfied between the constructive interference of crosstalk on dynamic range and power consumption and its negative effect on artificial visual acuity. In the present computational modeling study, we have examined the trade-off in these positive and negative effects using a range of currently available electrode array configurations, compared to a recently proposed stimulation strategy – the quasi monopolar (QMP) configuration – in which the return current is shared between local bipolar guards and a distant monopolar electrode. We evaluate the performance of the QMP configuration with respect to the implantation site and electrode geometry parameters. Our simulation results demonstrate that the beneficial effects of QMP are only significant at electrode-to-cell distances greater than the electrode dimensions. Possessing a relatively lower activation threshold, QMP was found to be superior to the bipolar configuration in terms of providing a relatively higher visual acuity. However, the threshold for QMP was more sensitive to the topological location of the electrode in the array, which may need to be considered when programming the manner in which electrode are simultaneously activated. This drawback can be offset with a wider dynamic range and lower power consumption of QMP. Furthermore, the ratio of monopolar return current to total return can be used to adjust the functional performance of QMP for a given implantation site and electrode parameters. We conclude that the QMP configuration can be used to improve visual information-to-stimulation mapping in a

  17. Corrosion of glassy carbon neural electrodes under electrical stimulation and chemical exposure

    NASA Astrophysics Data System (ADS)

    Gong, Nick Thomas

    Advances in research of neural prosthetics have led to the development of novel materials used for neural stimulation applications. Glassy carbon (GC) has demonstrated promise as a novel and robust material that can be used in such applications. This study focused on reporting the in-vitro testing of GC microelectrodes under stimulation and chemical exposure to simulate an in-vivo environment, and to determine corrosion. Microelectrode arrays were fabricated and tested for an electrochemical (EC) setup for long-term corrosion tests. GC electrode pillars were used to test the testing apparatus, and confirm its ability to stimulate the GC microelectrodes. Electrode stimulation was conducted over 7 and 14 day time periods in phosphate buffer saline (PBS) with two different types of hydrogen peroxide (H2O2), USP and ACS. Corrosion of GC neural microelectrode arrays was monitored by physical, chemical, and electrochemical characterization methods. GC corrosion was characterized and evaluated over the duration of this study. Both GC and platinum microelectrode arrays were subjected to the same parameters. USP H2O2 did not corrode GC electrodes and characterization revealed that a protective layer can be preventing further electrode degradation. ACS H2O2 corroded GC electrodes. Implications of this work have given insights and new directions on testing neural prosthetic microelectrode arrays for stimulation applications.

  18. High spatial resolution single multiwalled carbon nanotube electrode for stimulation, recording, and whole cell voltage clamping of electrically active cells

    NASA Astrophysics Data System (ADS)

    de Asis, Edward D.; Leung, Joseph; Wood, Sally; Nguyen, Cattien V.

    2009-10-01

    We report the stimulation, recording, and voltage clamp of muscle fibers using a 30 nm diameter single multiwalled carbon nanotube electrode (sMWNT electrode) tip. Because of the lower access resistance, the sMWNT electrode conducts extracellular and intracellular stimulation more efficiently compared to glass micropipettes. The sMWNT electrode records field potentials and action potentials and performs whole cell voltage clamping of single fibers.

  19. Automated 3-Dimensional Brain Atlas Fitting to Microelectrode Recordings from Deep Brain Stimulation Surgeries

    PubMed Central

    Luján, J. Luis; Noecker, Angela M.; Butson, Christopher R.; Cooper, Scott E.; Walter, Benjamin L.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2009-01-01

    Objective Deep brain stimulation (DBS) surgeries commonly rely on brain atlases and microelectrode recordings (MER) to help identify the target location for electrode implantation. We present an automated method for optimally fitting a 3-dimensional brain atlas to intraoperative MER and predicting a target DBS electrode location in stereotactic coordinates for the patient. Methods We retrospectively fit a 3-dimensional brain atlas to MER points from 10 DBS surgeries targeting the subthalamic nucleus (STN). We used a constrained optimization algorithm to maximize the MER points correctly fitted (i.e., contained) within the appropriate atlas nuclei. We compared our optimization approach to conventional anterior commissure-posterior commissure (AC/PC) scaling, and to manual fits performed by four experts. A theoretical DBS electrode target location in the dorsal STN was customized to each patient as part of the fitting process and compared to the location of the clinically defined therapeutic stimulation contact. Results The human expert and computer optimization fits achieved significantly better fits than the AC/PC scaling (80, 81, and 41% of correctly fitted MER, respectively). However, the optimization fits were performed in less time than the expert fits and converged to a single solution for each patient, eliminating interexpert variance. Conclusions and Significance DBS therapeutic outcomes are directly related to electrode implantation accuracy. Our automated fitting techniques may aid in the surgical decision-making process by optimally integrating brain atlas and intraoperative neurophysiological data to provide a visual guide for target identification. PMID:19556832

  20. A Study on Cross-Talk Nerve Stimulation: Electrode Placement and Current Leakage Lid

    PubMed Central

    Julémont, Nicolas; Nonclercq, Antoine; Delchambre, Alain; Vanhoestenberghe, Anne

    2016-01-01

    Cross-talk phenomena should be avoided when stimulating nerves. One option to limit the current spread is to use tripolar electrodes, but at the cost of increasing the number of wires connection. This should be avoided since cables must be thin and compliant. We investigated the impact of the central electrode position and of current spread due to a gap between book and lid on cross-talk, in a set of tripolar or quasi-tripolar configurations.. PMID:27990238

  1. Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study

    PubMed Central

    Baradaran‐Shoraka, Massoud; Reynolds, Brent A.; Okun, Michael S.

    2016-01-01

    Objectives Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up‐regulation of neural progenitor cell proliferation in post‐mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia. Methods We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells. Results We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p = 0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p = 0.0013, MCM2; p = 0.0002). Interpretation We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions. PMID:27018335

  2. Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus.

    PubMed

    Lentz, Linnea; Zhao, Yan; Kelly, Matthew T; Schindeldecker, William; Goetz, Steven; Nelson, Dwight E; Raike, Robert S

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia.

  3. Multi-electrode stimulation in somatosensory cortex increases probability of detection

    NASA Astrophysics Data System (ADS)

    Zaaimi, Boubker; Ruiz-Torres, Ricardo; Solla, Sara A.; Miller, Lee E.

    2013-10-01

    Objective. Brain machine interfaces (BMIs) that decode control signals from motor cortex have developed tremendously in the past decade, but virtually all rely exclusively on vision to provide feedback. There is now increasing interest in developing an afferent interface to replace natural somatosensation, much as the cochlear implant has done for the sense of hearing. Preliminary experiments toward a somatosensory neuroprosthesis have mostly addressed the sense of touch, but proprioception, the sense of limb position and movement, is also critical for the control of movement. However, proprioceptive areas of cortex lack the precise somatotopy of tactile areas. We showed previously that there is only a weak tendency for neighboring neurons in area 2 to signal similar directions of hand movement. Consequently, stimulation with the relatively large currents used in many studies is likely to activate a rather heterogeneous set of neurons. Approach. Here, we have compared the effect of single-electrode stimulation at subthreshold levels to the effect of stimulating as many as seven electrodes in combination. Main results. We found a mean enhancement in the sensitivity to the stimulus (d‧) of 0.17 for pairs compared to individual electrodes (an increase of roughly 30%), and an increase of 2.5 for groups of seven electrodes (260%). Significance. We propose that a proprioceptive interface made up of several hundred electrodes may yield safer, more effective sensation than a BMI using fewer electrodes and larger currents.

  4. A Lithographically-Patterned, Elastic Multi-electrode Array for Surface Stimulation of the Spinal Cord

    PubMed Central

    Meacham, Kathleen W.; Giuly, Richard J.; Guo, Liang; Hochman, Shawn; DeWeerth, Stephen P.

    2008-01-01

    A new, scalable process for microfabrication of a silicone-based, elastic multi-electrode array (MEA) is presented. The device is constructed by spinning poly(dimethylsiloxane) (PDMS) silicone elastomer onto a glass slide, depositing and patterning gold to construct wires and electrodes, spinning on a second PDMS layer, and then micropatterning the second PDMS layer to expose electrode contacts. The micropatterning of PDMS involves a custom reactive ion etch (RIE) process that preserves the underlying gold thin film. Once completed, the device can be removed from the glass slide for conformal interfacing with neural tissue. Prototype MEAs feature electrodes smaller than those known to be reported on silicone substrate (60 μm diameter exposed electrode area) and were capable of selectively stimulating the surface of the in vitro isolated spinal cord of the juvenile rat. Stretchable serpentine traces were also incorporated into the functional PDMS-based MEA, and their implementation and testing is described. PMID:17914674

  5. Intensity coding in electric hearing: Effects of electrode configurations and stimulation waveforms

    PubMed Central

    Chua, Tiffany Elise H.; Bachman, Mark; Zeng, Fan-Gang

    2011-01-01

    Objectives Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception, but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. Design The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were 5 Clarion cochlear implant users. For each subject, data from apical, middle and basal electrode positions were collected when possible. Results Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. Conclusions The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings, nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen. PMID:21610498

  6. Dependence of Dbl and Dbs Transformation on MEK and NF-κB Activation

    PubMed Central

    Whitehead, Ian P.; Lambert, Que T.; Glaven, Judith A.; Abe, Karon; Rossman, Kent L.; Mahon, Gwendolyn M.; Trzaskos, James M.; Kay, Robert; Campbell, Sharon L.; Der, Channing J.

    1999-01-01

    Dbs was identified initially as a transforming protein and is a member of the Dbl family of proteins (>20 mammalian members). Here we show that Dbs, like its rat homolog Ost and the closely related Dbl, exhibited guanine nucleotide exchange activity for the Rho family members RhoA and Cdc42, but not Rac1, in vitro. Dbs transforming activity was blocked by specific inhibitors of RhoA and Cdc42 function, demonstrating the importance of these small GTPases in Dbs-mediated growth deregulation. Although Dbs transformation was dependent upon the structural integrity of its pleckstrin homology (PH) domain, replacement of the PH domain with a membrane localization signal restored transforming activity. Thus, the PH domain of Dbs (but not Dbl) may be important in modulating association with the plasma membrane, where its GTPase substrates reside. Both Dbs and Dbl activate multiple signaling pathways that include activation of the Elk-1, Jun, and NF-κB transcription factors and stimulation of transcription from the cyclin D1 promoter. We found that Elk-1 and NF-κB, but not Jun, activation was necessary for Dbl and Dbs transformation. Finally, we have observed that Dbl and Dbs regulated transcription from the cyclin D1 promoter in a NF-κB-dependent manner. Previous studies have dissociated actin cytoskeletal activity from the transforming potential of RhoA and Cdc42. These observations, when taken together with those of the present study, suggest that altered gene expression, and not actin reorganization, is the critical mediator of Dbl and Rho family protein transformation. PMID:10523665

  7. Investigation of DBS electro-oxidation reaction in the aqueous-organic solution of LiClO4.

    PubMed

    Darlewski, Witold; Popiel, Stanisław; Nalepa, Tomasz; Gromotowicz, Waldemar; Szewczyk, Rafał; Stankiewicz, Romuald

    2010-03-15

    A process of dibutyl sulphide (DBS) electro-oxidation using electrolysis and cyclic voltamperometry was investigated in water-methanol solution using different electrodes (platinum, boron doped diamond, graphite and glassy carbon). Obtained results indicate that the DBS electro-oxidation process is irreversible in voltamperometric conditions. It was shown that during DBS electrolytic oxidation on Pt, at the low anode potential (1.8 V), DBS was oxidized to sulphoxide and sulphone. Electrolysis at higher potential (up to 3.0 V) resulted in complete DBS oxidation and formation of various products, including: butyric acid, sulphuric acid, butanesulphinic acid, butanesulphonic acid, identified using gas chromatography (GC-AED) and mass spectrometry (GC-MS) methods.

  8. A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

    PubMed

    Grahn, Peter J; Mallory, Grant W; Khurram, Obaid U; Berry, B Michael; Hachmann, Jan T; Bieber, Allan J; Bennet, Kevin E; Min, Hoon-Ki; Chang, Su-Youne; Lee, Kendall H; Lujan, J L

    2014-01-01

    Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.

  9. A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies

    PubMed Central

    Grahn, Peter J.; Mallory, Grant W.; Khurram, Obaid U.; Berry, B. Michael; Hachmann, Jan T.; Bieber, Allan J.; Bennet, Kevin E.; Min, Hoon-Ki; Chang, Su-Youne; Lee, Kendall H.; Lujan, J. L.

    2014-01-01

    Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a “smart” neuroprosthetic system for treatment of neurologic and psychiatric disorders

  10. Sulfonated polyaniline-based organic electrodes for controlled electrical stimulation of human osteosarcoma cells.

    PubMed

    Min, Yong; Yang, Yanyin; Poojari, Yadagiri; Liu, Yidong; Wu, Jen-Chieh; Hansford, Derek J; Epstein, Arthur J

    2013-06-10

    Electrically conducting polymers (CPs) were found to stimulate various cell types such as neurons, osteoblasts, and fibroblasts in both in vitro and in vivo studies. However, to our knowledge, no studies have been reported on the utility of CPs in stimulation of cancer or tumor cells in the literature. Here we report a facile fabrication method of self-doped sulfonated polyaniline (SPAN)-based interdigitated electrodes (IDEs) for controlled electrical stimulation of human osteosarcoma (HOS) cells. Increased degree of sulfonation was found to increase the SPAN conductivity, which in turn improved the cell attachment and cell growth without electrical stimulation. However, an enhanced cell growth was observed under controlled electrical (AC) stimulation at low applied voltage and frequency (≤800 mV and ≤1 kHz). The cell growth reached a maximum threshold at an applied voltage or frequency and beyond which pronounced cell death was observed. We believe that these organic electrodes may find utility in electrical stimulation of cancer or tumor cells for therapy and research and may also provide an alternative to the conventional metal-based electrodes.

  11. Vertical electric field stimulation of neural cells on porous amorphous carbon electrodes

    NASA Astrophysics Data System (ADS)

    Jain, Shilpee; Sharma, Ashutosh; Basu, Bikramjit

    2014-03-01

    We demonstrate the efficacy of amorphous macroporous carbon substrates as electrodes to stimulate neuronal cell proliferation in presence of external electric field. The electric field was applied perpendicular to carbon electrode, while growing mouse neuroblastoma (N2a) cells in vitro. The placement of the second electrode outside of the cell culture medium allows the investigation of cell response to electric field without the concurrent complexities of submerged electrodes such as potentially toxic electrode reactions, electro-kinetic flows and charge transfer (electrical current) in the cell medium. The macroporous carbon electrodes are uniquely characterized by a higher specific charge storage capacity (0.2 mC/cm2) and low impedance (3.3 k Ω at 1 kHz). When a uniform or a gradient electric field was applied perpendicular to the amorphous carbon substrate, it was found that the N2a cell viability and neurite length were higher at low electric field strengths (<= 2.5 V/cm) compared to that measured without an applied field (0 V/cm). Overall, the results of the present study unambiguously establish the uniform/gradient vertical electric field based culture protocol to stimulate neurite outgrowth and viability of nerve cells.

  12. Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of "Smart" Deep Brain Stimulation

    NASA Technical Reports Server (NTRS)

    Koehne, Jessica E.

    2016-01-01

    A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

  13. Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of Smart Deep Brain Stimulation

    NASA Technical Reports Server (NTRS)

    Koehne, Jessica E.

    2016-01-01

    A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable "smart" therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

  14. Patterns of reoccurrence of segmental dystonia after discontinuation of deep brain stimulation

    PubMed Central

    Grips, E; Blahak, C; Capelle, H H; Bäzner, H; Weigel, R; Sedlaczek, O; Krauss, J K; Wöhrle, J C

    2007-01-01

    The pattern of reoccurrence of symptoms after discontinuation of deep brain stimulation (DBS) has not been systematically studied in dystonia. Eight patients (mean age (SD) 53.8 (14.4) years) with segmental dystonia at a mean follow‐up of 11.3 (4.2) months were studied after implantation of bilateral DBS electrodes in the internal globus pallidus using a standard video protocol and clinical rating scales, immediately and at 2 and 4 h after switching off DBS. Dystonic signs returned sequentially, with a rapid worsening of phasic and a slower worsening of tonic dystonic components. In all patients, phasic dystonic features appeared within a few minutes, whereas the tonic elements of dystonia reoccurred with a more variable delay. Differential clinical effects when withdrawing DBS might reflect its influence on different pathophysiological mechanisms in dystonia. PMID:17030588

  15. Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact

    NASA Astrophysics Data System (ADS)

    Kent, A. R.; Grill, W. M.

    2012-06-01

    The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use

  16. Predicting the effects of deep brain stimulation with diffusion tensor based electric field models.

    PubMed

    Butson, Christopher R; Cooper, Scott E; Henderson, Jaimie M; McIntyre, Cameron C

    2006-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of movement disorders, and has shown promising results for the treatment of a wide range of other neurological disorders. However, little is known about the mechanism of action of DBS or the volume of brain tissue affected by stimulation. We have developed methods that use anatomical and diffusion tensor MRI (DTI) data to predict the volume of tissue activated (VTA) during DBS. We co-register the imaging data with detailed finite element models of the brain and stimulating electrode to enable anatomically and electrically accurate predictions of the spread of stimulation. One critical component of the model is the DTI tensor field that is used to represent the 3-dimensionally anisotropic and inhomogeneous tissue conductivity. With this system we are able to fuse structural and functional information to study a relevant clinical problem: DBS of the subthalamic nucleus for the treatment of Parkinsons disease (PD). Our results show that inclusion of the tensor field in our model caused significant differences in the size and shape of the VTA when compared to a homogeneous, isotropic tissue volume. The magnitude of these differences was proportional to the stimulation voltage. Our model predictions are validated by comparing spread of predicted activation to observed effects of oculomotor nerve stimulation in a PD patient. In turn, the 3D tissue electrical properties of the brain play an important role in regulating the spread of neural activation generated by DBS.

  17. Deep brain stimulation of different pedunculopontine targets in a novel rodent model of parkinsonism.

    PubMed

    Gut, Nadine K; Winn, Philip

    2015-03-25

    The pedunculopontine tegmental nucleus (PPTg) has been proposed as a target for deep brain stimulation (DBS) in parkinsonian patients, particularly for symptoms such as gait and postural difficulties refractory to dopaminergic treatments. Several patients have had electrodes implanted aimed at the PPTg, but outcomes have been disappointing, with little evidence that gait and posture are improved. The PPTg is a heterogeneous structure. Consequently, exact target sites in PPTg, possible DBS mechanisms, and potential benefits still need systematic investigation in good animal models. We have investigated the role of PPTg in gait, developed a refined model of parkinsonism including partial loss of the PPTg with bilateral destruction of nigrostriatal dopamine neurons that mimics human pathophysiology, and investigated the effect of DBS at different PPTg locations on gait and posture using a wireless device that lets rats move freely while receiving stimulation. Neither partial nor complete lesions of PPTg caused gait deficits, underlining questions raised previously about the status of PPTg as a motor control structure. The effect of DBS in the refined and standard model of parkinsonism were very different despite minimal behavioral differences in nonstimulation control conditions. Anterior PPTg DBS caused severe episodes of freezing and worsened gait, whereas specific gait parameters were mildly improved by stimulation of posterior PPTg. These results emphasize the critical importance of intra-PPTg DBS location and highlight the need to take PPTg degeneration into consideration when modeling parkinsonian symptoms. They also further implicate a role for PPTg in the pathophysiology of parkinsonism.

  18. Artificial neural network based characterization of the volume of tissue activated during deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Chaturvedi, Ashutosh; Luján, J. Luis; McIntyre, Cameron C.

    2013-10-01

    Objective. Clinical deep brain stimulation (DBS) systems can be programmed with thousands of different stimulation parameter combinations (e.g. electrode contact(s), voltage, pulse width, frequency). Our goal was to develop novel computational tools to characterize the effects of stimulation parameter adjustment for DBS. Approach. The volume of tissue activated (VTA) represents a metric used to estimate the spatial extent of DBS for a given parameter setting. Traditional methods for calculating the VTA rely on activation function (AF)-based approaches and tend to overestimate the neural response when stimulation is applied through multiple electrode contacts. Therefore, we created a new method for VTA calculation that relied on artificial neural networks (ANNs). Main results. The ANN-based predictor provides more accurate descriptions of the spatial spread of activation compared to AF-based approaches for monopolar stimulation. In addition, the ANN was able to accurately estimate the VTA in response to multi-contact electrode configurations. Significance. The ANN-based approach may represent a useful method for fast computation of the VTA in situations with limited computational resources, such as a clinical DBS programming application on a tablet computer.

  19. Effects of Anterior Thalamic Nucleus Deep Brain Stimulation in Chronic Epileptic Rats

    PubMed Central

    Amorim, Beatriz; Cavarsan, Clarissa; Miranda, Maisa Ferreira; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Nobrega, José N.; Mello, Luiz E.; Hamani, Clement

    2014-01-01

    Deep brain stimulation (DBS) has been investigated for the treatment of epilepsy. In rodents, an increase in the latency for the development of seizures and status epilepticus (SE) has been reported in different animal models but the consequences of delivering stimulation to chronic epileptic animals have not been extensively addressed. We study the effects of anterior thalamic nucleus (AN) stimulation at different current intensities in rats rendered epileptic following pilocarpine (Pilo) administration. Four months after Pilo-induced SE, chronic epileptic rats were bilaterally implanted with AN electrodes or had sham-surgery. Stimulation was delivered for 6 h/day, 5 days/week at 130 Hz, 90 µsec. and either 100 µA or 500 µA. The frequency of spontaneous recurrent seizures in animals receiving stimulation was compared to that recorded in the preoperative period and in rats given sham treatment. To investigate the effects of DBS on hippocampal excitability, brain slices from animals receiving AN DBS or sham surgery were studied with electrophysiology. We found that rats treated with AN DBS at 100 µA had a 52% non-significant reduction in the frequency of seizures as compared to sham-treated controls and 61% less seizures than at baseline. Animals given DBS at 500 µA had 5.1 times more seizures than controls and a 2.8 fold increase in seizure rate as compared to preoperative values. In non-stimulated controls, the average frequency of seizures before and after surgery remained unaltered. In vitro recordings have shown that slices from animals previously given DBS at 100 µA had a longer latency for the development of epileptiform activity, shorter and smaller DC shifts, and a smaller spike amplitude compared to non-stimulated controls. In contrast, a higher spike amplitude was recorded in slices from animals given AN DBS at 500 µA. PMID:24892420

  20. Intracranial electrode implantation produces regional neuroinflammation and memory deficits in rats

    SciTech Connect

    Kuttner-Hirshler, Y.; Biegon, A.; Kuttner-Hirshler, Y.; Polat, U.; Biegon, A.

    2009-12-21

    Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD). The procedure entails intracranial implantation of an electrode in a specific brain structure followed by chronic stimulation. Although the beneficial effects of DBS on motor symptoms in PD are well known, it is often accompanied by cognitive impairments, the origin of which is not fully understood. To explore the possible contribution of the surgical procedure itself, we studied the effect of electrode implantation in the subthalamic nucleus (STN) on regional neuroinflammation and memory function in rats implanted bilaterally with stainless steel electrodes. Age-matched sham and intact rats were used as controls. Brains were removed 1 or 8 weeks post-implantation and processed for in vitro autoradiography with [(3)H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and 2 and 8 weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at 1 as well as 8 weeks post-implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance 2 and 8 weeks post-implantation. Thus, electrode implantation resulted in a widespread and persistent neuroinflammation and sustained memory impairment. These results suggest that the insertion and continued presence of electrodes in the brain, even without stimulation, may lead to inflammation-mediated cognitive deficits in susceptible individuals, as observed in patients treated with DBS.

  1. Cochlear Implant Electrode Effect on Sound Energy Transfer within the Cochlea during Acoustic Stimulation

    PubMed Central

    Greene, Nathaniel T.; Mattingly, Jameson K.; Jenkins, Herman A.; Tollin, Daniel J.; Easter, James R.; Cass, Stephen P.

    2015-01-01

    Hypothesis Cochlear implants (CI) designed for hearing preservation will not alter mechanical properties of the middle and inner ear as measured by intracochlear pressure (PIC) and stapes velocity (Vstap). Background CIs designed to provide combined electrical and acoustic stimulation (EAS) are now available. To maintain functional acoustic hearing, it is important to know if a CI electrode can alter middle or inner ear mechanics, as any alteration could contribute to elevated low-frequency thresholds in EAS patients. Methods Seven human cadaveric temporal bones were prepared, and pure-tone stimuli from 120Hz–10kHz were presented at a range of intensities up to 110 dB SPL. PIC in the scala vestibuli (PSV) and tympani (PST) were measured with fiber-optic pressure sensors concurrently with VStap using laser Doppler vibrometry. Five CI electrodes from two different manufacturers, with varying dimensions were inserted via a round window approach at six different depths (16–25 mm). Results The responses of PIC and VStap to acoustic stimulation were assessed as a function of stimulus frequency, normalized to SPL in the external auditory canal (EAC), in baseline and electrode inserted conditions. Responses measured with electrodes inserted were generally within ~5 dB of baseline, indicating little effect of cochlear implant electrode insertion on PIC and VStap. Overall, mean differences across conditions were small for all responses, and no substantial differences were consistently visible across electrode types. Conclusions Results suggest that the influence of a CI electrode on middle and inner ear mechanics is minimal, despite variation in electrode lengths and configurations. PMID:26333018

  2. Patient-specific models of deep brain stimulation: Influence of field model complexity on neural activation predictions

    PubMed Central

    Chaturvedi, Ashutosh; Butson, Christopher R.; Lempka, Scott F.; Cooper, Scott E.; McIntyre, Cameron C.

    2010-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for medically intractable Parkinson’s disease. However, quantitative understanding of the interaction between the electric field generated by DBS and the underlying neural tissue is limited. Recently, computational models of varying levels of complexity have been used to study the neural response to DBS. The goal of this study was to evaluate the quantitative impact of incrementally incorporating increasing levels of complexity into computer models of STN DBS. Our analysis focused on the direct activation of experimentally measureable fiber pathways within the internal capsule (IC). Our model system was customized to an STN DBS patient and stimulation thresholds for activation of IC axons were calculated with electric field models that ranged from an electrostatic, homogenous, isotropic model to one that explicitly incorporated the voltage-drop and capacitance of the electrode-electrolyte interface, tissue encapsulation of the electrode, and diffusion-tensor based 3D tissue anisotropy and inhomogeneity. The model predictions were compared to experimental IC activation defined from electromyographic (EMG) recordings from eight different muscle groups in the contralateral arm and leg of the STN DBS patient. Coupled evaluation of the model and experimental data showed that the most realistic predictions of axonal thresholds were achieved with the most detailed model. Furthermore, the more simplistic neurostimulation models substantially overestimated the spatial extent of neural activation. PMID:20607090

  3. Patient-specific models of deep brain stimulation: influence of field model complexity on neural activation predictions.

    PubMed

    Chaturvedi, Ashutosh; Butson, Christopher R; Lempka, Scott F; Cooper, Scott E; McIntyre, Cameron C

    2010-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for medically intractable Parkinson's disease. However, quantitative understanding of the interaction between the electric field generated by DBS and the underlying neural tissue is limited. Recently, computational models of varying levels of complexity have been used to study the neural response to DBS. The goal of this study was to evaluate the quantitative impact of incrementally incorporating increasing levels of complexity into computer models of STN DBS. Our analysis focused on the direct activation of experimentally measureable fiber pathways within the internal capsule (IC). Our model system was customized to an STN DBS patient and stimulation thresholds for activation of IC axons were calculated with electric field models that ranged from an electrostatic, homogenous, isotropic model to one that explicitly incorporated the voltage-drop and capacitance of the electrode-electrolyte interface, tissue encapsulation of the electrode, and diffusion-tensor based 3D tissue anisotropy and inhomogeneity. The model predictions were compared to experimental IC activation defined from electromyographic (EMG) recordings from eight different muscle groups in the contralateral arm and leg of the STN DBS patient. Coupled evaluation of the model and experimental data showed that the most realistic predictions of axonal thresholds were achieved with the most detailed model. Furthermore, the more simplistic neurostimulation models substantially overestimated the spatial extent of neural activation.

  4. Controlling Bursting in Cortical Cultures with Closed-Loop Multi-Electrode Stimulation

    PubMed Central

    Wagenaar, Daniel A.; Madhavan, Radhika; Pine, Jerome; Potter, Steve M.

    2009-01-01

    One of the major modes of activity of high-density cultures of dissociated neurons is globally synchronized bursting. Unlike in vivo, neuronal ensembles in culture maintain activity patterns dominated by global bursts for the lifetime of the culture (up to 2 years). We hypothesize that persistence of bursting is caused by a lack of input from other brain areas. To study this hypothesis, we grew small but dense monolayer cultures of cortical neurons and glia from rat embryos on multi-electrode arrays and used electrical stimulation to substitute for afferents. We quantified the burstiness of the firing of the cultures in spontaneous activity and during several stimulation protocols. Although slow stimulation through individual electrodes increased burstiness as a result of burst entrainment, rapid stimulation reduced burstiness. Distributing stimuli across several electrodes, as well as continuously fine-tuning stimulus strength with closed-loop feedback, greatly enhanced burst control. We conclude that externally applied electrical stimulation can substitute for natural inputs to cortical neuronal ensembles in transforming burst-dominated activity to dispersed spiking, more reminiscent of the awake cortex in vivo. This nonpharmacological method of controlling bursts will be a critical tool for exploring the information processing capacities of neuronal ensembles in vitro and has potential applications for the treatment of epilepsy. PMID:15659605

  5. Modulation of cortical motor evoked potential after stroke during electrical stimulation of the lateral cerebellar nucleus

    PubMed Central

    Park, Hyun-Joo; Furmaga, Havan; Cooperrider, Jessica; Gale, John T.; Baker, Kenneth B.; Machado, Andre G.

    2015-01-01

    Background Deep brain stimulation (DBS) targeting the dentato-thalamo-cortical (DTC) pathway at its origin in the lateral cerebellar nucleus (LCN) has been shown to enhance motor recovery in a rodent model of cortical ischemia. LCN DBS also yielded frequency specific changes in motor cortex excitability in the normal brain, indexed by motor evoked potential (MEP) amplitude. Objective To investigate the effect of cortical stroke on cortical motor excitability in a rodent ischemia model and to measure the effects of LCN DBS on post-ischemia excitability as a function of stimulation parameters. Methods Adult Sprague-Dawley rats were divided into two groups: naïve and stroke, with cortical ischemia induced through multiple, unilateral endothelin-1 injections. All animals were implanted with a bipolar electrode in the LCN opposite the affected hemisphere. MEPs were elicited from the affected hemisphere using intracortical microstimulation (ICMS) techniques. Multiple LCN DBS parameters were examined, including isochronal stimulation at 20, 30, 50, and 100 Hz as well as a novel burst stimulation pattern. Results ICMS-evoked MEPs were reduced in stroke (n=10) relative to naïve (n=12) animals. However, both groups showed frequency-dependent augmentation of cortical excitability in response to LCN DBS. In the naïve group, LCN DBS increased MEPs by 22–58%, while in the stroke group, MEPs were enhanced by 9–41% compared to OFF DBS conditions. Conclusions Activation of the DTC pathway increases cortical excitability in both naïve and post-stroke animals. These effects may underlie, at least partially, functional reorganization and therapeutic benefits associated with chronic LCN DBS in post-stroke animals. PMID:26215752

  6. Deep brain stimulation of the subthalamic nucleus increases premature responding in a rat gambling task.

    PubMed

    Aleksandrova, Lily R; Creed, Meaghan C; Fletcher, Paul J; Lobo, Daniela S S; Hamani, Clement; Nobrega, José N

    2013-05-15

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n=24) or sham surgery (n=24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions.

  7. Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor

    NASA Astrophysics Data System (ADS)

    Keane, Maureen; Deyo, Steve; Abosch, Aviva; Bajwa, Jawad A.; Johnson, Matthew D.

    2012-08-01

    Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.

  8. A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain

    PubMed Central

    Bennet, Kevin E.; Tomshine, Jonathan R.; Min, Hoon-Ki; Manciu, Felicia S.; Marsh, Michael P.; Paek, Seungleal B.; Settell, Megan L.; Nicolai, Evan N.; Blaha, Charles D.; Kouzani, Abbas Z.; Chang, Su-Youne; Lee, Kendall H.

    2016-01-01

    Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301). PMID:27014033

  9. Response to Deep Brain Stimulation in Three Brain Targets with Implications in Mental Disorders: A PET Study in Rats

    PubMed Central

    Casquero-Veiga, Marta; Hadar, Ravit; Pascau, Javier; Winter, Christine; Desco, Manuel; Soto-Montenegro, María Luisa

    2016-01-01

    Objective To investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naïve rats. Methods 43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery. Stimulation period matched tracer uptake period. Images were acquired with a small-animal PET-CT scanner. Differences in glucose uptake between groups were assessed with Statistical Parametric Mapping. Results DBS induced site-specific metabolic changes, although a common increased metabolic activity in the piriform cortex was found for the three brain targets. mPFC-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG). NAcc-DBS increased metabolic activity in the subiculum and olfactory bulb, and decreased it in the BS, PAG, septum and hypothalamus. DM-DBS increased metabolic activity in the striatum, NAcc and thalamus and decreased it in the temporal and cingulate cortex. Conclusions DBS induced significant changes in 18FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of 18FDG uptake despite interacting with the same circuitries. This may have important implications to DBS research suggesting individualized target selection according to specific neural modulatory requirements. PMID:28033356

  10. Interdigitated array of Pt electrodes for electrical stimulation and engineering of aligned muscle tissue.

    PubMed

    Ahadian, Samad; Ramón-Azcón, Javier; Ostrovidov, Serge; Camci-Unal, Gulden; Hosseini, Vahid; Kaji, Hirokazu; Ino, Kosuke; Shiku, Hitoshi; Khademhosseini, Ali; Matsue, Tomokazu

    2012-09-21

    Engineered skeletal muscle tissues could be useful for applications in tissue engineering, drug screening, and bio-robotics. It is well-known that skeletal muscle cells are able to differentiate under electrical stimulation (ES), with an increase in myosin production, along with the formation of myofibers and contractile proteins. In this study, we describe the use of an interdigitated array of electrodes as a novel platform to electrically stimulate engineered muscle tissues. The resulting muscle myofibers were analyzed and quantified in terms of their myotube characteristics and gene expression. The engineered muscle tissues stimulated through the interdigitated array of electrodes demonstrated superior performance and maturation compared to the corresponding tissues stimulated through a conventional setup (i.e., through Pt wires in close proximity to the muscle tissue). In particular, the ES of muscle tissue (voltage 6 V, frequency 1 Hz and duration 10 ms for 1 day) through the interdigitated array of electrodes resulted in a higher degree of C2C12 myotube alignment (∼80%) as compared to ES using Pt wires (∼65%). In addition, higher amounts of C2C12 myotube coverage area, myotube length, muscle transcription factors and protein biomarkers were found for myotubes stimulated through the interdigitated array of electrodes compared to those stimulated using the Pt wires. Due to the wide array of potential applications of ES for two- and three-dimensional (2D and 3D) engineered tissues, the suggested platform could be employed for a variety of cell and tissue structures to more efficiently investigate their response to electrical fields.

  11. Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease.

    PubMed

    Bandini, Fabio; Primavera, Alberto; Pizzorno, Matteo; Cocito, Leonardo

    2007-08-01

    We describe two patients with Parkinson's disease (PD) who developed clinical criteria of pathological gambling addiction in the setting of increased dopamine replacement therapy (levodopa and dopamine agonist medications). The second patient showed also signs of dopamine dysregulation syndrome, with an addiction to dopaminergic medication. Neither patients responded to the standard therapy for gambling behavior, but dramatically improved after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) and early postoperative withdrawal of dopaminergic therapy. The possible therapeutic role of subthalamic nucleus deep brain stimulation (STN-DBS) on such a disabling behavior needs to be investigated prospectively.

  12. Flexible split-ring electrode for insect flight biasing using multisite neural stimulation.

    PubMed

    Tsang, Wei Mong; Stone, Alice L; Aldworth, Zane N; Hildebrand, John G; Daniel, Tom L; Akinwande, Akintunde Ibitayo; Voldman, Joel

    2010-07-01

    We describe a flexible multisite microelectrode for insect flight biasing using neural stimulation. The electrode is made of two layers of polyimide (PI) with gold sandwiched in between in a split-ring geometry. The split-ring design in conjunction with the flexibility of the PI allows for a simple insertion process and provides good attachment between the electrode and ventral nerve cord of the insect. Stimulation sites are located at the ends of protruding tips that are circularly distributed inside the split-ring structure. These protruding tips penetrate into the connective tissue surrounding the nerve cord. We have been able to insert the electrode into pupae of the giant sphinx moth Manduca sexta as early as seven days before the adult moth emerges, and we are able to use the multisite electrode to deliver electrical stimuli that evoke multidirectional, graded abdominal motions in both pupae and adult moths. Finally, in loosely tethered flight, we have used stimulation through the flexible microelectrodes to alter the abdominal angle, thus causing the flying moth to deviate to the left or right of its intended path.

  13. Enhanced control of electrochemical response in metallic materials in neural stimulation electrode applications

    SciTech Connect

    Watkins, K.G.; Steen, W.M.; Manna, I.

    1996-12-31

    New means have been investigated for the production of electrode devices (stimulation electrodes) which could be implanted in the human body in order to control pain, activate paralysed limbs or provide electrode arrays for cochlear implants for the deaf or for the relief of tinitus. To achieve this ion implantation and laser materials processing techniques were employed. Ir was ion implanted in Ti-6Al-4V alloy and the surface subsequently enriched in the noble metal by dissolution in sulphuric acid. For laser materials processing techniques, investigation has been carried out on the laser cladding and laser alloying of Ir in Ti wire. A particular aim has been the determination of conditions required for the formation of a two phase Ir, Ir-rich, and Ti-rich microstructure which would enable subsequent removal of the non-noble phase to leave a highly porous noble metal with large real surface area and hence improved charge carrying capacity compared with conventional non porous electrodes. Evaluation of the materials produced has been carried out using repetitive cyclic voltammetry, amongst other techniques. For laser alloyed Ir on Ti wire, it has been found that differences in the melting point and density of the materials makes control of the cladding or alloying process difficult. Investigation of laser process parameters for the control of alloying and cladding in this system was carried out and a set of conditions for the successful production of two phase Ir-rich and Ti-rich components in a coating layer with strong metallurgical bonding to the Ti alloy substrate was derived. The laser processed material displays excellent potential for further development in providing stimulation electrodes with the current carrying capacity of Ir but in a form which is malleable and hence capable of formation into smaller electrodes with improved spatial resolution compared with presently employed electrodes.

  14. Nanowire electrodes for high-density stimulation and measurement of neural circuits.

    PubMed

    Robinson, Jacob T; Jorgolli, Marsela; Park, Hongkun

    2013-01-01

    Brain-machine interfaces (BMIs) that can precisely monitor and control neural activity will likely require new hardware with improved resolution and specificity. New nanofabricated electrodes with feature sizes and densities comparable to neural circuits may lead to such improvements. In this perspective, we review the recent development of vertical nanowire (NW) electrodes that could provide highly parallel single-cell recording and stimulation for future BMIs. We compare the advantages of these devices and discuss some of the technical challenges that must be overcome for this technology to become a platform for next-generation closed-loop BMIs.

  15. Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI.

    PubMed

    Van Den Berge, Nathalie; Albaugh, Daniel L; Salzwedel, Andrew; Vanhove, Christian; Van Holen, Roel; Gao, Wei; Stuber, Garret D; Ian Shih, Yen-Yu

    2017-02-01

    The substantia nigra pars reticulata (SNr) and external globus pallidus (GPe) constitute the two major output targets of the rodent striatum. Both the SNr and GPe converge upon thalamic relay nuclei (directly or indirectly, respectively), and are traditionally modeled as functionally antagonistic relay inputs. However, recent anatomical and functional studies have identified unanticipated circuit connectivity in both the SNr and GPe, demonstrating their potential as far more than relay nuclei. In the present study, we employed simultaneous deep brain stimulation and functional magnetic resonance imaging (DBS-fMRI) with cerebral blood volume (CBV) measurements to functionally and unbiasedly map the circuit- and network level connectivity of the SNr and GPe. Sprague-Dawley rats were implanted with a custom-made MR-compatible stimulating electrode in the right SNr (n=6) or GPe (n=7). SNr- and GPe-DBS, conducted across a wide range of stimulation frequencies, revealed a number of surprising evoked responses, including unexpected CBV decreases within the striatum during DBS at either target, as well as GPe-DBS-evoked positive modulation of frontal cortex. Functional connectivity MRI revealed global modulation of neural networks during DBS at either target, sensitive to stimulation frequency and readily reversed following cessation of stimulation. This work thus contributes to a growing literature demonstrating extensive and unanticipated functional connectivity among basal ganglia nuclei.

  16. Visual cortex responses to suprachoroidal electrical stimulation of the retina: effects of electrode return configuration.

    PubMed

    Cicione, Rosemary; Shivdasani, Mohit N; Fallon, James B; Luu, Chi D; Allen, Penny J; Rathbone, Graeme D; Shepherd, Robert K; Williams, Chris E

    2012-06-01

    A clinically effective retinal prosthesis must evoke localized phosphenes in a retinotopic manner in response to stimulation of each of the retinal electrodes, evoke brightness cues over a wide dynamic range and function within safe stimulus limits. The effects of varying return configuration for retinal stimulation are currently unknown. To investigate this, we implanted a flexible, 7 × 12 electrode array into the suprachoroidal space of normally-sighted, anesthetized cats. Multi-unit activity in the primary visual cortex was recorded in response to electrical stimulation using various return configurations: monopolar vitreous (MPV), common ground (CG), hexagonal (HX), monopolar remote (MPR) and bipolar (BP_N). MPV stimulation was found to be the most charge efficient and was most likely to induce cortical activity within safe charge limits. HX and CG stimulation were found to exhibit greater retinal selectivity compared to the MPV return at the expense of lower cortical yield and higher P50 charge levels, while cortical selectivity was unaffected by choice of return. Responses using MPR and widely spaced BP_N configurations were similar to those using the MPV return. These results suggest that choice of return configuration for a retinal prosthesis will be balanced between resolution and stimulation within safe charge limits.

  17. Simulating pad-electrodes with high-definition arrays in transcranial electric stimulation

    NASA Astrophysics Data System (ADS)

    Kempe, René; Huang, Yu; Parra, Lucas C.

    2014-04-01

    Objective. Research studies on transcranial electric stimulation, including direct current, often use a computational model to provide guidance on the placing of sponge-electrode pads. However, the expertise and computational resources needed for finite element modeling (FEM) make modeling impractical in a clinical setting. Our objective is to make the exploration of different electrode configurations accessible to practitioners. We provide an efficient tool to estimate current distributions for arbitrary pad configurations while obviating the need for complex simulation software. Approach. To efficiently estimate current distributions for arbitrary pad configurations we propose to simulate pads with an array of high-definition (HD) electrodes and use an efficient linear superposition to then quickly evaluate different electrode configurations. Main results. Numerical results on ten different pad configurations on a normal individual show that electric field intensity simulated with the sampled array deviates from the solutions with pads by only 5% and the locations of peak magnitude fields have a 94% overlap when using a dense array of 336 electrodes. Significance. Computationally intensive FEM modeling of the HD array needs to be performed only once, perhaps on a set of standard heads that can be made available to multiple users. The present results confirm that by using these models one can now quickly and accurately explore and select pad-electrode montages to match a particular clinical need.

  18. Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Surface Area.

    PubMed

    Patel, Yogi A; Kim, Brian S; Rountree, William S; Butera, Robert J

    2017-03-17

    Kilohertz electrical stimulation (KES) induces repeatable and reversible conduction block of nerve activity and is a potential therapeutic option for various diseases and disorders resulting from pathological or undesired neurological activity. However successful translation of KES nerve block to clinical applications is stymied by many unknowns such as the relevance of the onset response, acceptable levels of waveform contamination, and optimal electrode characteristics. We investigated the role of electrode geometric surface area on the KES nerve block threshold using 20 and 40 kHz current-controlled sinusoidal KES. Electrodes were electrochemically characterized and used to characterize typical KES waveforms and electrode charge characteristics. KES nerve block amplitudes, onset duration, and recovery of normal conduction after delivery of KES were evaluated along with power requirements for effective KES nerve block. Results from this investigation demonstrate that increasing electrode geometric surface area provides for a more power efficient KES nerve block. Reductions in block threshold by increased electrode surface area were found to be KESfrequency dependent, with block thresholds and average power consumption reduced by >2x with 20 kHz KES waveforms and >3x for 40 kHz KES waveforms.

  19. Optical and electrochemical methods for determining the effective area and charge density of conducting polymer modified electrodes for neural stimulation.

    PubMed

    Harris, Alexander R; Molino, Paul J; Kapsa, Robert M I; Clark, Graeme M; Paolini, Antonio G; Wallace, Gordon G

    2015-01-06

    Neural stimulation is used in the cochlear implant, bionic eye, and deep brain stimulation, which involves implantation of an array of electrodes into a patient's brain. The current passed through the electrodes is used to provide sensory queues or reduce symptoms associated with movement disorders and increasingly for psychological and pain therapies. Poor control of electrode properties can lead to suboptimal performance; however, there are currently no standard methods to assess them, including the electrode area and charge density. Here we demonstrate optical and electrochemical methods for measuring these electrode properties and show the charge density is dependent on electrode geometry. This technique highlights that materials can have widely different charge densities but also large variation in performance. Measurement of charge density from an electroactive area may result in new materials and electrode geometries that improve patient outcomes and reduce side effects.

  20. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease

    PubMed Central

    Martel Sauvageau, Vincent; Roy, Johanna-Pascale; Cantin, Léo; Prud'Homme, Michel; Langlois, Mélanie; Macoir, Joël

    2015-01-01

    Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD. PMID:26558134

  1. Effectiveness of diaphragmatic stimulation with single-channel electrodes in rabbits*

    PubMed Central

    Ghedini, Rodrigo Guellner; Espinel, Julio de Oliveira; Felix, Elaine Aparecida; Paludo, Artur de Oliveira; Mariano, Rodrigo; Holand, Arthur Rodrigo Ronconi; Andrade, Cristiano Feijó

    2013-01-01

    Every year, a large number of individuals become dependent on mechanical ventilation because of a loss of diaphragm function. The most common causes are cervical spinal trauma and neuromuscular diseases. We have developed an experimental model to evaluate the performance of electrical stimulation of the diaphragm in rabbits using single-channel electrodes implanted directly into the muscle. Various current intensities (10, 16, 20, and 26 mA) produced tidal volumes above the baseline value, showing that this model is effective for the study of diaphragm performance at different levels of electrical stimulation PMID:24068272

  2. Entrainment of intestinal slow waves with electrical stimulation using intraluminal electrodes.

    PubMed

    Lin, X; Hayes, J; Peters, L J; Chen, J D

    2000-05-01

    The aim of this study was to investigate whether the intestinal stimulation would be feasible using a less invasive method: intraluminal electrodes. The study was performed in nine healthy hound dogs (15-26 kg). Four pairs of electrodes were implanted on the serosa of the jejunum at an interval of 5 cm with the most proximal pair 35 cm beyond the pylorus. An intestinal fistula was made 20 cm beyond the pylorus. Simultaneous recordings of intestinal myoelectrical activity were made for 2 h in the fasting state from both intraluminal and serosal electrodes. Various pacing parameters were tested. The frequency of the intestinal slow wave recorded from the intraluminal electrodes was identical to that from the serosal electrodes (18.78+/-0.3 cpm vs 18.75+/-0.3 cpm, r=0.99, p <0.001), and so was the percentage of normal 17-22 cycles/ min waves (95.83+/-3.9% vs 98.16+/-1.33%, r=0.96, p<0.01). A complete entrainment of the intestinal slow wave was achieved in every dog with electrical stimulation using intraluminal ring electrodes. The effective pacing parameters were pulse width of 70 ms, amplitude of 4 mA and frequency of 1.1 IF (intrinsic frequency). The time required for the entrainment of the intestinal slow wave with intraluminal pacing was 25.0+/-2.1 s. The maximum driven frequency was found to be 1.43+/-0.01 IF. The results reveal that intraluminal pacing is an effective and efficient method for the entrainment of intestinal slow waves. It may become a potential approach for the treatment of intestinal motor disorders associated with myoelectrical abnormalities.

  3. A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning.

    PubMed

    Wang, Ching-Fu; Yang, Shih-Hung; Lin, Sheng-Huang; Chen, Po-Chuan; Lo, Yu-Chun; Pan, Han-Chi; Lai, Hsin-Yi; Liao, Lun-De; Lin, Hui-Ching; Chen, Hsu-Yan; Huang, Wei-Chen; Huang, Wun-Jhu; Chen, You-Yin

    2017-02-24

    Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption. However, when the association between the biomarkers of the model and stimulation is unclear, it is difficult to develop an optimal control scheme for other DBS applications, i.e., DBS-enhanced instrumental learning. Furthermore, few studies have investigated the effect of closed-loop DBS control for cognition function, such as instrumental skill learning, and have been implemented in simulation environments. In this paper, we proposed a proof-of-principle design for a closed-loop DBS system, cognitive-enhancing DBS (ceDBS), which enhanced skill learning based on in vivo experimental data. The ceDBS acquired local field potential (LFP) signal from the thalamic central lateral (CL) nuclei of animals through a neural signal processing system. A strong coupling of the theta oscillation (4-7 Hz) and the learning period was found in the water reward-related lever-pressing learning task. Therefore, the theta-band power ratio, which was the averaged theta band to averaged total band (1-55 Hz) power ratio, could be used as a physiological marker for enhancement of instrumental skill learning. The on-line extraction of the theta-band power ratio was implemented on a field-programmable gate array (FPGA). An autoregressive with exogenous inputs (ARX)-based predictor was designed to construct a CL-thalamic DBS model and forecast the future physiological marker according to the past physiological marker and applied DBS. The prediction could further assist the design of

  4. [Finite element analysis of electric field of extracellular stimulation of optic nerve with a spiral cuff electrode].

    PubMed

    Guo, Hongwei; Qiao, Qingli; Luo, Fang

    2012-10-01

    In order to study the underlying electrode-nerve functional mechanism, optimize the electrode design and guide the prosthesis application, we applied finite element method to analyze the spatial distribution of electric field generated by optic nerve electrical stimulation with spiral cuff electrode. A macroscopic cylindrical model of optic nerve was elaborated, taking into account of electrode contact configurations and possible variations of the thickness of cerebrospinal fluid (CSF). By building an appropriate mesh on this model and under some boundary conditions, the finite element method was applied to compute the 3D electric field generated by the electrode with finite element software COMSOL Multiphysics. The stimulation results indicated that, under the same conditions of stimulation, the longitudinal tripolar electrode structure could generate larger current density than that of biopolar electrode structure (located in the opposite of nerve trunk). However biopolar electrode structure requirs less leads, and is more easily implanted. By means of parametric sweep, the results suggest that, with the increase of the CSF thickness and a higher conductivity of CSF than those of other tissues, the distribution of electric field generated by electrodes is extended but scattered, and the diffuse current distribution makes nerve stimulation less effective.

  5. Vertical electric field stimulated neural cell functionality on porous amorphous carbon electrodes.

    PubMed

    Jain, Shilpee; Sharma, Ashutosh; Basu, Bikramjit

    2013-12-01

    We demonstrate the efficacy of amorphous macroporous carbon substrates as electrodes to support neuronal cell proliferation and differentiation in electric field mediated culture conditions. The electric field was applied perpendicular to carbon substrate electrode, while growing mouse neuroblastoma (N2a) cells in vitro. The placement of the second electrode outside of the cell culture medium allows the investigation of cell response to electric field without the concurrent complexities of submerged electrodes such as potentially toxic electrode reactions, electro-kinetic flows and charge transfer (electrical current) in the cell medium. The macroporous carbon electrodes are uniquely characterized by a higher specific charge storage capacity (0.2 mC/cm(2)) and low impedance (3.3 kΩ at 1 kHz). The optimal window of electric field stimulation for better cell viability and neurite outgrowth is established. When a uniform or a gradient electric field was applied perpendicular to the amorphous carbon substrate, it was found that the N2a cell viability and neurite length were higher at low electric field strengths (≤ 2.5 V/cm) compared to that measured without an applied field (0 V/cm). While the cell viability was assessed by two complementary biochemical assays (MTT and LDH), the differentiation was studied by indirect immunostaining. Overall, the results of the present study unambiguously establish the uniform/gradient vertical electric field based culture protocol to either enhance or to restrict neurite outgrowth respectively at lower or higher field strengths, when neuroblastoma cells are cultured on porous glassy carbon electrodes having a desired combination of electrochemical properties.

  6. Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease

    PubMed Central

    Zrinzo, L.; Martinez-Torres, I.; Frost, E.; Pinto, S.; Foltynie, T.; Holl, E.; Petersen, E.; Roughton, M.; Hariz, M.I.; Limousin, P.

    2011-01-01

    Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change. Methods: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. Results: Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2% ± 20.15% off-medication and 16.9% ± 21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6% ± 5.5% and 4.5% ± 8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. Conclusion: The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1

  7. Trimodal nanoelectrode array for precise deep brain stimulation: prospects of a new technology based on carbon nanofiber arrays.

    PubMed

    Li, J; Andrews, R J

    2007-01-01

    Although deep brain stimulation (DBS) has recently been shown to be effective for neurological disorders such as Parkinson's disease, there are many limitations of the current technology: the large size of current microelectrodes (approximately 1 mm diameter); the lack of monitoring of local brain electrical activity and neurotransmitters (e.g. dopamine in Parkinson's disease); the open-loop nature of the stimulation (i.e. not guided by brain electrochemical activity). Reducing the size of the monitoring and stimulating electrodes by orders of magnitude (to the size of neural elements) allows remarkable improvements in both monitoring (spatial resolution, temporal resolution, and sensitivity) and stimulation. Carbon nanofiber nanoelectrode technology offers the possibility of trimodal arrays (monitoring electrical activity, monitoring neurotransmitter levels, precise stimulation). DBS can then be guided by changes in brain electrical activity and/or neurotransmitter levels (i.e. closed-loop DBS). Here, we describe the basic manufacture and electrical characteristics of a prototype nanoelectrode array for DBS, as well as preliminary studies with electroconductive polymers necessary to optimize DBS in vivo. An approach such as the nanoelectrode array described here may offer a generic electrical-neural interface for use in various neural prostheses.

  8. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... complaints. The MVDDS licensee must satisfy all complaints of interference to DBS customers of record which... ensure that the EPFD from its transmitting antenna at all DBS customers of record locations is below the... obtain a signed written agreement from DBS customers of record stating that they are aware of and...

  9. Electrodic voltages accompanying stimulated bioremediation of a uranium-contaminated aquifer

    SciTech Connect

    Williams, K.H.; N'Guessan, A.L.; Druhan, J.; Long, P.E.; Hubbard, S.S.; Lovley, D.R.; Banfield, J.F.

    2009-11-15

    The inability to track the products of subsurface microbial activity during stimulated bioremediation has limited its implementation. We used spatiotemporal changes in electrodic potentials (EP) to track the onset and persistence of stimulated sulfate-reducing bacteria in a uranium-contaminated aquifer undergoing acetate amendment. Following acetate injection, anomalous voltages approaching -900 mV were measured between copper electrodes within the aquifer sediments and a single reference electrode at the ground surface. Onset of EP anomalies correlated in time with both the accumulation of dissolved sulfide and the removal of uranium from groundwater. The anomalies persisted for 45 days after halting acetate injection. Current-voltage and current-power relationships between measurement and reference electrodes exhibited a galvanic response, with a maximum power density of 10 mW/m{sup 2} during sulfate reduction. We infer that the EP anomalies resulted from electrochemical differences between geochemically reduced regions and areas having higher oxidation potential. Following the period of sulfate reduction, EP values ranged from -500 to -600 mV and were associated with elevated concentrations of ferrous iron. Within 10 days of the voltage decrease, uranium concentrations rebounded from 0.2 to 0.8 {mu}M, a level still below the background value of 1.5 {mu}M. These findings demonstrate that EP measurements provide an inexpensive and minimally invasive means for monitoring the products of stimulated microbial activity within aquifer sediments and are capable of verifying maintenance of redox conditions favorable for the stability of bioreduced contaminants, such as uranium.

  10. Non-penetrating round window electrode stimulation for tinnitus therapy followed by cochlear implantation.

    PubMed

    Wenzel, Gentiana I; Sarnes, Petra; Warnecke, Athanasia; Stöver, Timo; Jäger, Burkard; Lesinski-Schiedat, Anke; Lenarz, Thomas

    2015-11-01

    One main theory behind the origin of tinnitus is based on the idea that alterations of the spontaneous electrical activity within the auditory system lead to abnormal firing patterns in the affected nervous structures [1]. A possible therapeutic option is the use of electrical stimulation of the auditory nerve for the recovery or at least limitation of the abnormal firing pattern to a level that can be easily tolerated by the patient. The Tinnelec Implant consists of a single non-penetrating stimulation electrode connected to a Neurelec cochlear implant system. As a first feasibility study, before starting implantations in hearing patients, we thought to assess the potential of the Tinnelec stimulation to treat tinnitus in unilateral deaf patients, analysing hereby its effectivity and risks. Three patients suffering from unilateral tinnitus resistant to pharmacological treatment and ipsilateral severe to profound sensorineural hearing loss/deafness were implanted with a Tinnelec system between September 2007 and July 2008, at the ENT Department of Hannover Medical School. The stimulation strategy was chosen to induce alleviation of the tinnitus through suppression, masking and/or habituation and the response of each patient on the treatment was monitored using a visual analogue scale (VAS) on loudness and annoyance of tinnitus, mood of the patient, as well as the tinnitus handicap inventory (THI). All patients had a benefit from the electrical stimulation for their tinnitus (THI-score improvement of 20-70), however, not all participants profited from the Tinnelec system in same way and degree. In one patient, despite good results, the device had to be replaced with a conventional cochlear implant because of Tinnelec-independent increase in hearing loss on the contralateral ear. Additionally, due to the extension of cochlear implant indications, the devices of the other two patients have been meanwhile replaced with a conventional cochlear implant to benefit

  11. Quantitative analysis of axonal fiber activation evoked by deep brain stimulation via activation density heat maps

    PubMed Central

    Hartmann, Christian J.; Chaturvedi, Ashutosh; Lujan, J. Luis

    2015-01-01

    Background: Cortical modulation is likely to be involved in the various therapeutic effects of deep brain stimulation (DBS). However, it is currently difficult to predict the changes of cortical modulation during clinical adjustment of DBS. Therefore, we present a novel quantitative approach to estimate anatomical regions of DBS-evoked cortical modulation. Methods: Four different models of the subthalamic nucleus (STN) DBS were created to represent variable electrode placements (model I: dorsal border of the posterolateral STN; model II: central posterolateral STN; model III: central anteromedial STN; model IV: dorsal border of the anteromedial STN). Axonal fibers of passage near each electrode location were reconstructed using probabilistic tractography and modeled using multi-compartment cable models. Stimulation-evoked activation of local axon fibers and corresponding cortical projections were modeled and quantified. Results: Stimulation at the border of the STN (models I and IV) led to a higher degree of fiber activation and associated cortical modulation than stimulation deeply inside the STN (models II and III). A posterolateral target (models I and II) was highly connected to cortical areas representing motor function. Additionally, model I was also associated with strong activation of fibers projecting to the cerebellum. Finally, models III and IV showed a dorsoventral difference of preferentially targeted prefrontal areas (models III: middle frontal gyrus; model IV: inferior frontal gyrus). Discussion: The method described herein allows characterization of cortical modulation across different electrode placements and stimulation parameters. Furthermore, knowledge of anatomical distribution of stimulation-evoked activation targeting cortical regions may help predict efficacy and potential side effects, and therefore can be used to improve the therapeutic effectiveness of individual adjustments in DBS patients. PMID:25713510

  12. What is the optimal anodal electrode position for inducing corticomotor excitability changes in transcranial direct current stimulation?

    PubMed

    Lee, Minji; Kim, Yun-Hee; Im, Chang-Hwan; Kim, Jung-Hoon; Park, Chang-hyun; Chang, Won Hyuk; Lee, Ahee

    2015-01-01

    Transcranial direct current stimulation (tDCS) non-invasively modulates brain function by inducing neuronal excitability. The conventional hot spot for inducing the highest current density in the hand motor area may not be the optimal site for effective stimulation. In this study, we investigated the influence of the center position of the anodal electrode on changes in motor cortical excitability. We considered three tDCS conditions in 16 healthy subjects: (i) real stimulation with the anodal electrode located at the conventional hand motor hot spot determined by motor evoked potentials (MEPs); (ii) real stimulation with the anodal electrode located at the point with the highest current density in the hand motor area as determined by electric current simulation; and (iii) sham stimulation. Motor cortical excitability as measured by MEP amplitude increased after both real stimulation conditions, but not after sham stimulation. Stimulation using the simulation-derived anodal electrode position, which was found to be posterior to the MEP hot spot for all subjects, induced higher motor cortical excitability. Individual positioning of the anodal electrode, based on the consideration of anatomical differences between subjects, appears to be important for maximizing the effects of tDCS.

  13. Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings

    PubMed Central

    Langevin, Jean-Philippe; Chen, James W. Y.; Koek, Ralph J.; Sultzer, David L.; Mandelkern, Mark A.; Schwartz, Holly N.; Krahl, Scott E.

    2016-01-01

    The amygdala plays a critical role in emotion regulation. It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. We aim to describe our targeting technique, and intra-operative and post-operative electrodiagnostic findings associated with the placement of deep brain stimulation (DBS) electrodes in the amygdala. We used a transfrontal approach to implant DBS electrodes in the basolateral nucleus of the amygdala (BLn) of a patient suffering from severe post-traumatic stress disorder. We used microelectrode recording (MER) and awake intra-operative neurostimulation to assist with the placement. Post-operatively, the patient underwent monthly surveillance electroencephalograms (EEG). MER predicted the trajectory of the electrode through the amygdala. The right BLn showed a higher spike frequency than the left BLn. Intra-operative neurostimulation of the BLn elicited pleasant memories. The monthly EEG showed the presence of more sleep patterns over time with DBS. BLn DBS electrodes can be placed using a transfrontal approach. MER can predict the trajectory of the electrode in the amygdala and it may reflect the BLn neuronal activity underlying post-traumatic stress disorder PTSD. The EEG findings may underscore the reduction in anxiety. PMID:27517963

  14. Effective parameters for stimulation of dissociated cultures using multi-electrode arrays.

    PubMed

    Wagenaar, Daniel A; Pine, Jerome; Potter, Steve M

    2004-09-30

    Electrical stimulation through multi-electrode arrays is used to evoke activity in dissociated cultures of cortical neurons. We study the efficacies of a variety of pulse shapes under voltage control as well as current control, and determine useful parameter ranges that optimize efficacy while preventing damage through electrochemistry. For any pulse shape, stimulation is found to be mediated by negative currents. We find that positive-then-negative biphasic voltage-controlled pulses are more effective than any of the other pulse shapes tested, when compared at the same peak voltage. These results suggest that voltage-control, with its inherent control over limiting electrochemistry, may be advantageous in a wide variety of stimulation scenarios, possibly extending to in-vivo experiments.

  15. Theoretical analysis of the local field potential in deep brain stimulation applications.

    PubMed

    Lempka, Scott F; McIntyre, Cameron C

    2013-01-01

    Deep brain stimulation (DBS) is a common therapy for treating movement disorders, such as Parkinson's disease (PD), and provides a unique opportunity to study the neural activity of various subcortical structures in human patients. Local field potential (LFP) recordings are often performed with either intraoperative microelectrodes or DBS leads and reflect oscillatory activity within nuclei of the basal ganglia. These LFP recordings have numerous clinical implications and might someday be used to optimize DBS outcomes in closed-loop systems. However, the origin of the recorded LFP is poorly understood. Therefore, the goal of this study was to theoretically analyze LFP recordings within the context of clinical DBS applications. This goal was achieved with a detailed recording model of beta oscillations (∼20 Hz) in the subthalamic nucleus. The recording model consisted of finite element models of intraoperative microelectrodes and DBS macroelectrodes implanted in the brain along with multi-compartment cable models of STN projection neurons. Model analysis permitted systematic investigation into a number of variables that can affect the composition of the recorded LFP (e.g. electrode size, electrode impedance, recording configuration, and filtering effects of the brain, electrode-electrolyte interface, and recording electronics). The results of the study suggest that the spatial reach of the LFP can extend several millimeters. Model analysis also showed that variables such as electrode geometry and recording configuration can have a significant effect on LFP amplitude and spatial reach, while the effects of other variables, such as electrode impedance, are often negligible. The results of this study provide insight into the origin of the LFP and identify variables that need to be considered when analyzing LFP recordings in clinical DBS applications.

  16. Theoretical Analysis of the Local Field Potential in Deep Brain Stimulation Applications

    PubMed Central

    Lempka, Scott F.; McIntyre, Cameron C.

    2013-01-01

    Deep brain stimulation (DBS) is a common therapy for treating movement disorders, such as Parkinson’s disease (PD), and provides a unique opportunity to study the neural activity of various subcortical structures in human patients. Local field potential (LFP) recordings are often performed with either intraoperative microelectrodes or DBS leads and reflect oscillatory activity within nuclei of the basal ganglia. These LFP recordings have numerous clinical implications and might someday be used to optimize DBS outcomes in closed-loop systems. However, the origin of the recorded LFP is poorly understood. Therefore, the goal of this study was to theoretically analyze LFP recordings within the context of clinical DBS applications. This goal was achieved with a detailed recording model of beta oscillations (∼20 Hz) in the subthalamic nucleus. The recording model consisted of finite element models of intraoperative microelectrodes and DBS macroelectrodes implanted in the brain along with multi-compartment cable models of STN projection neurons. Model analysis permitted systematic investigation into a number of variables that can affect the composition of the recorded LFP (e.g. electrode size, electrode impedance, recording configuration, and filtering effects of the brain, electrode-electrolyte interface, and recording electronics). The results of the study suggest that the spatial reach of the LFP can extend several millimeters. Model analysis also showed that variables such as electrode geometry and recording configuration can have a significant effect on LFP amplitude and spatial reach, while the effects of other variables, such as electrode impedance, are often negligible. The results of this study provide insight into the origin of the LFP and identify variables that need to be considered when analyzing LFP recordings in clinical DBS applications. PMID:23555799

  17. Effects of antidromic and orthodromic activation of STN afferent axons during DBS in Parkinson's disease: a simulation study.

    PubMed

    Kang, Guiyeom; Lowery, Madeleine M

    2014-01-01

    Recent studies suggest that subthalamic nucleus (STN)-Deep Brain Stimulation (DBS) may exert at least part of its therapeutic effect through the antidromic suppression of pathological oscillations in the cortex in 6-OHDA treated rats and in parkinsonian patients. STN-DBS may also activate STN neurons by initiating action potential propagation in the orthodromic direction, similarly resulting in suppression of pathological oscillations in the STN. While experimental studies have provided strong evidence in support of antidromic stimulation of cortical neurons, it is difficult to separate relative contributions of antidromic and orthodromic effects of STN-DBS. The aim of this computational study was to examine the effects of antidromic and orthodromic activation on neural firing patterns and beta-band (13-30 Hz) oscillations in the STN and cortex during DBS of STN afferent axons projecting from the cortex. High frequency antidromic stimulation alone effectively suppressed simulated beta activity in both the cortex and STN-globus pallidus externa (GPe) network. High frequency orthodromic stimulation similarly suppressed beta activity within the STN and GPe through the direct stimulation of STN neurons driven by DBS at the same frequency as the stimulus. The combined effect of both antidromic and orthodromic stimulation modulated cortical activity antidromically while simultaneously orthodromically driving STN neurons. While high frequency DBS reduced STN beta-band power, low frequency stimulation resulted in resonant effects, increasing beta-band activity, consistent with previous experimental observations. The simulation results indicate effective suppression of simulated oscillatory activity through both antidromic stimulation of cortical neurons and direct orthodromic stimulation of STN neurons. The results of the study agree with experimental recordings of STN and cortical neurons in rats and support the therapeutic potential of stimulation of cortical neurons.

  18. Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans.

    PubMed

    Sims-Williams, Hugh; Matthews, Julian C; Talbot, Peter S; Love-Jones, Sarah; Brooks, Jonathan Cw; Patel, Nikunj K; Pickering, Anthony E

    2017-02-01

    Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [(11)C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [(11)C]DPN and [(15)O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [(11)C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [(11)C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit.

  19. Multichannel DBS halftoning for improved texture quality

    NASA Astrophysics Data System (ADS)

    Slavuj, Radovan; Pedersen, Marius

    2015-01-01

    The paper aims to develop a method for multichannel halftoning based on the Direct Binary Search (DBS) algorithm. We integrate specifics and benefits of multichannel printing into the halftoning method in order to further improve texture quality of DBS and to create halftoning that would suit for multichannel printing. Originally, multichannel printing is developed for an extended color gamut, at the same time additional channels can help to improve individual and combined texture of color halftoning. It does so in a similar manner to the introduction of the light colors (diluted inks) in printing. Namely, if one observes Red, Green and Blue inks as the light version of the M+Y, C+Y, C+M combinations, the visibility of the unwanted halftoning textures can be reduced. Analogy can be extent to any number of ink combinations, or Neugebauer Primaries (NPs) as the alternative building blocks. The extended variability of printing spatially distributed NPs could provide many practical solution and improvements in color accuracy, image quality, and could enable spectral printing. This could be done by selection of NPs per dot area location based on the constraint of the desired reproduction. Replacement with brighter NP at the location could induce a color difference where a tradeoff between image quality and color accuracy is created. With multichannel enabled DBS haftoning, we are able to reduce visibility of the textures, to provide better rendering of transitions, especially in mid and dark tones.

  20. The RAI DBS experiment with Olympus

    NASA Astrophysics Data System (ADS)

    Castelli, Enzo

    The Italian broadcasting network (RAI) has studied the development of a national DBS service in an effort to outline a proposal for a space segment configuration compatible with development of new services, including HDTV. Proposals so far considered feature the integration of RAI's channel on Olympus in a future operational system and after extensive experimental use. Contents of the experimental program are discussed, and need for a broadcasting standard which considers projected introduction of HDTV is noted. The debate between RAI and consumer electronic industries on the use of broadcasting standards is outlined. The position of RAI in the context of HDTV and DBS is defined and the issue of determining the most effective transmission standard during the experimental stage is raised. It is pointed out that, in the absence of new production facilities for HDTV, the maximum quality which MAC will yield will be that of PAL since programs must be produced in PAL and then converted into MAC. Two alternatives for strategy on the use of broadcasting standards for DBS are offered. Finally, technical experiments and a market survey are discussed.

  1. Deep brain stimulation for chronic pain.

    PubMed

    Boccard, Sandra G J; Pereira, Erlick A C; Aziz, Tipu Z

    2015-10-01

    Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.

  2. Quantifying the Neural Elements Activated and Inhibited by Globus Pallidus Deep Brain Stimulation

    PubMed Central

    Johnson, Matthew D.; McIntyre, Cameron C.

    2008-01-01

    Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective therapy option for controlling the motor symptoms of medication-refractory Parkinson's disease and dystonia. Despite the clinical successes of GPi DBS, the precise therapeutic mechanisms are unclear and questions remain on the optimal electrode placement and stimulation parameter selection strategies. In this study, we developed a three-dimensional computational model of GPi-DBS in nonhuman primates to investigate how membrane channel dynamics, synaptic inputs, and axonal collateralization contribute to the neural responses generated during stimulation. We focused our analysis on three general neural elements that surround GPi-DBS electrodes: GPi somatodendritic segments, GPi efferent axons, and globus pallidus pars externa (GPe) fibers of passage. During high-frequency electrical stimulation (136 Hz), somatic activity in the GPi showed interpulse excitatory phases at 1–3 and 4–5.5 ms. When including stimulation-induced GABAA and AMPA receptor dynamics into the model, the somatic firing patterns continued to be entrained to the stimulation, but the overall firing rate was reduced (78.7 to 25.0 Hz, P < 0.001). In contrast, axonal output from GPi neurons remained largely time-locked to each pulse of the stimulation train. Similar entrainment was also observed in GPe efferents, a majority of which have been shown to project through GPi en route to the subthalamic nucleus. The models suggest that pallidal DBS may have broader network effects than previously realized and the modes of therapy may depend on the relative proportion of GPi and/or GPe efferents that are directly affected by the stimulation. PMID:18768645

  3. Pedunculopontine nucleus evoked potentials from subthalamic nucleus stimulation in Parkinson's disease.

    PubMed

    Neagu, Bogdan; Tsang, Eric; Mazzella, Filomena; Hamani, Clement; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Chen, Robert

    2013-12-01

    The effects of subthalamic nucleus (STN) stimulation on the pedunculopontine nucleus area (PPNR) evoked activities were examined in two patients with Parkinson's disease. The patients had previously undergone bilateral STN deep brain stimulation (DBS) and subsequently received unilateral DBS electrodes in the PPNR. Evoked potentials were recorded from the local field potentials (LFP) from the PPNR with STN stimulation at different frequencies and bipolar contacts. Ipsilateral and contralateral short latency (<2ms) PPNR responses were evoked from left but not from right STN stimulation. In both patients, STN stimulation evoked contralateral PPNR responses at medium latencies between 41 and 45ms. Cortical evoked potentials to single pulse STN stimulation were observed at latencies between 18 and 27ms. These results demonstrate a functional connection between the STN and the PPNR. It likely involves direct projections between the STN and PPNR or polysynaptic pathways with thalamic or cortical relays.

  4. Deep Brain Stimulation Frequency—A Divining Rod for New and Novel Concepts of Nervous System Function and Therapy

    PubMed Central

    Montgomery, Erwin B.; He, Huang

    2016-01-01

    The efficacy of Deep Brain Stimulation (DBS) for an expanding array of neurological and psychiatric disorders demonstrates directly that DBS affects the basic electroneurophysiological mechanisms of the brain. The increasing array of active electrode configurations, stimulation currents, pulse widths, frequencies, and pulse patterns provides valuable tools to probe electroneurophysiological mechanisms. The extension of basic electroneurophysiological and anatomical concepts using sophisticated computational modeling and simulation has provided relatively straightforward explanations of all the DBS parameters except frequency. This article summarizes current thought about frequency and relevant observations. Current methodological and conceptual errors are critically examined in the hope that future work will not replicate these errors. One possible alternative theory is presented to provide a contrast to many current theories. DBS, conceptually, is a noisy discrete oscillator interacting with the basal ganglia–thalamic–cortical system of multiple re-entrant, discrete oscillators. Implications for positive and negative resonance, stochastic resonance and coherence, noisy synchronization, and holographic memory (related to movement generation) are presented. The time course of DBS neuronal responses demonstrates evolution of the DBS response consistent with the dynamics of re-entrant mechanisms. Finally, computational modeling demonstrates identical dynamics as seen by neuronal activities recorded from human and nonhuman primates, illustrating the differences of discrete from continuous harmonic oscillators and the power of conceptualizing the nervous system as composed on interacting discrete nonlinear oscillators. PMID:27548234

  5. How electrode montage affects transcranial direct current stimulation of the human motor cortex.

    PubMed

    Salvador, Ricardo; Wenger, Cornelia; Nitsche, Michael A; Miranda, Pedro C

    2015-01-01

    Several different electrode configurations were originally proposed to induce excitability changes in the hand area of the motor cortex in transcranial direct current stimulation (tDCS). However only one was found to efficiently affect cortical excitability: anode/cathode over the primary motor cortex and return electrode placed over the contralateral orbit (M-CF configuration). In this work we used the finite element method to calculate the electric field (E-field) induced in a realistic human head model in all the proposed electrode configurations. In order to analyze the results, average values of the E-field's magnitude and polar/azimuthal angles were calculated in several cortical motor and premotor areas which may have an effect on the output of the primary motor cortex. The average E-field's magnitude at the hand-knob (HK) was similar between the M-CF configuration (0.16 V/m) and a few other tested configurations, the same happening for the average polar angle (129°). However this configuration achieved the highest mean E-field values over premotor (PM) areas (0.21 V/m). These results show that the polar angle and the average magnitude of the E-field evaluated at the HK and at the PM cortex might be important parameters in predicting the success of a specific electrode montage in tDCS.

  6. Enhanced tissue integration of implantable electrodes for sensing, and stimulation, via radio frequency glow discharge

    NASA Astrophysics Data System (ADS)

    O'Connor, Laurie M.

    Biopotential electrodes are conductive materials that convert electronic currents to or from ionic currents for sensing, and stimulating specific tissue sites for medical applications. Implanted electrodes become "walled off" by the foreign body tissue reactions producing poorly attached scar capsules dominated by surrounding dense collagenous lamellae and source fibroblasts which are electrically resistive. The conductive interstitial fluid that is typical between an electrode and the resistive capsule allows spurious current paths. The insulating layer increases the distance between the electrode and the target sites and poor attachment often results in electrode migration within the host tissue. This investigation tested the hypothesis that surface-energy modulation of electrodes, via Radio Frequency Glow Discharge Treatment (RFGDT), can improve the performance of tissue-implantable electrodes by reducing the foreign body tissue reaction and enhancing interfacial bonding between the tissue and electrode material. Previously published findings were reproduced in a pilot study of explanted reference grade medical-grade methyl silicone (PDMS) and commercially pure titanium (cpTi) materials and their tissue capsules from 30-day subcutaneous exposures in Balb/C mice. The low-critical surface tension PDMS produced thick, dense, poorly attached scar capsules while the higher-surface-energy commercially pure titanium (cpTi) produced more cellular and strongly attached tissue layers difficult to delaminate from the biomaterial. For the main body of work, cpTi, capacitor-grade Tantalum (Ta), and synthetic heart valve-quality Pyrolytic Carbon (PyC) were evaluated, representative of potential high-surface-energy implant electrode materials. Their surface characteristics were determined as-manufactured and after Radio Frequency Glow Discharge Treatment (RFGDT) by Critical Surface Tension (CST) measurement, Scanning Electron Microscopy (SEM), Energy Dispersive X

  7. Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles

    NASA Astrophysics Data System (ADS)

    Badia, Jordi; Boretius, Tim; Andreu, David; Azevedo-Coste, Christine; Stieglitz, Thomas; Navarro, Xavier

    2011-06-01

    The selection of a suitable nerve electrode for neuroprosthetic applications implies a trade-off between invasiveness and selectivity, wherein the ultimate goal is achieving the highest selectivity for a high number of nerve fascicles by the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME) is intended to be transversally inserted into the peripheral nerve and to be useful to selectively activate subsets of axons in different fascicles within the same nerve. We present a comparative study of TIME, LIFE and multipolar cuff electrodes for the selective stimulation of small nerves. The electrodes were implanted on the rat sciatic nerve, and the activation of gastrocnemius, plantar and tibialis anterior muscles was recorded by EMG signals. Thus, the study allowed us to ascertain the selectivity of stimulation at the interfascicular and also at the intrafascicular level. The results of this study indicate that (1) intrafascicular electrodes (LIFE and TIME) provide excitation circumscribed to the implanted fascicle, whereas extraneural electrodes (cuffs) predominantly excite nerve fascicles located superficially; (2) the minimum threshold for muscle activation with TIME and LIFE was significantly lower than with cuff electrodes; (3) TIME allowed us to selectively activate the three tested muscles when stimulating through different active sites of one device, both at inter- and intrafascicular levels, whereas selective activation using multipolar cuff (with a longitudinal tripolar stimulation configuration) was only possible for two muscles, at the interfascicular level, and LIFE did not activate selectively more than one muscle in the implanted nerve fascicle.

  8. Evaluation of poly(3,4-ethylenedioxythiophene)/carbon nanotube neural electrode coatings for stimulation in the dorsal root ganglion

    PubMed Central

    Kolarcik, Christi L.; Catt, Kasey; Rost, Erika; Albrecht, Ingrid N.; Bourbeau, Dennis; Du, Zhanhong; Kozai, Takashi D.Y.; Luo, Xiliang; Weber, Douglas J.; Cui, X. Tracy

    2015-01-01

    Objective The dorsal root ganglion (DRG) is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity. Approach Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multiwall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as the result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB. Main Results Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced. Significance This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities. PMID:25485675

  9. Evaluation of poly(3,4-ethylenedioxythiophene)/carbon nanotube neural electrode coatings for stimulation in the dorsal root ganglion

    NASA Astrophysics Data System (ADS)

    Kolarcik, Christi L.; Catt, Kasey; Rost, Erika; Albrecht, Ingrid N.; Bourbeau, Dennis; Du, Zhanhong; Kozai, Takashi D. Y.; Luo, Xiliang; Weber, Douglas J.; Cui, X. Tracy

    2015-02-01

    Objective. The dorsal root ganglion is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity. Approach. Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-wall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as a result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB. Main results. Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced. Significance. This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities.

  10. Effects of Intramuscular Electrical Stimulation Using Inversely Placed Electrodes on Myofascial Pain Syndrome in the Shoulder: A Case Series

    PubMed Central

    Mathias, Lawrence; Thakur, Ajay; Kumar, Dhanesh

    2016-01-01

    Myofascial pain syndrome (MPS) is one of the common musculoskeletal conditions of the shoulder which may develop sensory-motor and autonomic dysfunctions at the various level of the neuromuscular system. The pain and dysfunction caused by MPS were primarily treated with physical therapy and pharmacological agents in order to achieve painfree movements. However, in recent years intramuscular electrical stimulation (IMES) with conventional electrode placement was used by researchers to maximise therapeutic values. But, in this study an inverse electrode placement was used to deliver electrical impulses intramuscularly to achieve neuro-modulation at the various level of the nervous system. Nine patients with MPS were treated with intramuscular electrode stimulation using inversely placed electrodes for a period of three weeks. All nine subjects recovered from their shoulder pain and disability within the few weeks of intervention. So, this inverse electrode placement may be more appropriate for chronic pain management. PMID:27103970

  11. Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation.

    PubMed

    Li, S; Arbuthnott, G W; Jutras, M J; Goldberg, J A; Jaeger, D

    2007-12-01

    Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

  12. Active books: the design of an implantable stimulator that minimizes cable count using integrated circuits very close to electrodes.

    PubMed

    Liu, Xiao; Demosthenous, Andreas; Vanhoestenberghe, Anne; Jiang, Dai; Donaldson, Nick

    2012-06-01

    This paper presents an integrated stimulator that can be embedded in implantable electrode books for interfacing with nerve roots at the cauda equina. The Active Book overcomes the limitation of conventional nerve root stimulators which can only support a small number of stimulating electrodes due to cable count restriction through the dura. Instead, a distributed stimulation system with many tripole electrodes can be configured using several Active Books which are addressed sequentially. The stimulator was fabricated in a 0.6-μm high-voltage CMOS process and occupies a silicon area of 4.2 × 6.5 mm(2). The circuit was designed to deliver up to 8 mA stimulus current to tripole electrodes from an 18 V power supply. Input pad count is limited to five (two power and three control lines) hence requiring a specific procedure for downloading stimulation commands to the chip and extracting information from it. Supported commands include adjusting the amplitude of stimulus current, varying the current ratio at the two anodes in each channel, and measuring relative humidity inside the chip package. In addition to stimulation mode, the chip supports quiescent mode, dissipating less than 100 nA current from the power supply. The performance of the stimulator chip was verified with bench tests including measurements using tripoles in saline.

  13. Charge trapping induced by plasma in alumina electrode surface investigated by thermoluminescence and optically stimulated luminescence

    SciTech Connect

    Ambrico, P. F.; Ambrico, M.; Schiavulli, L.; Ligonzo, T.; Augelli, V.

    2009-02-02

    The plasma of a dielectric barrier discharge can fill traps in the alumina that cover the electrode. Trap energies and lifetimes are estimated by thermoluminescence and optically stimulated luminescence. Comparison with similar results for traps created by other radiation sources clarifies the mechanisms regulating this effect. Alumina's trap energies are approximately 1 eV, and the traps remain active for several days after plasma exposure. These results could be important to keep dielectric barrier discharge plasmas uniform since a trapped charge can be an electron reservoir.

  14. Artifact properties of carbon nanotube yarn electrode in magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Jiang, C. Q.; Hao, H. W.; Li, L. M.

    2013-04-01

    Objective. Deep brain stimulating (DBS) is a rapidly developing therapy that can treat many refractory neurological diseases. However, the traditional DBS electrodes which are made of Pt-Ir alloy may induce severe field distortions in magnetic resonance imaging (MRI) which leads to artifacts that will lower the local image quality and cause inconvenience or interference. A novel DBS electrode made from carbon nanotube yarns (CNTYs) is brought up to reduce the artifacts. This study is therefore to evaluate the artifact properties of the novel electrode. Approach. We compared its MR artifact characteristics with the Pt-Ir electrode in water phantom, including its artifact behaviors at different orientations as well as at various off-center positions, using both spin echo (SE) and gradient echo (GE) sequences, and confirmed its performance in vivo. Main results. The results in phantom showed that the CNTY electrode artifacts reduced as much as 62% and 74% on GE and SE images, respectively, compared to the Pt-Ir one. And consistent behaviors were confirmed in vivo. The susceptibility difference was identified as the dominant cause in producing artifacts. Significance. Employing the CNTY electrode may generate much less field distortion in the vicinity, improve local MR image quality and possibly be beneficial in various aspects.

  15. Evaluation of Interactive Visualization on Mobile Computing Platforms for Selection of Deep Brain Stimulation Parameters.

    PubMed

    Butson, Christopher R; Tamm, Georg; Jain, Sanket; Fogal, Thomas; Krüger, Jens

    2013-01-01

    In recent years, there has been significant growth in the use of patient-specific models to predict the effects of neuromodulation therapies such as deep brain stimulation (DBS). However, translating these models from a research environment to the everyday clinical workflow has been a challenge, primarily due to the complexity of the models and the expertise required in specialized visualization software. In this paper, we deploy the interactive visualization system ImageVis3D Mobile, which has been designed for mobile computing devices such as the iPhone or iPad, in an evaluation environment to visualize models of Parkinson's disease patients who received DBS therapy. Selection of DBS settings is a significant clinical challenge that requires repeated revisions to achieve optimal therapeutic response, and is often performed without any visual representation of the stimulation system in the patient. We used ImageVis3D Mobile to provide models to movement disorders clinicians and asked them to use the software to determine: 1) which of the four DBS electrode contacts they would select for therapy; and 2) what stimulation settings they would choose. We compared the stimulation protocol chosen from the software versus the stimulation protocol that was chosen via clinical practice (independent of the study). Lastly, we compared the amount of time required to reach these settings using the software versus the time required through standard practice. We found that the stimulation settings chosen using ImageVis3D Mobile were similar to those used in standard of care, but were selected in drastically less time. We show how our visualization system, available directly at the point of care on a device familiar to the clinician, can be used to guide clinical decision making for selection of DBS settings. In our view, the positive impact of the system could also translate to areas other than DBS.

  16. Optimization of focality and direction in dense electrode array transcranial direct current stimulation (tDCS)

    PubMed Central

    Guler, Seyhmus; Dannhauer, Moritz; Erem, Burak; Macleod, Rob; Tucker, Don; Turovets, Sergei; Luu, Phan; Erdogmus, Deniz; Brooks, Dana H.

    2016-01-01

    Objective Transcranial direct current stimulation (tDCS) aims to alter brain function noninvasively via electrodes placed on the scalp. Conventional tDCS uses two relatively large patch electrodes to deliver electrical currents to the brain region of interest (ROI). Recent studies have shown that using dense arrays containing up to 512 smaller electrodes may increase the precision of targeting ROIs. However, this creates a need for methods to determine effective and safe stimulus patterns as the degrees of freedom is much higher with such arrays. Several approaches to this problem have appeared in the literature. In this paper, we describe a new method for calculating optimal electrode stimulus pattern for targeted and directional modulation in dense array tDCS which differs in some important aspects with methods reported to date. Approach We optimize stimulus pattern of dense arrays with fixed electrode placement to maximize the current density in a particular direction in the ROI. We impose a flexible set of safety constraints on the current power in the brain, individual electrode currents, and total injected current, to protect subject safety. The proposed optimization problem is convex and thus efficiently solved using existing optimization software to find unique and globally optimal electrode stimulus patterns. Main results Solutions for four anatomical ROIs based on a realistic head model are shown as exemplary results. To illustrate the differences between our approach and previously introduced methods, we compare our method with two of the other leading methods in the literature. We also report on extensive simulations that show the effect of the values chosen for each proposed safety constraint bound on the optimized stimulus patterns. Significance The proposed optimization approach employs volume based ROIs, easily adapts to different sets of safety constraints, and takes negligible time to compute. In-depth comparison study gives insight into the

  17. Optimization of focality and direction in dense electrode array transcranial direct current stimulation (tDCS)

    NASA Astrophysics Data System (ADS)

    Guler, Seyhmus; Dannhauer, Moritz; Erem, Burak; Macleod, Rob; Tucker, Don; Turovets, Sergei; Luu, Phan; Erdogmus, Deniz; Brooks, Dana H.

    2016-06-01

    Objective. Transcranial direct current stimulation (tDCS) aims to alter brain function non-invasively via electrodes placed on the scalp. Conventional tDCS uses two relatively large patch electrodes to deliver electrical current to the brain region of interest (ROI). Recent studies have shown that using dense arrays containing up to 512 smaller electrodes may increase the precision of targeting ROIs. However, this creates a need for methods to determine effective and safe stimulus patterns as the number of degrees of freedom is much higher with such arrays. Several approaches to this problem have appeared in the literature. In this paper, we describe a new method for calculating optimal electrode stimulus patterns for targeted and directional modulation in dense array tDCS which differs in some important aspects with methods reported to date. Approach. We optimize stimulus pattern of dense arrays with fixed electrode placement to maximize the current density in a particular direction in the ROI. We impose a flexible set of safety constraints on the current power in the brain, individual electrode currents, and total injected current, to protect subject safety. The proposed optimization problem is convex and thus efficiently solved using existing optimization software to find unique and globally optimal electrode stimulus patterns. Main results. Solutions for four anatomical ROIs based on a realistic head model are shown as exemplary results. To illustrate the differences between our approach and previously introduced methods, we compare our method with two of the other leading methods in the literature. We also report on extensive simulations that show the effect of the values chosen for each proposed safety constraint bound on the optimized stimulus patterns. Significance. The proposed optimization approach employs volume based ROIs, easily adapts to different sets of safety constraints, and takes negligible time to compute. An in-depth comparison study gives

  18. Nerve cuff electrode using embedded magnets and its application to hypoglossal nerve stimulation

    NASA Astrophysics Data System (ADS)

    Seo, Jungmin; Hye Wee, Jee; Hoan Park, Jeong; Park, Pona; Kim, Jeong-Whun; Kim, Sung June

    2016-12-01

    Objective. A novel nerve cuff electrode with embedded magnets was fabricated and developed. In this study, a pair of magnets was fully embedded and encapsulated in a liquid crystal polymer (LCP) substrate to utilize magnetic force in order to replace the conventional installing techniques of cuff electrodes. In vitro and in vivo experiments were conducted to evaluate the feasibility of the magnet-embedded nerve cuff electrode (MENCE). Lastly, several issues pertaining to the MENCE such as the cuff-to-nerve diameter ratio, the force of the magnets, and possible concerns were discussed in the discussion section. Approach. Electrochemical impedance spectrum and cyclic voltammetry assessments were conducted to measure the impedance and charge storage capacity of the cathodal phase (CSCc). The MENCE was installed onto the hypoglossal nerve (HN) of a rabbit and the movement of the genioglossus was recorded through C-arm fluoroscopy while the HN was stimulated by a pulsed current. Main results. The measured impedance was 0.638 ∠ -67.8° kΩ at 1 kHz and 5.27 ∠ -82.1° kΩ at 100 Hz. The average values of access resistance and cut-off frequency were 0.145 kΩ and 3.98 kHz, respectively. The CSCc of the electrode was measured as 1.69 mC cm-2 at the scan rate of 1 mV s-1. The movement of the genioglossus contraction was observed under a pulsed current with an amplitude level of 0.106 mA, a rate of 0.635 kHz, and a duration of 0.375 ms applied through the MENCE. Significance. A few methods to close and secure cuff electrodes have been researched, but they are associated with several drawbacks. To overcome these, we used magnetic force as a closing method of the cuff electrode. The MENCE can be precisely installed on a target nerve without any surgical techniques such as suturing or molding. Furthermore, it is convenient to remove the installed MENCE because it requires little force to detach one magnet from the other, enabling repeatable installation and removal. We

  19. Transcutaneous neuromuscular electrical stimulation: influence of electrode positioning and stimulus amplitude settings on muscle response.

    PubMed

    Gobbo, M; Gaffurini, P; Bissolotti, L; Esposito, F; Orizio, C

    2011-10-01

    The aim of the study was to investigate the influence of two different transcutaneous neuromuscular electrical stimulation procedures on evoked muscle torque and local tissue oxygenation. In the first one (MP mode), the cathode was facing the muscle main motor point and stimulus amplitude was set to the level eliciting the maximal myoelectrical activation according to the amplitude of the evoked electromyogram (EMG); in the second one (RC mode), the electrodes were positioned following common reference charts for electrode placement while stimulus amplitude was set according to subject tolerance. Tibialis Anterior (TA) and Vastus Lateralis (VL) muscles of 10 subjects (28.4 ± 8.2 years) were tested in specific dynamometers to measure the evoked isometric torque. The EMG and near-infrared spectroscopy probes were placed on muscle belly to detect the electrical activity and local metabolic modifications of the stimulated muscle, respectively. The stimulation protocol consisted of a gradually increasing frequency ramp from 2 to 50 Hz in 7.5 s. Compared to RC mode, in MP mode the contractile parameters (peak twitch, tetanic torque, area under the torque build-up) and the metabolic solicitation (oxygen consumption and hyperemia due to metabolites accumulation) resulted significantly higher for both TA and VL muscles. MP mode resulted also to be more comfortable for the subjects. Based on the assumption that proper mechanical and metabolic stimuli are necessary to induce muscle strengthening, our results witness the importance of an optimized, i.e., comfortable and effective, stimulation to promote the aforementioned muscle adaptive modifications.

  20. Computational Study on Subdural Cortical Stimulation - The Influence of the Head Geometry, Anisotropic Conductivity, and Electrode Configuration

    PubMed Central

    Kim, Donghyeon; Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

    2014-01-01

    Subdural cortical stimulation (SuCS) is a method used to inject electrical current through electrodes beneath the dura mater, and is known to be useful in treating brain disorders. However, precisely how SuCS must be applied to yield the most effective results has rarely been investigated. For this purpose, we developed a three-dimensional computational model that represents an anatomically realistic brain model including an upper chest. With this computational model, we investigated the influence of stimulation amplitudes, electrode configurations (single or paddle-array), and white matter conductivities (isotropy or anisotropy). Further, the effects of stimulation were compared with two other computational models, including an anatomically realistic brain-only model and the simplified extruded slab model representing the precentral gyrus area. The results of voltage stimulation suggested that there was a synergistic effect with the paddle-array due to the use of multiple electrodes; however, a single electrode was more efficient with current stimulation. The conventional model (simplified extruded slab) far overestimated the effects of stimulation with both voltage and current by comparison to our proposed realistic upper body model. However, the realistic upper body and full brain-only models demonstrated similar stimulation effects. In our investigation of the influence of anisotropic conductivity, model with a fixed ratio (1∶10) anisotropic conductivity yielded deeper penetration depths and larger extents of stimulation than others. However, isotropic and anisotropic models with fixed ratios (1∶2, 1∶5) yielded similar stimulation effects. Lastly, whether the reference electrode was located on the right or left chest had no substantial effects on stimulation. PMID:25229673

  1. Deep Brain Stimulation

    PubMed Central

    Chen, X.L.; Xiong, Y.Y.; Xu, G.L.; Liu, X.F.

    2013-01-01

    Deep brain stimulation (DBS) has provided remarkable therapeutic benefits for people with a variety of neurological disorders. Despite the uncertainty of the precise mechanisms underlying its efficacy, DBS is clinically effective in improving motor function of essential tremor, Parkinson's disease and primary dystonia and in relieving obsessive-compulsive disorder. Recently, this surgical technique has continued to expand to other numerous neurological diseases with encouraging results. This review highlighted the current and potential future clinical applications of DBS. PMID:25187779

  2. Motor cortex stimulation in Parkinson's disease.

    PubMed

    De Rose, Marisa; Guzzi, Giusy; Bosco, Domenico; Romano, Mary; Lavano, Serena Marianna; Plastino, Massimiliano; Volpentesta, Giorgio; Marotta, Rosa; Lavano, Angelo

    2012-01-01

    Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment was performed by total UPDRS, UPDRS III total, UPDRS III-items 27-31, UPDRS IV, and UPDRS II before implantation in off-medication and on-medication states and after surgery at 1, 3, 6, 12, 18, 24, and 36 months in on-medication/on-stimulation and off-medication/on-stimulation states. We assessed changes of quality of life, throughout the Parkinson's disease quality of life scale (PDQoL-39), and the dose of anti-Parkinson's disease medications, throughout the Ldopa equivalent daily dose (LEDD). During off-medication state, we observed moderate and transitory reduction of total UPDRS and UPDRS total scores and significant and long-lasting improvement in UPDRS III items 27-31 score for axial symptoms. There was marked reduction of UPDRS IV score and LEDD. PDQL-39 improvement was also significant. No important complications and adverse events occurred.

  3. Motor Cortex Stimulation in Parkinson's Disease

    PubMed Central

    De Rose, Marisa; Guzzi, Giusy; Bosco, Domenico; Romano, Mary; Lavano, Serena Marianna; Plastino, Massimiliano; Volpentesta, Giorgio; Marotta, Rosa; Lavano, Angelo

    2012-01-01

    Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment was performed by total UPDRS, UPDRS III total, UPDRS III-items 27–31, UPDRS IV, and UPDRS II before implantation in off-medication and on-medication states and after surgery at 1, 3, 6, 12, 18, 24, and 36 months in on-medication/on-stimulation and off-medication/on-stimulation states. We assessed changes of quality of life, throughout the Parkinson's disease quality of life scale (PDQoL-39), and the dose of anti-Parkinson's disease medications, throughout the Ldopa equivalent daily dose (LEDD). During off-medication state, we observed moderate and transitory reduction of total UPDRS and UPDRS total scores and significant and long-lasting improvement in UPDRS III items 27–31 score for axial symptoms. There was marked reduction of UPDRS IV score and LEDD. PDQL-39 improvement was also significant. No important complications and adverse events occurred. PMID:23213520

  4. Evaluation of Platinum-Black Stimulus Electrode Array for Electrical Stimulation of Retinal Cells in Retinal Prosthesis System

    NASA Astrophysics Data System (ADS)

    Watanabe, Taiichiro; Kobayashi, Risato; Komiya, Ken; Fukushima, Takafumi; Tomita, Hiroshi; Sugano, Eriko; Kurino, Hiroyuki; Tanaka, Tetsu; Tamai, Makoto; Koyanagi, Mitsumasa

    2007-04-01

    A retinal prosthesis system with a three-dimensionally (3D) stacked LSI chip has been proposed. We fabricated a new implantable stimulus electrode array deposited with Platinum-black (Pt-b) on a polyimide-based flexible printed circuit (FPC) for the electrical stimulation of the retinal cells. Impedance measurement of the Pt-b electrode-electrolyte interface in a saline solution was performed and the Pt-b electrode realized a very low impedance. The power consumption at the electrode array when retinal cells were stimulated by a stimulus current was evaluated. The power consumption of the Pt-b stimulus electrode array was 91% lower than that of a previously fabricated Al stimulus electrode array due to a convexo-concave surface. In the cytotoxicity test (CT), we confirmed that Pt implantation induced no cellular degeneration of the rat retina. In the animal experiments, electrically evoked potential (EEP) was successfully recorded using Japanese white rabbits. These results indicate that electrical stimulation using the Pt-b stimulus electrode array can restore visual sensation.

  5. Influence of implantation on the electrochemical properties of smooth and porous TiN coatings for stimulation electrodes

    NASA Astrophysics Data System (ADS)

    Meijs, S.; Sørensen, C.; Sørensen, S.; Rechendorff, K.; Fjorback, M.; Rijkhoff, N. J. M.

    2016-04-01

    Objective. To determine whether changes in electrochemical properties of porous titanium nitride (TiN) electrodes as a function of time after implantation are different from those of smooth TiN electrodes. Approach. Eight smooth and 8 porous TiN coated electrodes were implanted in 8 rats. Before implantation, voltage transients, cyclic voltammograms and impedance spectra were recorded in phosphate buffered saline (PBS). After implantation, these measurements were done weekly to investigate how smooth and porous electrodes were affected by implantation. Main results. The electrode capacitance of the porous TiN electrodes decreased more than the capacitance of the smooth electrodes due to acute implantation under fast measurement conditions (such as stimulation pulses). This indicates that protein adhesion presents a greater diffusion limitation for counter-ions for the porous than for the smooth electrodes. The changes in electrochemical properties during the implanted period were similar for smooth and porous TiN electrodes, indicating that cell adhesion poses a similar diffusion limitation for smooth and porous electrodes. Significance. This knowledge can be used to optimize the porous structure of the TiN film, so that the effect of protein adhesion on the electrochemical properties is diminished. Alternatively, an additional coating could be applied on the porous TiN that would prevent or minimize protein adhesion.

  6. Deep brain stimulation mechanisms: the control of network activity via neurochemistry modulation.

    PubMed

    McIntyre, Cameron C; Anderson, Ross W

    2016-10-01

    Deep brain stimulation (DBS) has revolutionized the clinical care of late-stage Parkinson's disease and shows promise for improving the treatment of intractable neuropsychiatric disorders. However, after over 25 years of clinical experience, numerous questions still remain on the neurophysiological basis for the therapeutic mechanisms of action. At their fundamental core, the general purpose of electrical stimulation therapies in the nervous system are to use the applied electric field to manipulate the opening and closing of voltage-gated sodium channels on neurons, generate stimulation induced action potentials, and subsequently, control the release of neurotransmitters in targeted pathways. Historically, DBS mechanisms research has focused on characterizing the effects of stimulation on neurons and the resulting impact on neuronal network activity. However, when electrodes are placed within the central nervous system, glia are also being directly (and indirectly) influenced by the stimulation. Mounting evidence shows that non-neuronal tissue can play an important role in modulating the neurochemistry changes induced by DBS. The goal of this review is to evaluate how DBS effects on both neuronal and non-neuronal tissue can potentially work together to suppress oscillatory activity (and/or information transfer) between brain regions. These resulting effects of ~ 100 Hz electrical stimulation help explain how DBS can disrupt pathological network activity in the brain and generate therapeutic effects in patients. Deep brain stimulation is an effective clinical technology, but detailed therapeutic mechanisms remain undefined. This review provides an overview of the leading hypotheses, which focus on stimulation-induced disruption of network oscillations and integrates possible roles for non-neuronal tissue in explaining the clinical response to therapeutic stimulation. This article is part of a special issue on Parkinson disease.

  7. Metal nanoparticles in DBS card materials modification

    NASA Astrophysics Data System (ADS)

    Metelkin, A.; Frolov, G.; Kuznetsov, D.; Kolesnikov, E.; Chuprunov, K.; Kondakov, S.; Osipov, A.; Samsonova, J.

    2015-11-01

    In the recent years the method of collecting and storing Dried Blood Spots (DBS) on special cellulose membrane (paper) has gained wide popularity. But possible damage of biosamples caused by microorganisms in case of their incomplete drying is a disadvantage of the method. It can be overcome by treating sample-collection membranes with colloidal solutions of metal nanoparticles, having antibacterial effect. The team studied antibacterial properties of nonwoven material samples with various coatings (alcohol sols of copper, aluminium, iron, titanium, silver and vanadium nanoparticles). Colloidal solutions of nanoparticles were obtained by means of electroerosion method with further low-temperature plasma condensation. Antibacterial activity of fiberglass and cellulose membrane samples with nanoparticle coatings was studied using B. cereus and plaque bacteria cultures. It was revealed that nanostructured coatings can suppress bacterial activity; in addition they can diffuse from the membrane surface into medium which leads to widening the areas of inhibiting testing cultures’ growth. Thus, membrane materials treatment with alcohol-sols of metal nanoparticles can be seen as promising for conferring antibacterial properties to DBS carriers.

  8. Thin-film micro-electrode stimulation of the cochlea in rats exposed to aminoglycoside induced hearing loss.

    PubMed

    Allitt, B J; Harris, A R; Morgan, S J; Clark, G M; Paolini, A G

    2016-01-01

    The multi-channel cochlear implant (CI) provides sound and speech perception to thousands of individuals who would otherwise be deaf. Broad activation of auditory nerve fibres when using a CI results in poor frequency discrimination. The CI also provides users with poor amplitude perception due to elicitation of a narrow dynamic range. Provision of more discrete frequency perception and a greater control over amplitude may allow users to better distinguish speech in noise and to segregate sound sources. In this research, thin-film (TF) high density micro-electrode arrays and conventional platinum ring electrode arrays were used to stimulate the cochlea of rats administered sensorineural hearing loss (SNHL) via ototoxic insult, with neural responses taken at 434 multiunit clusters in the central nucleus of the inferior colliculus (CIC). Threshold, dynamic range and broadness of response were used to compare electrode arrays. A stronger current was required to elicit CIC threshold when using the TF array compared to the platinum ring electrode array. TF stimulation also elicited a narrower dynamic range than the PR counterpart. However, monopolar stimulation using the TF array produced more localised CIC responses than other stimulation strategies. These results suggest that individuals with SNHL could benefit from micro stimulation of the cochlea using a monopolar configuration which may provide discrete frequency perception when using TF electrode arrays.

  9. Inter-electrode tissue resistance is not affected by tissue oedema when electrically stimulating the lower limb of sepsis patients.

    PubMed

    Durfee, William K; Young, Joseph R; Ginz, Hans F

    2014-05-01

    ICU patients typically are given large amounts of fluid and often develop oedema. The purpose of this study was to evaluate whether the oedema would change inter-electrode resistance and, thus, require a different approach to using non-invasive electrical stimulation of nerves to assess muscle force. Inter-electrode tissue resistance in the lower leg was measured by applying a 300 µs constant current pulse and measuring the current through and voltage across the stimulating electrodes. The protocol was administered to nine ICU patients with oedema, eight surgical patients without oedema and eight healthy controls. No significant difference in inter-electrode resistance was found between the three groups. For all groups, resistance decreased as stimulation current increased. In conclusion, inter-electrode resistance in ICU patients with severe oedema is the same as the resistance in regular surgical patients and healthy controls. This means that non-invasive nerve stimulation devices do not need to be designed to accommodate different resistances when used with oedema patients; however, surface stimulation does require higher current levels with oedema patients because of the increased distance between the skin surface and the targeted nerve or muscle.

  10. Cerebellar tDCS Effects on Conditioned Eyeblinks using Different Electrode Placements and Stimulation Protocols.

    PubMed

    Beyer, Linda; Batsikadze, Giorgi; Timmann, Dagmar; Gerwig, Marcus

    2017-01-01

    There is good evidence that the human cerebellum is involved in the acquisition and timing of classically conditioned eyeblink responses (CRs). Animal studies suggest that the cerebellum is also important in CR extinction and savings. Cerebellar transcranial direct current stimulation (tDCS) was reported to modulate CR acquisition and timing in a polarity dependent manner. To extent previous findings three experiments were conducted using standard delay eyeblink conditioning. In a between-group design, effects of tDCS were assessed with stimulation over the right cerebellar hemisphere ipsilaterally to the unconditioned stimulus (US). An extracephalic reference electrode was used in Experiment 1 and a cephalic reference in Experiment 2. In both parts the influence on unconditioned eyeblink responses (UR) was investigated by starting stimulation in the second half of the pseudoconditioning phase lasting throughout the first half of paired trials. In a third experiment, effects of cerebellar tDCS during 40 extinction trials were assessed on extinction and reacquisition on the next day. In each experiment, 30 subjects received anodal, cathodal or sham stimulation in a double-blinded fashion. Using the extracephalic reference electrode, no significant effects on CR incidences comparing stimulation groups were observed. Using the cephalic reference anodal as well as cathodal cerebellar tDCS increased CR acquisition compared to sham only on a trend level. Analysis of timing parameters did not reveal significant effects on CR onset and peaktime latencies nor on UR timing. In the third experiment, cerebellar tDCS during extinction trials had no significant effect on extinction and savings on the next day. The present study did not reveal clear polarity dependent effects of cerebellar tDCS on CR acquisition and timing as previously described. Weaker effects may be explained by start of tDCS before the learning phase i.e., offline, individual thresholds and current flow based

  11. Cerebellar tDCS Effects on Conditioned Eyeblinks using Different Electrode Placements and Stimulation Protocols

    PubMed Central

    Beyer, Linda; Batsikadze, Giorgi; Timmann, Dagmar; Gerwig, Marcus

    2017-01-01

    There is good evidence that the human cerebellum is involved in the acquisition and timing of classically conditioned eyeblink responses (CRs). Animal studies suggest that the cerebellum is also important in CR extinction and savings. Cerebellar transcranial direct current stimulation (tDCS) was reported to modulate CR acquisition and timing in a polarity dependent manner. To extent previous findings three experiments were conducted using standard delay eyeblink conditioning. In a between-group design, effects of tDCS were assessed with stimulation over the right cerebellar hemisphere ipsilaterally to the unconditioned stimulus (US). An extracephalic reference electrode was used in Experiment 1 and a cephalic reference in Experiment 2. In both parts the influence on unconditioned eyeblink responses (UR) was investigated by starting stimulation in the second half of the pseudoconditioning phase lasting throughout the first half of paired trials. In a third experiment, effects of cerebellar tDCS during 40 extinction trials were assessed on extinction and reacquisition on the next day. In each experiment, 30 subjects received anodal, cathodal or sham stimulation in a double-blinded fashion. Using the extracephalic reference electrode, no significant effects on CR incidences comparing stimulation groups were observed. Using the cephalic reference anodal as well as cathodal cerebellar tDCS increased CR acquisition compared to sham only on a trend level. Analysis of timing parameters did not reveal significant effects on CR onset and peaktime latencies nor on UR timing. In the third experiment, cerebellar tDCS during extinction trials had no significant effect on extinction and savings on the next day. The present study did not reveal clear polarity dependent effects of cerebellar tDCS on CR acquisition and timing as previously described. Weaker effects may be explained by start of tDCS before the learning phase i.e., offline, individual thresholds and current flow based

  12. High-resolution extracellular stimulation of dispersed hippocampal culture with high-density CMOS multielectrode array based on non-Faradaic electrodes.

    PubMed

    Lei, N; Ramakrishnan, S; Shi, P; Orcutt, J S; Yuste, R; Kam, L C; Shepard, K L

    2011-08-01

    We introduce a method to electrically stimulate individual neurons at single-cell resolution in arbitrary spatiotemporal patterns with precise control over stimulation thresholds. By exploiting a custom microelectronic chip, up to 65,000 non-Faradaic electrodes can be uniquely addressed with electrode density exceeding 6500 electrodes mm(-2). We demonstrate extracellular stimulation of dispersed primary hippocampal neuronal cultures using the chip at single-cell resolution.

  13. Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease

    PubMed Central

    Hickey, Patrick; Stacy, Mark

    2016-01-01

    Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management. PMID:27199637

  14. Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease.

    PubMed

    Hickey, Patrick; Stacy, Mark

    2016-01-01

    Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management.

  15. Analyzing the tradeoff between electrical complexity and accuracy in patient-specific computational models of deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Howell, Bryan; McIntyre, Cameron C.

    2016-06-01

    Objective. Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. Approach. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Main results. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. Significance. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.

  16. On the single sweep processing of auditory brainstem responses: click vs. chirp stimulations and active vs. passive electrodes.

    PubMed

    Corona-Strauss, Farah I; Delb, Wolfgang; Bloching, Marc; Strauss, Daniel J

    2008-01-01

    We have recently shown that click evoked auditory brainstem responses (ABRs) single sweeps can efficiently be processed by a hybrid novelty detection system. This approach allowed for the objective detection of hearing thresholds in a fraction of time of conventional schemes, making it appropriate for the efficient implementation of newborn hearing screening procedures. It is the objective of this study to evaluate whether this approach might further be improved by different stimulation paradigms and electrode settings. In particular, we evaluate chirp stimulations which compensate the basilar-membrane dispersion and active electrodes which are less sensitive to movements. This is the first study which is directed to a single sweep processing of chirp evoked ABRs. By concentrating on transparent features and a minimum number of adjustable parameters, we present an objective comparison of click vs.chirp stimulations and active vs. passive electrodes in the ultrafast ABR detection. We show that chirp evoked brainstem responses and active electrodes might improve the single sweeps analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs for the objective determination of hearing thresholds can further be improved by the use of optimized chirp stimulations and active electrodes.

  17. An implantable device for neuropsychiatric rehabilitation by chronic deep brain stimulation in freely moving rats

    PubMed Central

    Wang, Chenguang; Zhang, Fuqiang; Jia, Hong

    2017-01-01

    Successful practice of clinical deep brain stimulation (DBS) calls for basic research on the mechanisms and explorations of new indications in animals. In the article, a new implantable, single-channel, low-power miniature device is proposed, which may transmit pulses chronically into the brain nucleus of freely moving rats. The DBS system consists of an implantable pulse generator (IPG), a bipolar electrode, and an external programmer. The IPG circuit module is assembled as a 20-mm diameter circular board and fixed on a rat’s skull together with an electrode and battery. The rigid electrode may make its fabrication and implantation more easy. The external programmer is designed for bidirectional communication with the IPG by a telecontrol transceiver and adjusts stimulation parameters. A biological validation was performed in which the effects of electrical stimulation in brain nucleus accumbens were detected. The programmed parameters were accurate, implant steady, and power sufficient to allow stimulation for more than 3 months. The larger area of the electrode tip provided a moderate current or charge density and minimized the damage from electrochemistry and pyroelectricity. The rats implanted with the device showed a reduction in morphine-induced conditioned place preference after high-frequency stimulation. In conclusion, the DBS device is based on the criteria of simple technology, minimal invasion, low cost, small in size, light-weight, and wireless controlled. This shows that our DBS device is appropriate and can be used for preclinical studies, indicating its potential utility in the therapy and rehabilitation of neuropsychiatric disorders. PMID:28121810

  18. Anesthetic Challenges for Deep Brain Stimulation: A Systematic Approach

    PubMed Central

    Chakrabarti, Rajkalyan; Ghazanwy, Mahmood; Tewari, Anurag

    2014-01-01

    Ablative intracranial surgery for Parkinson's disease has advanced to embedding electrodes into precise areas of the basal ganglia. Electrode implantation surgery, referred to as deep brain stimulation (DBS), is preferred in view of its reversibility, adjustability, and capability to be safely performed bilaterally. DBS is been increasingly used for other movement disorders, intractable tremors epilepsy, and sometimes chronic pain. Anesthesiologists need to amalgamate the knowledge of neuroanatomical structures and surgical techniques involved in placement of microelectrodes in defined cerebral target areas. Perioperative verbal communication with the patient during the procedure is quintessential and may attenuate the need for pharmacological agents. This review will endeavor to assimilate the present knowledge regarding the patient selection, available/practiced anesthesia regimens, and perioperative complications after our thorough search for literature published between 1991 and 2013. PMID:25210668

  19. Biofouling resistance of boron-doped diamond neural stimulation electrodes is superior to titanium nitride electrodes in vivo

    NASA Astrophysics Data System (ADS)

    Meijs, S.; Alcaide, M.; Sørensen, C.; McDonald, M.; Sørensen, S.; Rechendorff, K.; Gerhardt, A.; Nesladek, M.; Rijkhoff, N. J. M.; Pennisi, C. P.

    2016-10-01

    Objective. The goal of this study was to assess the electrochemical properties of boron-doped diamond (BDD) electrodes in relation to conventional titanium nitride (TiN) electrodes through in vitro and in vivo measurements. Approach. Electrochemical impedance spectroscopy, cyclic voltammetry and voltage transient (VT) measurements were performed in vitro after immersion in a 5% albumin solution and in vivo after subcutaneous implantation in rats for 6 weeks. Main results. In contrast to the TiN electrodes, the capacitance of the BDD electrodes was not significantly reduced in albumin solution. Furthermore, BDD electrodes displayed a decrease in the VTs and an increase in the pulsing capacitances immediately upon implantation, which remained stable throughout the whole implantation period, whereas the opposite was the case for the TiN electrodes. Significance. These results reveal that BDD electrodes possess a superior biofouling resistance, which provides significantly stable electrochemical properties both in protein solution as well as in vivo compared to TiN electrodes.

  20. Electrochemomechanical deformation (ECMD) of PPyDBS in free standing film formation and trilayer designs

    NASA Astrophysics Data System (ADS)

    Aydemir, Nihan; Tamm, Tarmo; Travas-Sejdic, Jadranka; Kilmartin, Paul A.; Aabloo, Alvo; Kiefer, Rudolf

    2014-03-01

    An investigation is reported into the electrochemomechanical deformation (ECMD) of polypyrrole (PPy) doped with dodecylbenzenesulfonate (DBS) in the form of freestanding films and deposited onto conductive substrates (chemically fixed poly-3,4-(ethylenedioxythiophene, PEDOT) based on PVdF (poly(vinylidenefluoride)). Linear actuation has been achieved starting from a trilayer bending actuator design with a stretchable middle layer. To allow evaluation of the proposed design, commercially available PVdF membranes were chosen as model material. For bending trilayer functionality, electronic separation of both electrode layers is essential, but in order to obtain linear actuation, the CP layers on either side are connected to form a single working electrode. The PPyDBS free standing films and PPyDBS deposited on PEDOT-PVdF-PEDOT were investigated by electrochemical methods (cyclic voltammetry, square wave potentials) in a 4-methyl-1,3-dioxolan-2-one (propylene carbonate, PC) solution of tetrabutylammonium trifluoromethanesulfonate (TBACF3SO3). This study also presents a novel method of utilizing scanning ion-conductance microscopy (SICM) to accurately examine the electrochemical redox behavior of the surface layer of the linear actuator using a micropipette tip.

  1. International regulation of DBS transmission and uplinks

    NASA Astrophysics Data System (ADS)

    de Leo, M.; Ciavoli Cortelli, L. A.

    The history of ITU regulation of TV and radio transmission via satellite is reviewed, with an emphasis on the provisions for Europe, and technological implications are discussed. Consideration is given to the frequency bands for DBS, planning for the 12-GHz band, planning for Regions 1 and 3, WARC-BS-1977 provisions for Regions 1 and 3, RARC-SAT-R2 (1983) provisions for Region 2, and uplink regulations. It is pointed out that improvements in receiver technology (permitting lower satellite EIRP, improved reception quality and availability, and/or smaller antennas) can be exploited within the WARC-BS-77 framework. Extensive tables of numerical data and several maps of coverage areas are provided.

  2. Downlinks for DBS - Design and engineering considerations

    NASA Astrophysics Data System (ADS)

    Blecker, M.; Martin, E. R.

    1985-01-01

    The subsystem interrelationships and design parameters choice procedures for a DBS downlink design are discussed from a business decisions point of view. The image quality is determined by customer satisfaction, which is translated to a required carrier/noise (C/N) ratio. The C/N ratio defines acceptable levels of signal fading, a subjective value which is modified by the demographics of the service area. Increasing the satellite on-board transmitting power to meet acceptable broadcast reliability places burdens on the start-up capitalization of the business. Larger receiving antennas in rural areas ameliorates some of the power requirements. The dish size, however, affects the labor costs of installation, but must be kept small enough to be used in heavily populated areas. The satellites must be built, as far as is possible, from off-the-shelf components to keep costs down. Design selections for a sample complete system are listed.

  3. Patient-Specific Model-Based Investigation of Speech Intelligibility and Movement during Deep Brain Stimulation

    PubMed Central

    Åström, Mattias; Tripoliti, Elina; Hariz, Marwan I.; Zrinzo, Ludvic U.; Martinez-Torres, Irene; Limousin, Patricia; Wårdell, Karin

    2010-01-01

    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 anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus. PMID:20460952

  4. Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes

    NASA Astrophysics Data System (ADS)

    Boinagrov, David; Pangratz-Fuehrer, Susanne; Goetz, Georges; Palanker, Daniel

    2014-04-01

    Objective. Intra-retinal placement of stimulating electrodes can provide close and stable proximity to target neurons. We assessed improvement in stimulation thresholds and selectivity of the direct and network-mediated retinal stimulation with intraretinal electrodes, compared to epiretinal and subretinal placements. Approach. Stimulation thresholds of the retinal ganglion cells (RGCs) in wild-type rat retina were measured using the patch-clamp technique. Direct and network-mediated responses were discriminated using various synaptic blockers. Main results. Three types of RGC responses were identified: short latency (SL, τ < 5 ms) originating in RGCs, medium latency (ML, 3 < τ < 70 ms) originating in the inner nuclear layer and long latency (LL, τ > 40 ms) originating in photoreceptors. Cathodic epiretinal stimulation exhibited the lowest threshold for direct RGC response and the highest direct selectivity (network/direct thresholds ratio), exceeding a factor of 3 with pulse durations below 0.5 ms. For network-mediated stimulation, the lowest threshold was obtained with anodic pulses in OPL position, and its network selectivity (direct/network thresholds ratio) increased with pulse duration, exceeding a factor of 4 at 10 ms. Latency of all three types of responses decreased with increasing strength of the stimulus. Significance. These results define the optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs.

  5. Intraoperative MR-guided DBS implantation for treating PD and ET

    NASA Astrophysics Data System (ADS)

    Liu, Haiying; Maxwell, Robert E.; Truwit, Charles L.

    2001-05-01

    Deep brain stimulator (DBS) implantation is a promising treatment alternative for suppressing the motor tremor symptoms in Parkinson disease (PD) patient. The main objective is to develop a minimally invasive approach using high spatial resolution and soft-tissue contrast MR imaging techniques to guide the surgical placement of DBS. In the MR-guided procedure, the high spatial resolution MR images were obtained intra-operatively and used to target stereotactically a specific deep brain location. The neurosurgery for craniotomy was performed in the front of the magnet outside of the 10 Gauss line. Aided with positional registration assembly for the stereotactic head frame, the target location (VIM or GPi or STN) in deep brain areas was identified and measured from the MR images in reference to the markers in the calibration assembly of the head frame before the burrhole prep. In 20 patients, MR- guided DBS implantations have been performed according to the new methodology. MR-guided DBS implantation at high magnetic field strength has been shown to be feasible and desirable. In addition to the improved outcome, this offers a new surgical approach in which intra-operative visualization is possible during intervention, and any complications such as bleeding can be assessed in situ immediately prior to dural closure.

  6. Sputtered iridium oxide films (SIROFs) for low-impedance neural stimulation and recording electrodes.

    PubMed

    Cogan, S F; Plante, T D; Ehrlich, J

    2004-01-01

    Iridium oxide films formed by electrochemical activation of iridium metal (AIROF) or by electrochemical deposition (EIROF) are being evaluated as low-impedance charge-injection coatings for neural stimulation and recording. Iridium oxide may also be deposited by reactive sputtering from iridium metal in an oxidizing plasma. The characterization of sputtered iridium oxide films (SIROFs) as coatings for nerve electrodes is reported. SIROFs were characterized by cyclic voltammetry, electrochemical impedance spectroscopy, and potential transient measurements during charge-injection. The surface morphology of the SIROF transitions from smooth to highly nodular with increasing film thickness from 80 nm to 4600 nm. Charge-injection capacities exceed 0.75 mC/cm(2) with 0.75 ms current pulses in thicker films. The SIROF was deposited on both planar and non-planar substrates and photolithographically patterned by lift-off.

  7. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

    PubMed

    Perez-Caballero, L; Pérez-Egea, R; Romero-Grimaldi, C; Puigdemont, D; Molet, J; Caso, J-R; Mico, J-A; Pérez, V; Leza, J-C; Berrocoso, E

    2014-05-01

    Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

  8. Deep brain stimulation for movement disorders.

    PubMed

    Larson, Paul S

    2014-07-01

    Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.

  9. In vitro extracellular recording and stimulation performance of nanoporous gold-modified multi-electrode arrays

    NASA Astrophysics Data System (ADS)

    Kim, Yong Hee; Kim, Gook Hwa; Kim, Ah Young; Han, Young Hwan; Chung, Myung-Ae; Jung, Sang-Don

    2015-12-01

    Objective. Nanoporous gold (Au) structures can reduce the impedance and enhance the charge injection capability of multi-electrode arrays (MEAs) used for interfacing neuronal networks. Even though there are various nanoporous Au preparation techniques, fabrication of MEA based on low-cost electro-codeposition of Ag:Au has not been performed. In this work, we have modified a Au MEA via the electro-codeposition of Ag:Au alloy, followed by the chemical etching of Ag, and report on the in vitro extracellular recording and stimulation performance of the nanoporous Au-modified MEA. Approach. Ag:Au alloy was electro-codeposited on a bilayer lift-off resist sputter-deposition passivated Au MEA followed by chemical etching of Ag to form a porous Au structure. Main results. The porous Au structure was analyzed by scanning electron microscopy and tunneling electron microscopy and found to have an interconnected nanoporous Au structure. The impedance value of the nanoporous Au-modified MEA is 15.4 ± 0.55 kΩ at 1 kHz, accompanied by the base noise V rms of 2.4 ± 0.3 μV. The charge injection limit of the nanoporous Au-modified electrode estimated from voltage transient measurement is approximately 1 mC cm-2, which is comparable to roughened platinum and carbon nanotube electrodes. The charge injection capability of the nanoporous Au-modified MEA was confirmed by observing stimulus-induced spikes at above 0.2 V. The nanoporous Au-modified MEA showed mechanical durability upon ultrasonic treatment for up to an hour. Significance. Electro-codeposition of Ag:Au alloy combined with chemical etching Ag is a low-cost process for fabricating nanoporous Au-modified MEA suitable for establishing the stimulus-response relationship of cultured neuronal networks.

  10. Deep Brain Stimulation in Anorexia Nervosa: Hope for the Hopeless or Exploitation of the Vulnerable? The Oxford Neuroethics Gold Standard Framework.

    PubMed

    Park, Rebecca J; Singh, Ilina; Pike, Alexandra C; Tan, Jacinta O A

    2017-01-01

    Neurosurgical interventions for psychiatric disorders have a long and troubled history (1, 2) but have become much more refined in the last few decades due to the rapid development of neuroimaging and robotic technologies (2). These advances have enabled the design of less invasive techniques, which are more focused, such as deep brain stimulation (DBS) (3). DBS involves electrode insertion into specific neural targets implicated in pathological behavior, which are then repeatedly stimulated at adjustable frequencies. DBS has been used for Parkinson's disease and movement disorders since the 1960s (4-6) and over the last decade has been applied to treatment-refractory psychiatric disorders, with some evidence of benefit in obsessive-compulsive disorder (OCD), major depressive disorder, and addictions (7). Recent consensus guidelines on best practice in psychiatric neurosurgery (8) stress, however, that DBS for psychiatric disorders remains at an experimental and exploratory stage. The ethics of DBS-in particular for psychiatric conditions-is debated (1, 8-10). Much of this discourse surrounds the philosophical implications of competence, authenticity, personality, or identity change following neurosurgical interventions, but there is a paucity of applied guidance on neuroethical best practice in psychiatric DBS, and health-care professionals have expressed that they require more (11). This paper aims to redress this balance by providing a practical, applied neuroethical gold standard framework to guide research ethics committees, researchers, and institutional sponsors. We will describe this as applied to our protocol for a particular research trial of DBS in severe and enduring anorexia nervosa (SE-AN) (https://clinicaltrials.gov/ct2/show/NCT01924598, unique identifier NCT01924598), but believe it may have wider application to DBS in other psychiatric disorders.

  11. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression.

  12. [Twiddler's syndrome in a patient with obsessive-compulsive disorder treated with deep brain stimulation].

    PubMed

    Moliz, Nicolás; Katati, Majed J; Iañez, Benjamín; García, Asunción; Yagui, Eskandar; Horcajadas, Ángel

    2015-01-01

    Twiddler's syndrome is a rare complication associated with implantable electrical stimulation devices. First described in a patient with a pacemaker, it is a known complication in the field of cardiology. However, it is not so recognised in the world of neurosurgery, in which it has been described in relation to deep brain stimulation (DBS) devices. Characterised by manipulating either consciously or unconsciously the generator of such devices, which causes it to rotate on itself, the syndrome causes the coiling of the wiring of these systems and can lead to their rupture or the displacement of intracranial electrodes. We describe a case of twiddler's syndrome in a patient treated with DBS for obsessive-compulsive disorder, in which clinical deterioration presented after a good initial response. Control radiographs revealed rotation of the wiring system and displacement of the intracranial electrodes.

  13. The effect of inter-electrode distance on the electric field distribution during transcutaneous lumbar spinal cord direct current stimulation.

    PubMed

    Bastos, Rui; Fernandes, Sofia R; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede A; Miranda, Pedro C; Bastos, Rui; Fernandes, Sofia R; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede A; Miranda, Pedro C; Miranda, Pedro C; Bastos, Rui; Wenger, Cornelia; Salvador, Ricardo; de Carvalho, Mamede A; Fernandes, Sofia R

    2016-08-01

    Previous studies have indicated potential neuromodulation of the spinal circuitry by transcutaneous spinal direct current stimulation (tsDCS), such as changes in motor unit recruitment, shortening of the peripheral silent period and interference with supraspinal input to lower motor neurons. All of these effects were dependent on the polarity of the electrodes. The present study investigates how the distance between the electrodes during tsDCS influences the electric field's (E-field) spatial distribution in the lumbar and sacral spinal cord (SC). The electrodes were placed longitudinally along the SC, with the target electrode over the lumbar spine, and the return electrode above the former, considering four different distances (4, 8, 12 and 16 cm from the target). A fifth configuration was also tested with the return electrode over the right deltoid muscle. Peak values of the E-field's magnitude are found in the lumbo-sacral region of the SC for all tested configurations. Increasing the distance between the electrodes results in a wider spread of the E-field magnitude distribution along the SC, with larger maximum peak values and a smoother variation. The fifth configuration does not present the highest maximum values when compared to the other configurations. The results indicate that the choice of the return electrode position relative to the target can influence the distribution and the range of values of the E-field magnitude in the SC. Possible clinical significance of the observed effects will be discussed.

  14. Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

    PubMed Central

    Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

    2016-01-01

    Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

  15. The effect of cystic cavities on deep brain stimulation in the basal ganglia: a simulation-based study

    NASA Astrophysics Data System (ADS)

    Åström, Mattias; Johansson, Johannes D.; Hariz, Marwan I.; Eriksson, Ola; Wårdell, Karin

    2006-06-01

    Although the therapeutic effect of deep brain stimulation (DBS) is well recognized, a fundamental understanding of the mechanisms responsible is still not known. In this study finite element method (FEM) modelling and simulation was used in order to study relative changes of the electrical field extension surrounding a monopolar DBS electrode positioned in grey matter. Due to the frequently appearing cystic cavities in the DBS-target globus pallidus internus, a nucleus of grey matter with and without a cerebrospinal fluid filled cystic cavity was modelled. The position, size and shape of the cyst were altered in relation to the electrode. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between grey and white matters. The cyst increased the radial extension and changed the shape of the electrical field substantially. The position, size and shape of the cyst were the main influencing factors. We suggest that cystic cavities in the DBS-target may result in closely related unexpected structures or neural fibre bundles being stimulated and could be one of the reasons for suboptimal clinical effects or stimulation-induced side effects.

  16. [Early Experience with the VerciseTM DBS System in the Treatment of Dystonic Tremor].

    PubMed

    Miyagi, Yasushi

    2017-03-01

    Six cases of dystonic tremor were treated with the VerciseTM deep brain stimulation(DBS)system, which has the multiple independent current control(MICC)technology. The mean preoperative score of Burke-Fahn-Marsden dystonia rating scale was 16.2±9.4, which was reduced to 6.1±4.6 at 5 months postoperatively. A 65-year-old male presented an intractable dystonic tremor of the jaw, neck, and shoulders due to tardive syndrome. He experienced the successful tremor relief after unipolar DBS in the globus pallidus internus(GPi)with VerciseTM but complained of dysarthria. Steering the current ventrally induced nausea without alleviating dysarthria, while steering the current dorsally alleviated dysarthria but a further dorsal current induced mandibular dyskinesia. The current steering with MICC enabled the simulation field in GPi with successful balance, maximizing tremor suppression, and minimizing the adverse effects. In a second case, 61-year-old male in whom cervical dystonia with rotatory tremor had been successfully treated with interleaving stimulation of GPi-DBS had needed to repeat the replacement of a non-rechargeable pulse generator in only 15-month interval. After the substitution of VerciseTM, the interleaving stimulation of 9.5mA in total was replaced by 8.5mA with the current steering of MICC, while the patient's symptomatic control was unchanged. The microlesion effects after lead implantation are unclear and therapeutic effects are often delayed in cases of dystonia;therefore, the submaximal stimulation intensities must be frequently applied in the early phase following the implantation of DBS. A fine current steering of VerciseTM DBS is very useful in both, the early and late phases of GPi-DBS for dystonic syndrome.

  17. Control of Dynamic Limb Motion Using Fatigue-Resistant Asynchronous Intrafascicular Multi-Electrode Stimulation

    PubMed Central

    Frankel, Mitchell A.; Mathews, V John; Clark, Gregory A.; Normann, Richard A.; Meek, Sanford G.

    2016-01-01

    Asynchronous intrafascicular multi-electrode stimulation (aIFMS) of small independent populations of peripheral nerve motor axons can evoke selective, fatigue-resistant muscle forces. We previously developed a real-time proportional closed-loop control method for aIFMS generation of isometric muscle force and the present work extends and adapts this closed-loop controller to the more demanding task of dynamically controlling joint position in the presence of opposing joint torque. A proportional-integral-velocity controller, with integrator anti-windup strategies, was experimentally validated as a means to evoke motion about the hind-limb ankle joint of an anesthetized feline via aIFMS stimulation of fast-twitch plantar-flexor muscles. The controller was successful in evoking steps in joint position with 2.4% overshoot, 2.3-s rise time, 4.5-s settling time, and near-zero steady-state error. Controlled step responses were consistent across changes in step size, stable against external disturbances, and reliable over time. The controller was able to evoke smooth eccentric motion at joint velocities up to 8 deg./s, as well as sinusoidal trajectories with frequencies up to 0.1 Hz, with time delays less than 1.5 s. These experiments provide important insights toward creating a robust closed-loop aIFMS controller that can evoke precise fatigue-resistant motion in paralyzed individuals, despite the complexities introduced by aIFMS. PMID:27679557

  18. A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

    PubMed Central

    Mace, Michael; Pavese, Nicola; Borisyuk, Roman; Bain, Peter

    2017-01-01

    Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit. PMID:28068428

  19. Probing the Human Brain with Stimulating Electrodes: The Story of Roberts Bartholow's (1874) Experiment on Mary Rafferty

    ERIC Educational Resources Information Center

    Harris, Lauren Julius; Almerigi, Jason B.

    2009-01-01

    Roberts Bartholow's 1874 experiment on Mary Rafferty is widely cited as the first demonstration, by direct application of stimulating electrodes, of the motor excitability of the human cerebral cortex. The many accounts of the experiment, however, leave certain questions and details unexamined or unresolved, especially about Bartholow's goals, the…

  20. Deep brain stimulation of the nucleus accumbens shell attenuates cue-induced reinstatement of both cocaine and sucrose seeking in rats.

    PubMed

    Guercio, Leonardo A; Schmidt, Heath D; Pierce, R Christopher

    2015-03-15

    Stimuli previously associated with drug taking can become triggers that can elicit craving and lead to relapse of drug-seeking behavior. Here, we examined the influence of deep brain stimulation (DBS) in the nucleus accumbens shell on cue-induced reinstatement of cocaine seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.254 mg, i.v.) for 2 h daily for 21 days, with each infusion of cocaine being paired with a cue light. After 21 days of self-administration, cocaine-taking behavior was extinguished by replacing cocaine with saline in the absence of the cue light. Next, during the reinstatement phase, DBS was administered bilaterally into the nucleus accumbens shell through bipolar stainless steel electrodes immediately prior to re-exposure to cues previously associated with cocaine reinforcement. DBS continued throughout the 2 h reinstatement session. Parallel studies examined the influence of accumbens shell DBS on reinstatement induced by cues previously associated with sucrose reinforcement. Results indicated that DBS of the nucleus accumbens shell significantly attenuated cue-induced reinstatement of cocaine and sucrose seeking. Together, these results indicate that DBS of the accumbens shell disrupts cue-induced reinstatement associated with both a drug and a natural reinforcer.

  1. The effects of DBS patterns on basal ganglia activity and thalamic relay : a computational study.

    PubMed

    Agarwal, Rahul; Sarma, Sridevi V

    2012-08-01

    Thalamic neurons receive inputs from cortex and their responses are modulated by the basal ganglia (BG). This modulation is necessary to properly relay cortical inputs back to cortex and downstream to the brain stem when movements are planned. In Parkinson's disease (PD), the BG input to thalamus becomes pathological and relay of motor-related cortical inputs is compromised, thereby impairing movements. However, high frequency (HF) deep brain stimulation (DBS) may be used to restore relay reliability, thereby restoring movements in PD patients. Although therapeutic, HF stimulation consumes significant power forcing surgical battery replacements, and may cause adverse side effects. Here, we used a biophysical-based model of the BG-Thalamus motor loop in both healthy and PD conditions to assess whether low frequency stimulation can suppress pathological activity in PD and enable the thalamus to reliably relay movement-related cortical inputs. We administered periodic pulse train DBS waveforms to the sub-thalamic nucleus (STN) with frequencies ranging from 0-140 Hz, and computed statistics that quantified pathological bursting, oscillations, and synchronization in the BG as well as thalamic relay of cortical inputs. We found that none of the frequencies suppressed all pathological activity in BG, though the HF waveforms recovered thalamic reliability. Our rigorous study, however, led us to a novel DBS strategy involving low frequency multi-input phase-shifted DBS, which successfully suppressed pathological symptoms in all BG nuclei and enabled reliable thalamic relay. The neural restoration remained robust to changes in the model parameters characterizing early to late PD stages.

  2. Comparison of Proximally Versus Distally Placed Spatially Distributed Sequential Stimulation Electrodes in a Dynamic Knee Extension Task.

    PubMed

    Laubacher, Marco; Aksöz, Efe A; Binder-Macleod, Stuart; Hunt, Kenneth J

    2016-06-13

    Spatially distributed sequential stimulation (SDSS) has demonstrated substantial power output and fatigue benefits compared to single electrode stimulation (SES) in the application of functional electrical stimulation (FES). This asymmetric electrode setup brings new possibilities but also new questions since precise placement of the electrodes is one critical factor for good muscle activation. The aim of this study was to compare the power output, fatigue and activation properties of proximally versus distally placed SDSS electrodes in an isokinetic knee extension task simulating knee movement during recumbent cycling. M. vastus lateralis and medialis of seven able-bodied subjects were stimulated with rectangular bi-phasic pulses of constant amplitude of 40 mA and at an SDSS frequency of 35 Hz for 6 min on both legs with both setups (i.e. n=14). Torque was measured during knee-extension movement by a dynamometer at an angular velocity of 110 deg/s. Mean power, peak power and activation time were calculated and compared for the initial and final stimulation phases, together with an overall fatigue index. Power output values (Pmean, Ppeak) were scaled to a standardised reference input pulse width of 100 μs (Pmean,s, Ppeak,s). The initial evaluation phase showed no significant differences between the two setups for all outcome measures. Ppeak and Ppeak,s were both significantly higher in the final phase for the distal setup (25.4 ± 8.1 W vs. 28.2 ± 6.2 W, p=0.0062 and 34.8 ± 9.5 W vs. 38.9 ± 6.7 W, p=0.021, respectively). With distal SDSS, there was modest evidence of higher Pmean and Pmean,s (p=0.071, p=0.14, respectively) but of longer activation time (p=0.096). The rate of fatigue was similar for both setups. For practical FES applications, distal placement of the SDSS electrodes is preferable.

  3. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

    PubMed

    Schlaepfer, Thomas E; Cohen, Michael X; Frick, Caroline; Kosel, Markus; Brodesser, Daniela; Axmacher, Nikolai; Joe, Alexius Young; Kreft, Martina; Lenartz, Doris; Sturm, Volker

    2008-01-01

    Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.

  4. Effects of deep brain stimulation and medication on bradykinesia and muscle activation in Parkinson's disease.

    PubMed

    Vaillancourt, David E; Prodoehl, Janey; Verhagen Metman, Leo; Bakay, Roy A; Corcos, Daniel M

    2004-03-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and antiparkinsonian medication (Meds) have proved to be effective therapies for treating bradykinesia in Parkinson's disease. However, it is not currently known how or to what extent STN stimulation alters the control signals to agonist and antagonist muscles to change movement speed. Our objective was to investigate movement speed along with the amplitude and temporal features of EMG activity to determine how and to what extent these parameters are changed by DBS and medication. Nine patients with Parkinson's disease were studied following neurosurgery that implanted high-frequency stimulating electrodes in the STN. The experiments for the patients were performed in each of four treatment conditions: (i) OFF treatment; (ii) STN DBS; (iii) Meds; and (iv) Meds plus STN DBS. Also, a group of age- and gender-matched control subjects were examined. Medication and DBS had similar effects in that both treatments increased movement speed, increased the amplitude of the first agonist burst, increased burst duration, reduced the number of agonist bursts, reduced cocontraction, increased the size of the antagonist EMG, and reduced the centroid time of the antagonist EMG. When DBS and medication were combined, only temporal measures of burst duration and the number of agonist bursts were different from the medication alone condition. There was a positive association between the level of bradykinesia OFF treatment and the level of bradykinesia following DBS and medication. The movement speed of neurologically normal control subjects' was over 40% higher during both flexion and extension movements when compared with the patients during Meds plus STN DBS. The changes in the muscle activation patterns provide a mechanism of action for the pharmacological and surgical interventions used to treat bradykinesia in Parkinson's disease. However, despite the success of medication and DBS at improving bradykinesia in patients

  5. Clinical application of peroneal nerve stimulator system using percutaneous intramuscular electrodes for correction of foot drop in hemiplegic patients.

    PubMed

    Shimada, Yoichi; Matsunaga, Toshiki; Misawa, Akiko; Ando, Shigeru; Itoi, Eiji; Konishi, Natsuo

    2006-10-01

    Objective.  To assess the orthotic effect of a functional electrical stimulation device (Akita Heel Sensor System; AHSS) in the treatment of hemiplegic gait with foot drop. Materials and Methods.  In the AHSS, a heel sensor is attached to a small plastic heel brace, and the peroneal nerve is stimulated via percutaneous intramuscular electrodes. During the swing phase of the hemiplegic gait, the common peroneal nerve is stimulated by the AHSS. Eight patients in chronic stages of hemiplegia participated in this study. Walking speeds and step cadences on a 10-m course were compared between walking with stimulation and walking without stimulation. Results.  Mean walking speed (± SD) was 0.50 ± 0.26 m/sec without stimulation and 0.64 ± 0.31 m/sec with stimulation. The mean percentage increase in walking speed with stimulation was 30.1%. Mean step cadence was 31 ± 7 steps/10 m without stimulation and 27 ± 7 steps/10 m with stimulation. By correcting foot drop, the AHSS significantly increased walking speed and decreased cadence (p < 0.05). Conclusion.  The AHSS can significantly improve walking in hemiplegic patients with foot drop.

  6. Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior.

    PubMed

    Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Ami-Ad, Lavi; Yaka, Rami; Yadid, Gal

    2010-11-01

    The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25-1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5-20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABA(A)β, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA.

  7. Automatic trajectory planning of DBS neurosurgery from multi-modal MRI datasets.

    PubMed

    Bériault, Silvain; Al Subaie, Fahd; Mok, Kelvin; Sadikot, Abbas F; Pike, G Bruce

    2011-01-01

    We propose an automated method for preoperative trajectory planning of deep brain stimulation image-guided neurosurgery. Our framework integrates multi-modal MRI analysis (T1w, SWI, TOF-MRA) to determine an optimal trajectory to DBS targets (subthalamic nuclei and globus pallidus interna) while avoiding critical brain structures for prevention of hemorrhages, loss of function and other complications. Results show that our method is well suited to aggregate many surgical constraints and allows the analysis of thousands of trajectories in less than 1/10th of the time for manual planning. Finally, a qualitative evaluation of computed trajectories resulted in the identification of potential new constraints, which are not addressed in the current literature, to better mimic the decision-making of the neurosurgeon during DBS planning.

  8. Electrical Stimulation of NIH-3T3 Cells with Platinum-PEDOT-Electrodes Integrated in a Bioreactor

    PubMed Central

    Blume, Grit; Müller-Wichards, Wiebke; Goepfert, Christiane; Pörtner, Ralf; Müller, Jörg

    2013-01-01

    The objective of this work involves the development and integration of electrodes for the electrical stimulation of cells within a bioreactor. Electrodes need to fit properties such as biocompatibility, large reversible charge transfer and high flexibility in view of their future application as implants on the tympanic membrane. Flexible thin-film platinum-poly(3,4-ethylene-dioxythiophene)-electrodes on a poly(ethylene terephthalate)-foil manufactured using microsystems technology were integrated into a bioreactor based on the design of a 24 well plate. The murine fibroblast cell line NIH-3T3 was cultured on the foil electrodes and the cells were stimulated with direct voltage and unipolar pulsed voltage. The amplitude, the pulse length and the ratio of pulse to pause were varied. The stimulated cells were stained in order to determine the angle between the cell cleavage plane of the dividing cells and the vector of the electric field. These angles were subsequently used to calculate the polarization index, which is a measure of the orientation of the metaphase plane of dividing cells that occurs for example during wound healing or embryonic morphogenesis. PMID:24358059

  9. Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation

    PubMed Central

    Settell, Megan L.; Testini, Paola; Cho, Shinho; Lee, Jannifer H.; Blaha, Charles D.; Jo, Hang J.; Lee, Kendall H.; Min, Hoon-Ki

    2017-01-01

    Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI). Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V). Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected < 0.001). During neurochemical measurements, stimulation time-locked changes in dopamine release were recorded in the NAc, confirming that mesolimbic dopaminergic neurons were stimulated by DBS. In the

  10. Chronic stress-like syndrome as a consequence of medial site subthalamic stimulation in Parkinson's disease.

    PubMed

    Růžička, Filip; Jech, Robert; Nováková, Lucie; Urgošík, Dušan; Bezdíček, Ondřej; Vymazal, Josef; Růžička, Evžen

    2015-02-01

    Considering the functional organization of the subthalamic nucleus (STN), we hypothesized that subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease might have a differential impact on the hypothalamic-pituitary-adrenal axis in relation to the position of active stimulating contact within the STN. In addition, we searched for any STN-DBS-related morning plasma cortisol changes in association with postoperative anxiety and weight gain. A plasma cortisol measurement was performed on the day of initiation of bilateral STN-DBS and repeated after 1 and 17 months in twenty patients with advanced Parkinson's disease. The body weight change and anxiety scores following the implantation were assessed as well. The electrode positions in the STN were determined on T1-weighted magnetic resonance images. After initiation of stimulation, cortisol levels significantly decreased and the cortisol changes after 1 and 17 months strongly correlated with the position of active contact in the subthalamic area. Patients with at least one contact located more medially in the STN experienced a significantly greater decrease of cortisol than those with one or both active contacts more laterally. Furthermore, the lower cortisol levels were strongly associated with higher trait anxiety and weight gain. These changes mimicked the effects of chronic stress and suggest the disturbing impact of STN-DBS on limbic and motivational systems.

  11. Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments.

    PubMed

    Mahlknecht, Philipp; Limousin, Patricia; Foltynie, Thomas

    2015-11-01

    Modern deep brain stimulation (DBS) has become a routine therapy for patients with movement disorders such as Parkinson's disease, generalized or segmental dystonia and for multiple forms of tremor. Growing numbers of publications also report beneficial effects in other movement disorders such as Tourette's syndrome, various forms of chorea and DBS is even being studied for Parkinson's-related dementia. While exerting remarkable effects on many motor symptoms, DBS does not restore normal neurophysiology and therefore may also have undesirable side effects including speech and gait deterioration. Furthermore, its efficacy might be compromised in the long term, due to progression of the underlying disease. Various programming strategies have been studied to try and address these issues, e.g., the use of low-frequency rather than high-frequency stimulation or the targeting of alternative brain structures such as the pedunculopontine nucleus. In addition, further technical developments will soon provide clinicians with an expanded choice of hardware such as segmented electrodes allowing for a steering of the current to optimize beneficial effects and reduce side effects as well as the possibility of adaptive stimulation systems based on closed-loop concepts with or without accompanying advances in programming and imaging software. In the present article, we will provide an update on the most recent achievements and discoveries relevant to the application of DBS in the treatment of movement disorder patients and give an outlook on future clinical and technical developments.

  12. Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes

    PubMed Central

    Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L.; Kay, Steven M.; Besio, Walter G.

    2012-01-01

    Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback. PMID:22772373

  13. Electrical resistance increases at the tissue-electrode interface as an early response to nucleus accumbens deep brain stimulation.

    PubMed

    Kale, Rajas P; Kouzani, Abbas Z; Berk, Julian; Walder, Ken; Berk, Michael; Tye, Susannah J

    2016-08-01

    The therapeutic actions of deep brain stimulation are not fully understood. The early inflammatory response of electrode implantation is associated with symptom relief without electrical stimulation, but is negated by anti-inflammatory drugs. Early excitotoxic necrosis and subsequent glial scarring modulate the conductivity of the tissue-electrode interface, which can provide some detail into the inflammatory response of individual patients. The feasibility of this was demonstrated by measuring resistance values across a bipolar electrode which was unilaterally implanted into the nucleus accumbens of a rat while receiving continuous deep brain stimulation with a portable back-mounted device using clinical parameters (130Hz, 200μA, 90μs) for 3 days. Daily resistance values rose significantly (p<;0.0001), while hourly resistance analysis demonstrated a plateau after an initial spike in resistance, which was then followed by a steady increase (p<;0.05; p<;0.0001). We discuss that the biphasic nature of the inflammatory response may contribute to these observations and conclude that this method may translate to a safe predictive screening for more effective clinical deep brain stimulation.

  14. High-Frequency Stimulation of the Subthalamic Nucleus Restores Neural and Behavioral Functions During Reaction Time Task in a Rat Model of Parkinson’s Disease

    PubMed Central

    Li, Xiang-Hong; Wang, Jin-Yan; Gao, Ge; Chang, Jing-Yu; Woodward, Donald J.; Luo, Fei

    2015-01-01

    Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson’s disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating corticobasal ganglia circuits. PMID:20025062

  15. Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient.

    PubMed

    Herron, Jeffrey A; Thompson, Margaret C; Brown, Timothy; Chizeck, Howard J; Ojemann, Jeffrey G; Ko, Andrew L

    2016-11-18

    Deep brain stimulation (DBS) has become a widespread and valuable treatment for patients with movement disorders such as essential tremor (ET). However, current DBS treatment constantly delivers stimulation in an open loop, which can be inefficient. Closing the loop with sensors to provide feedback may increase power efficiency and reduce side effects for patients. New implantable neuromodulation platforms, such as the Medtronic Activa PC+S DBS system, offer important data sources by providing chronic neural sensing capabilities and a means of investigating dynamic stimulation based on symptom measurements. The authors implanted in a single patient with ET an Activa PC+S system, a cortical strip of electrodes on the hand sensorimotor cortex, and therapeutic electrodes in the ventral intermediate nucleus of the thalamus. In this paper they describe the effectiveness of the platform when sensing cortical movement intentions while the patient actually performed and imagined performing movements. Additionally, they demonstrate dynamic closed-loop DBS based on several wearable sensor measurements of tremor intensity.

  16. Electrode

    SciTech Connect

    Clere, T.M.

    1983-08-30

    A 3-dimensional electrode is disclosed having substantially coplanar and substantially flat portions and ribbon-like curved portions, said curved portions being symmetrical and alternating in rows above and below said substantially coplanar, substantially flat portions, respectively, and a geometric configuration presenting in one sectional aspect the appearance of a series of ribbon-like oblate spheroids interrupted by said flat portions and in another sectional aspect, 90/sup 0/ from said one aspect, the appearance of a square wave pattern.

  17. EEG power asymmetry and functional connectivity as a marker of treatment effectiveness in DBS surgery for depression.

    PubMed

    Quraan, Maher A; Protzner, Andrea B; Daskalakis, Zafiris J; Giacobbe, Peter; Tang, Chris W; Kennedy, Sidney H; Lozano, Andres M; McAndrews, Mary P

    2014-04-01

    Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatment-resistant depression. Although there have been encouraging results in open-label trials, about half of the patients fail to achieve meaningful benefit. Although progress has been made in understanding the neurobiology of MDD, the ability to characterize differences in brain dynamics between those who do and do not benefit from DBS is lacking. In this study, we investigated EEG resting-state data recorded from 12 patients that have undergone DBS surgery. Of those, six patients were classified as responders to DBS, defined as an improvement of 50% or more on the 17-item Hamilton Rating Scale for Depression (HAMD-17). We compared hemispheric frontal theta and parietal alpha power asymmetry and synchronization asymmetry between responders and non-responders. Hemispheric power asymmetry showed statistically significant differences between responders and non-responders with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry was characterized by an increase in frontal theta in the right hemisphere relative to the left combined with an increase in parietal alpha in the left hemisphere relative to the right in non-responders compared with responders. Hemispheric mean synchronization asymmetry showed a statistically significant difference between responders and non-responders in the theta band, with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry resulted from an increase in frontal synchronization in the right hemisphere relative to the left combined with an increase in parietal synchronization in the left hemisphere relative to the right in non-responders compared with responders. Connectivity diagrams revealed long-range differences in frontal/central-parietal connectivity between the two groups in the theta band. This pattern was observed irrespective of

  18. Direct broadcast satellite (DBS) in the United States

    NASA Astrophysics Data System (ADS)

    Alpert, Michael S.

    1991-11-01

    DBS technologies are reviewed with specific reference to its recent dormancy, present heightened activity level, and its implications for industries such as information, broadcasting, and entertainment. The differences between low-, medium-, and high-power satellites are identified, and the key U.S. entities are listed in terms of DBS development and implementation. The main industry players include COMSAT's subsidiary Satellite Television Corporation, the Direct Broadcast Satellite Corporation, Dominion, and Hubbard USSB. The lack of activity in the 1980s is related to the investment profile of DBS, deflation related to larger companies which participated only briefly, unreliable technologies, and interruption by the cable industry. The importance of DBS technologies to economic expansion is underscored particulary for entertainment and information programming.

  19. Optimizing the delivery of deep brain stimulation using electrophysiological atlases and an inverse modeling approach

    NASA Astrophysics Data System (ADS)

    Sun, Kay; Pallavaram, Srivatsan; Rodriguez, William; D'Haese, Pierre-Francois; Dawant, Benoit M.; Miga, Michael I.

    2012-02-01

    The use of deep brain stimulation (DBS) for the treatment of neurological movement degenerative disorders requires the precise placement of the stimulating electrode and the determination of optimal stimulation parameters that maximize symptom relief (e.g. tremor, rigidity, movement difficulties, etc.) while minimizing undesired physiological side-effects. This study demonstrates the feasibility of determining the ideal electrode placement and stimulation current amplitude by performing a patient-specific multivariate optimization using electrophysiological atlases and a bioelectric finite element model of the brain. Using one clinical case as a preliminary test, the optimization routine is able to find the most efficacious electrode location while avoiding the high side-effect regions. Future work involves optimization validation clinically and improvement to the accuracy of the model.

  20. Delayed and lasting effects of deep brain stimulation on locomotion in Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Beuter, Anne; Modolo, Julien

    2009-06-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by a variety of motor signs affecting gait, postural stability, and tremor. These symptoms can be improved when electrodes are implanted in deep brain structures and electrical stimulation is delivered chronically at high frequency (>100 Hz). Deep brain stimulation (DBS) onset or cessation affects PD signs with different latencies, and the long-term improvements of symptoms affecting the body axis and those affecting the limbs vary in duration. Interestingly, these effects have not been systematically analyzed and modeled. We compare these timing phenomena in relation to one axial (i.e., locomotion) and one distal (i.e., tremor) signs. We suggest that during DBS, these symptoms are improved by different network mechanisms operating at multiple time scales. Locomotion improvement may involve a delayed plastic reorganization, which takes hours to develop, whereas rest tremor is probably alleviated by an almost instantaneous desynchronization of neural activity in subcortical structures. Even if all PD patients develop both distal and axial symptoms sooner or later, current computational models of locomotion and rest tremor are separate. Furthermore, a few computational models of locomotion focus on PD and none exploring the effect of DBS was found in the literature. We, therefore, discuss a model of a neuronal network during DBS, general enough to explore the subcircuits controlling locomotion and rest tremor simultaneously. This model accounts for synchronization and plasticity, two mechanisms that are believed to underlie the two types of symptoms analyzed. We suggest that a hysteretic effect caused by DBS-induced plasticity and synchronization modulation contributes to the different therapeutic latencies observed. Such a comprehensive, generic computational model of DBS effects, incorporating these timing phenomena, should assist in developing a more efficient, faster, durable treatment of

  1. Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording.

    PubMed

    Lai, Hsin-Yi; Liao, Lun-De; Lin, Chin-Teng; Hsu, Jui-Hsiang; He, Xin; Chen, You-Yin; Chang, Jyh-Yeong; Chen, Hui-Fen; Tsang, Siny; Shih, Yen-Yu I

    2012-06-01

    An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 µm thick and with a diameter of 16 µm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.

  2. Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording

    NASA Astrophysics Data System (ADS)

    Lai, Hsin-Yi; Liao, Lun-De; Lin, Chin-Teng; Hsu, Jui-Hsiang; He, Xin; Chen, You-Yin; Chang, Jyh-Yeong; Chen, Hui-Fen; Tsang, Siny; Shih, Yen-Yu I.

    2012-06-01

    An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 µm thick and with a diameter of 16 µm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.

  3. Deep Brain Stimulation in Anorexia Nervosa: Hope for the Hopeless or Exploitation of the Vulnerable? The Oxford Neuroethics Gold Standard Framework

    PubMed Central

    Park, Rebecca J.; Singh, Ilina; Pike, Alexandra C.; Tan, Jacinta O. A.

    2017-01-01

    Neurosurgical interventions for psychiatric disorders have a long and troubled history (1, 2) but have become much more refined in the last few decades due to the rapid development of neuroimaging and robotic technologies (2). These advances have enabled the design of less invasive techniques, which are more focused, such as deep brain stimulation (DBS) (3). DBS involves electrode insertion into specific neural targets implicated in pathological behavior, which are then repeatedly stimulated at adjustable frequencies. DBS has been used for Parkinson’s disease and movement disorders since the 1960s (4–6) and over the last decade has been applied to treatment-refractory psychiatric disorders, with some evidence of benefit in obsessive–compulsive disorder (OCD), major depressive disorder, and addictions (7). Recent consensus guidelines on best practice in psychiatric neurosurgery (8) stress, however, that DBS for psychiatric disorders remains at an experimental and exploratory stage. The ethics of DBS—in particular for psychiatric conditions—is debated (1, 8–10). Much of this discourse surrounds the philosophical implications of competence, authenticity, personality, or identity change following neurosurgical interventions, but there is a paucity of applied guidance on neuroethical best practice in psychiatric DBS, and health-care professionals have expressed that they require more (11). This paper aims to redress this balance by providing a practical, applied neuroethical gold standard framework to guide research ethics committees, researchers, and institutional sponsors. We will describe this as applied to our protocol for a particular research trial of DBS in severe and enduring anorexia nervosa (SE-AN) (https://clinicaltrials.gov/ct2/show/NCT01924598, unique identifier NCT01924598), but believe it may have wider application to DBS in other psychiatric disorders. PMID:28373849

  4. Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS

    PubMed Central

    Foltynie, Tom; Zrinzo, Ludvic; Hyam, Jonathan A.; Limousin, Patricia

    2017-01-01

    Objective. Reduced verbal fluency is a strikingly uniform finding following deep brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive mechanism underlying this reduction remains unclear, but theories have suggested reduced motivation, linguistic skill, and/or executive function. It is of note, however, that previous reports have failed to consider the potential role of any changes in speed of processing. Thus, the aim of this study was to examine verbal fluency changes with a particular focus on the role of cognitive speed. Method. In this study, 28 patients with PD completed measures of verbal fluency, motivation, language, executive functioning, and speed of processing, before and after DBS. Results. As expected, there was a marked decline in verbal fluency but also in a timed test of executive functions and two measures of speed of processing. Verbal fluency decline was associated with markers of linguistic and executive functioning, but not after speed of processing was statistically controlled for. In contrast, greater decline in verbal fluency was associated with higher levels of apathy at baseline, which was not associated with changes in cognitive speed. Discussion. Reduced generativity and processing speed may account for the marked reduction in verbal fluency commonly observed following DBS.

  5. Post-mortem Findings in Huntington’s Deep Brain Stimulation: A Moving Target Due to Atrophy

    PubMed Central

    Vedam-Mai, Vinata; Martinez-Ramirez, Daniel; Hilliard, Justin D.; Carbunaru, Samuel; Yachnis, Anthony T.; Bloom, Joshua; Keeling, Peyton; Awe, Lisa; Foote, Kelly D.; Okun, Michael S.

    2016-01-01

    Background Deep brain stimulation (DBS) has been shown to be effective for Parkinson’s disease, essential tremor, and primary dystonia. However, mixed results have been reported in Huntington’s disease (HD). Case Report A single case of HD DBS was identified from the University of Florida DBS Brain Tissue Network. The clinical presentation, evolution, surgical planning, DBS parameters, clinical outcomes, and brain pathological changes are summarized. Discussion This case of HD DBS revealed that chorea may improve and be sustained. Minimal histopathological changes were noted around the DBS leads. Severe atrophy due to HD likely changed the DBS lead position relative to the internal capsule. PMID:27127722

  6. Electrode alignment of transverse tripoles using a percutaneous triple-lead approach in spinal cord stimulation

    NASA Astrophysics Data System (ADS)

    Sankarasubramanian, V.; Buitenweg, J. R.; Holsheimer, J.; Veltink, P.

    2011-02-01

    The aim of this modeling study is to determine the influence of electrode alignment of transverse tripoles on the paresthesia coverage of the pain area in spinal cord stimulation, using a percutaneous triple-lead approach. Transverse tripoles, comprising a central cathode and two lateral anodes, were modeled on the low-thoracic vertebral region (T10-T12) using percutaneous triple-lead configurations, with the center lead on the spinal cord midline. The triple leads were oriented both aligned and staggered. In the staggered configuration, the anodes were offset either caudally (caudally staggered) or rostrally (rostrally staggered) with respect to the midline cathode. The transverse tripolar field steering with the aligned and staggered configurations enabled the estimation of dorsal column fiber thresholds (IDC) and dorsal root fiber thresholds (IDR) at various anodal current ratios. IDC and IDR were considerably higher for the aligned transverse tripoles as compared to the staggered transverse tripoles. The aligned transverse tripoles facilitated deeper penetration into the medial dorsal columns (DCs). The staggered transverse tripoles always enabled broad and bilateral DC activation, at the expense of mediolateral steerability. The largest DC recruited area was obtained with the rostrally staggered transverse tripole. Transverse tripolar geometries, using percutaneous leads, allow for selective targeting of either medial or lateral DC fibers, if and only if the transverse tripole is aligned. Steering of anodal currents between the lateral leads of the staggered transverse tripoles cannot target medially confined populations of DC fibers in the spinal cord. An aligned transverse tripolar configuration is strongly recommended, because of its ability to provide more post-operative flexibility than other configurations.

  7. Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation

    NASA Astrophysics Data System (ADS)

    Yazdan-Shahmorad, A.; Lehmkuhle, M. J.; Gage, G. J.; Marzullo, T. C.; Parikh, H.; Miriani, R. M.; Kipke, D. R.

    2011-08-01

    While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation

  8. Generation and evaluation of an ultra-high-field atlas with applications in DBS planning

    NASA Astrophysics Data System (ADS)

    Wang, Brian T.; Poirier, Stefan; Guo, Ting; Parrent, Andrew G.; Peters, Terry M.; Khan, Ali R.

    2016-03-01

    Purpose Deep brain stimulation (DBS) is a common treatment for Parkinson's disease (PD) and involves the use of brain atlases or intrinsic landmarks to estimate the location of target deep brain structures, such as the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi). However, these structures can be difficult to localize with conventional clinical magnetic resonance imaging (MRI), and thus targeting can be prone to error. Ultra-high-field imaging at 7T has the ability to clearly resolve these structures and thus atlases built with these data have the potential to improve targeting accuracy. Methods T1 and T2-weighted images of 12 healthy control subjects were acquired using a 7T MR scanner. These images were then used with groupwise registration to generate an unbiased average template with T1w and T2w contrast. Deep brain structures were manually labelled in each subject by two raters and rater reliability was assessed. We compared the use of this unbiased atlas with two other methods of atlas-based segmentation (single-template and multi-template) for subthalamic nucleus (STN) segmentation on 7T MRI data. We also applied this atlas to clinical DBS data acquired at 1.5T to evaluate its efficacy for DBS target localization as compared to using a standard atlas. Results The unbiased templates provide superb detail of subcortical structures. Through one-way ANOVA tests, the unbiased template is significantly (p <0.05) more accurate than a single-template in atlas-based segmentation and DBS target localization tasks. Conclusion The generated unbiased averaged templates provide better visualization of deep brain nuclei and an increase in accuracy over single-template and lower field strength atlases.

  9. Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats

    PubMed Central

    Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G.

    2012-01-01

    Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect. PMID:22692938

  10. Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem.

    PubMed

    Holiga, Štefan; Mueller, Karsten; Möller, Harald E; Urgošík, Dušan; Růžička, Evžen; Schroeter, Matthias L; Jech, Robert

    2015-01-01

    During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a "microlesion effect" (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

  11. Comparison of Proximally Versus Distally Placed Spatially Distributed Sequential Stimulation Electrodes in a Dynamic Knee Extension Task

    PubMed Central

    Laubacher, Marco; Aksöz, Efe A.; Binder-Macleod, Stuart; Hunt, Kenneth J.

    2016-01-01

    Spatially distributed sequential stimulation (SDSS) has demonstrated substantial power output and fatigue benefits compared to single electrode stimulation (SES) in the application of functional electrical stimulation (FES). This asymmetric electrode setup brings new possibilities but also new questions since precise placement of the electrodes is one critical factor for good muscle activation. The aim of this study was to compare the power output, fatigue and activation properties of proximally versus distally placed SDSS electrodes in an isokinetic knee extension task simulating knee movement during recumbent cycling. M. vastus lateralis and medialis of seven able-bodied subjects were stimulated with rectangular bi-phasic pulses of constant amplitude of 40 mA and at an SDSS frequency of 35 Hz for 6 min on both legs with both setups (i.e. n=14). Torque was measured during knee-extension movement by a dynamometer at an angular velocity of 110 deg/s. Mean power, peak power and activation time were calculated and compared for the initial and final stimulation phases, together with an overall fatigue index. Power output values (Pmean, Ppeak) were scaled to a standardised reference input pulse width of 100 μs (Pmean,s, Ppeak,s). The initial evaluation phase showed no significant differences between the two setups for all outcome measures. Ppeak and Ppeak,s were both significantly higher in the final phase for the distal setup (25.4 ± 8.1 W vs. 28.2 ± 6.2 W, p=0.0062 and 34.8 ± 9.5 W vs. 38.9 ± 6.7 W, p=0.021, respectively). With distal SDSS, there was modest evidence of higher Pmean and Pmean,s (p=0.071, p=0.14, respectively) but of longer activation time (p=0.096). The rate of fatigue was similar for both setups. For practical FES applications, distal placement of the SDSS electrodes is preferable. PMID:27478563

  12. Validation of a Portable Low-power Deep Brain Stimulation Device through Anxiolytic Effects in a Laboratory Rat Model.

    PubMed

    Kouzani, Abbas Z; Kale, Rajas P; Zarate-Garza, Pablo Patricio; Berk, Michael; Walder, Ken; Tye, Susannah J

    2016-11-15

    Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, portability, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength 200 μA, width 90 μs, and frequency 130 Hz for 22.75 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.

  13. Improvement of Electrical Stimulation Protocol for Simultaneous Measurement of Extracellular Potential with On-Chip Multi-Electrode Array System

    NASA Astrophysics Data System (ADS)

    Kaneko, Tomoyuki; Nomura, Fumimasa; Hattori, Akihiro; Yasuda, Kenji

    2012-06-01

    Cardiotoxicity testing with a multi-electrode array (MEA) system requires the stable beating of cardiomyocytes for the measurement of the field potential duration (FPD), because different spontaneous beating rates cause different responses of FPD prolongation induced by drugs, and the beating rate change effected by drugs complicates the FPD prolongation assessment. We have developed an on-chip MEA system with electrical stimulation for the measurement of the FPD during the stable beating of human embryonic stem (ES) cell-derived cardiomyocyte clusters. Using a conventional bipolar stimulation protocol, we observed such large artifacts in electrical stimulation that we could not estimate the FPD quantitatively. Therefore, we improved the stimulation protocol by using sequential rectangular pulses in which the positive and negative stimulation voltages and number of pulses could be changed flexibly. The balanced voltages and number of pulses for sequential rectangular pulses enabled the recording of small negative artifacts only, which hardly affected the FPD measurement of human-ES-cell-derived cardiomyocyte clusters. These conditions of electrical stimulation are expected to find applications for the control of constant beating for cardiotoxicity testing.

  14. Influence of electrode configuration on the electric field distribution during transcutaneous spinal direct current stimulation of the cervical spine.

    PubMed

    Fernandes, Sofia R; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede A; Miranda, Pedro C; Fernandes, Sofia R; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede A; Miranda, Pedro C; Fernandes, Sofia R; Miranda, Pedro C; Wenger, Cornelia; Salvador, Ricardo; de Carvalho, Mamede A

    2016-08-01

    Transcutaneous spinal direct current stimulation (tsDCS) is a recent technique with promising neuromodulatory effects on spinal neuronal circuitry. The main objective of the present study was to perform a finite element analysis of the electric field distribution in tsDCS in the cervical spine region, with varying electrode configurations and geometry. A computational model of a human trunk was generated with nine tissue meshes. Three electrode configurations were tested: A) rectangular saline-soaked sponge target and return electrodes placed over C3 and T3 spinous processes, respectively; B1) circular saline-soaked sponge target and return electrodes placed over C7 spinous process and right deltoid muscle, respectively; B2) same configuration as B1, considering circular shaped electrodes with sponge and rubber layers and a small circular connector on the top surface. The electric field distribution for cervical tsDCS predicted higher magnitude in configurations B1 and B2, reaching a maximum of 0.71 V/m in the spinal white matter and 0.43 V/m in the spinal grey matter, with values above 0.15 V/m in the region of the spinal circuits related with upper limb innervation. In configuration A, the values were found to be <; 0.15 V/m through the entire spinal cord. Electric fields with magnitude above 0.15 V/m are thought to be effective in neuromodulation of the human cerebral cortex, so the configurations B1 and B2 could be an optimal choice for cervical tsDCS protocols. Computational studies using realistic models may be a powerful tool to predict physical effects of tsDCS on the cervical spinal cord and to optimize electrode placement focused on specific neurologic patient needs related with upper limb function.

  15. Atlas of the muscle motor points for the lower limb: implications for electrical stimulation procedures and electrode positioning.

    PubMed

    Botter, Alberto; Oprandi, Gianmosè; Lanfranco, Fabio; Allasia, Stefano; Maffiuletti, Nicola A; Minetto, Marco Alessandro

    2011-10-01

    The aim of the study was to investigate the uniformity of the muscle motor point location for lower limb muscles in healthy subjects. Fifty-three subjects of both genders (age range: 18-50 years) were recruited. The muscle motor points were identified for the following ten muscles of the lower limb (dominant side): vastus medialis, rectus femoris, and vastus lateralis of the quadriceps femoris, biceps femoris, semitendinosus, and semimembranosus of the hamstring muscles, tibialis anterior, peroneus longus, lateral and medial gastrocnemius. The muscle motor point was identified by scanning the skin surface with a stimulation pen electrode and corresponded to the location of the skin area above the muscle in which an electrical pulse evoked a muscle twitch with the least injected current. For each investigated muscle, 0.15 ms square pulses were delivered through the pen electrode at low current amplitude (<10 mA) and frequency (2 Hz). 16 motor points were identified in the 10 investigated muscles of almost all subjects: 3 motor points for the vastus lateralis, 2 motor points for rectus femoris, vastus medialis, biceps femoris, and tibialis anterior, 1 motor point for the remaining muscles. An important inter-individual variability was observed for the position of the following 4 out of 16 motor points: vastus lateralis (proximal), biceps femoris (short head), semimembranosus, and medial gastrocnemius. Possible implications for electrical stimulation procedures and electrode positioning different from those commonly applied for thigh and leg muscles are discussed.

  16. Effect of electrode impedance on spread of excitation and pitch perception using electrically coupled “dual-electrode” stimulation

    PubMed Central

    Hughes, Michelle L.; Baudhuin, Jacquelyn L.; Goehring, Jenny L.

    2014-01-01

    Objective In newer-generation Cochlear Ltd. cochlear implants, two adjacent electrodes can be electrically coupled to produce a single contact or “dual electrode” (DE). The goal of the present study was to evaluate whether relatively large impedance differences (>3.0 kOhms) between coupled electrodes affect the excitation pattern and pitch percepts produced by the DE. Design Fifteen electrode pairs in six recipients were tested. Neural spread-of-excitation (SOE) patterns and pitch perception were measured for adjacent physical electrodes (PEs) and the resulting DE to determine if the lower-impedance PE in the pair dominates the DE response pattern. Results were compared to a “normative sample” (impedance differences <3.0 kOhms) from two earlier studies. Results In general, SOE patterns for DEs more closely approximated those of the lower-impedance PE in each pair. The DE was more easily distinguished in pitch from the higher-impedance PE than the lower-impedance PE. The ECAP and perceptual results generally differed from those of the normative group. Conclusions Impedance differences between adjacent PEs should be considered if DE stimulation is implemented in future research studies or clinical coding strategies. PMID:25250960

  17. Supporting clinical decision making during deep brain stimulation surgery by means of a stochastic dynamical model

    NASA Astrophysics Data System (ADS)

    Karamintziou, Sofia D.; Tsirogiannis, George L.; Stathis, Pantelis G.; Tagaris, George A.; Boviatsis, Efstathios J.; Sakas, Damianos E.; Nikita, Konstantina S.

    2014-10-01

    Objective. During deep brain stimulation (DBS) surgery for the treatment of advanced Parkinson's disease (PD), microelectrode recording (MER) in conjunction with functional stimulation techniques are commonly applied for accurate electrode implantation. However, the development of automatic methods for clinical decision making has to date been characterized by the absence of a robust single-biomarker approach. Moreover, it has only been restricted to the framework of MER without encompassing intraoperative macrostimulation. Here, we propose an integrated series of novel single-biomarker approaches applicable to the entire electrophysiological procedure by means of a stochastic dynamical model. Approach. The methods are applied to MER data pertinent to ten DBS procedures. Considering the presence of measurement noise, we initially employ a multivariate phase synchronization index for automatic delineation of the functional boundaries of the subthalamic nucleus (STN) and determination of the acceptable MER trajectories. By introducing the index into a nonlinear stochastic model, appropriately fitted to pre-selected MERs, we simulate the neuronal response to periodic stimuli (130 Hz), and examine the Lyapunov exponent as an indirect indicator of the clinical effectiveness yielded by stimulation at the corresponding sites. Main results. Compared with the gold-standard dataset of annotations made intraoperatively by clinical experts, the STN detection methodology demonstrates a false negative rate of 4.8% and a false positive rate of 0%, across all trajectories. Site eligibility for implantation of the DBS electrode, as implicitly determined through the Lyapunov exponent of the proposed stochastic model, displays a sensitivity of 71.43%. Significance. The suggested comprehensive method exhibits remarkable performance in automatically determining both the acceptable MER trajectories and the optimal stimulation sites, thereby having the potential to accelerate precise

  18. Electrical stimulation of non-classical photon emission from diamond color centers by means of sub-superficial graphitic electrodes

    PubMed Central

    Forneris, Jacopo; Traina, Paolo; Monticone, Daniele Gatto; Amato, Giampiero; Boarino, Luca; Brida, Giorgio; Degiovanni, Ivo P.; Enrico, Emanuele; Moreva, Ekaterina; Grilj, Veljko; Skukan, Natko; Jakšić, Milko; Genovese, Marco; Olivero, Paolo

    2015-01-01

    Focused MeV ion beams with micrometric resolution are suitable tools for the direct writing of conductive graphitic channels buried in an insulating diamond bulk, as already demonstrated for different device applications. In this work we apply this fabrication method to the electrical excitation of color centers in diamond, demonstrating the potential of electrical stimulation in diamond-based single-photon sources. Differently from optically-stimulated light emission from color centers in diamond, electroluminescence (EL) requires a high current flowing in the diamond subgap states between the electrodes. With this purpose, buried graphitic electrode pairs, 10 μm spaced, were fabricated in the bulk of a single-crystal diamond sample using a 6 MeV C microbeam. The electrical characterization of the structure showed a significant current injection above an effective voltage threshold of 150 V, which enabled the stimulation of a stable EL emission. The EL imaging allowed to identify the electroluminescent regions and the residual vacancy distribution associated with the fabrication technique. Measurements evidenced isolated electroluminescent spots where non-classical light emission in the 560–700 nm spectral range was observed. The spectral and auto-correlation features of the EL emission were investigated to qualify the non-classical properties of the color centers. PMID:26510889

  19. Electrical stimulation of non-classical photon emission from diamond color centers by means of sub-superficial graphitic electrodes

    NASA Astrophysics Data System (ADS)

    Forneris, Jacopo; Traina, Paolo; Monticone, Daniele Gatto; Amato, Giampiero; Boarino, Luca; Brida, Giorgio; Degiovanni, Ivo P.; Enrico, Emanuele; Moreva, Ekaterina; Grilj, Veljko; Skukan, Natko; Jakšić, Milko; Genovese, Marco; Olivero, Paolo

    2015-10-01

    Focused MeV ion beams with micrometric resolution are suitable tools for the direct writing of conductive graphitic channels buried in an insulating diamond bulk, as already demonstrated for different device applications. In this work we apply this fabrication method to the electrical excitation of color centers in diamond, demonstrating the potential of electrical stimulation in diamond-based single-photon sources. Differently from optically-stimulated light emission from color centers in diamond, electroluminescence (EL) requires a high current flowing in the diamond subgap states between the electrodes. With this purpose, buried graphitic electrode pairs, 10 μm spaced, were fabricated in the bulk of a single-crystal diamond sample using a 6 MeV C microbeam. The electrical characterization of the structure showed a significant current injection above an effective voltage threshold of 150 V, which enabled the stimulation of a stable EL emission. The EL imaging allowed to identify the electroluminescent regions and the residual vacancy distribution associated with the fabrication technique. Measurements evidenced isolated electroluminescent spots where non-classical light emission in the 560-700 nm spectral range was observed. The spectral and auto-correlation features of the EL emission were investigated to qualify the non-classical properties of the color centers.

  20. Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees

    NASA Astrophysics Data System (ADS)

    Tan, Daniel W.; Schiefer, Matthew A.; Keith, Michael W.; Anderson, J. Robert; Tyler, Dustin J.

    2015-04-01

    Objective. Stability and selectivity are important when restoring long-term, functional sensory feedback in individuals with limb-loss. Our objective is to demonstrate a chronic, clinical neural stimulation system for providing selective sensory response in two upper-limb amputees. Approach. Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of the upper-limb. Main results. Nerve stimulation produced a selective sensory response on 19 of 20 contacts and 16 of 16 contacts in subjects 1 and 2, respectively. Stimulation elicited multiple, distinct percept areas on the phantom and residual limb. Consistent threshold, impedance, and percept areas have demonstrated that the neural interface is stable for the duration of this on-going, chronic study. Significance. We have achieved selective nerve response from multi-contact cuff electrodes by demonstrating characteristic percept areas and thresholds for each contact. Selective sensory response remains consistent in two upper-limb amputees for 1 and 2 years, the longest multi-contact sensory feedback system to date. Our approach demonstrates selectivity and stability can be achieved through an extraneural interface, which can provide sensory feedback to amputees.

  1. Ultra-high magnetic resonance imaging (MRI): a potential examination for deep brain stimulation devices and the limitation study concerning MRI-related heating injury.

    PubMed

    Chen, Ying-Chuan; Li, Jun-Ju; Zhu, Guan-Yu; Shi, Lin; Yang, An-Chao; Jiang, Yin; Zhang, Xin; Zhang, Jian-Guo

    2017-03-01

    Nowadays, the patients with deep brain stimulation (DBS) devices are restricted to undertake 1.5T magnetic resonance imaging (MRI) according to the guideline. Nevertheless, we conducted an experiment to test pathological change near the leads in different field-strength MRI. Twenty-four male New Zealand rabbits were assigned to Group 1 (G1, n = 6, 7.0T, DBS), Group 2 (G2, n = 6, 3.0T, DBS), Group 3 (G3, n = 6, 1.5T, DBS), and Group 4 (G4, n = 6, 1.5T, paracentesis). DBS leads were implanted in G1, G2 and G3, targeting left nucleus ventralis posterior thalami. Paracentesis was performed in G4. 24 h after MRI scan, all animals were killed for examining pathological alternation (at different distance from lead) via transmission electron microscopy. Our results suggest that the severity of tissue injury correlates with the distance to electrode instead of field strength of MRI. Up to now, the reason for the restriction of MRI indicated no significantly different pathological change.

  2. Management of impulse control disorders with deep brain stimulation: A double-edged sword.

    PubMed

    Kasemsuk, Chayut; Oyama, Genko; Hattori, Nobutaka

    2017-03-15

    Deep brain stimulation (DBS) is a surgical option for advanced Parkinson's disease. Although DBS is used to treat motor fluctuation, DBS may affect non-motor symptoms including mood disorders, cognitive dysfunction, and behavior problems. Impulse control disorders (ICDs) are abnormal behaviors with various manifestations such as pathological gambling, hypersexuality, compulsive shopping, and binge eating, which can affect the quality of life in patients with Parkinson's disease. The effect of DBS on ICD is controversial. Reducing medication by DBS may improve ICDs, however, worsening or even developing new ICDs after DBS can occur. We will review the impact of DBS on ICDs and reveal factors associated with a good response to DBS as well as risk factors for developing ICDs after DBS. We also propose a strategy to manage preexisting ICD and prevent postoperative de novo ICDs.

  3. DBS Radio: Deathstar or Dud? Info. Packets No. 24.

    ERIC Educational Resources Information Center

    Pizzi, Skip

    The Federal Communications Commission (FCC) has been progressing over the past 5 years toward the institution of Direct Broadcast Satellite Radio (DBS-R) which would institute a new type of radio service. The FCC refers to the service as Satellite DARS (Digital Audio Radio Service), and it would provide reliable, high-fidelity satellite-delivered…

  4. Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography.

    PubMed

    Markser, A; Maier, Franziska; Lewis, C J; Dembek, T A; Pedrosa, D; Eggers, C; Timmermann, L; Kalbe, E; Fink, G R; Burghaus, Lothar

    2015-10-01

    Some Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) develop new-onset cognitive decline. We examined whether clinical EEG recordings can be used to predict cognitive deterioration in PD patients undergoing STN-DBS. In this retrospective study, we used the Grand Total EEG (GTE)-score (short and total) to evaluate pre- and postoperative EEGs. In PD patients undergoing STN-DBS (N = 30), cognitive functioning was measured using Mini-Mental State Test and DemTect before and after surgery. Severity of motor impairment was assessed using the Unified Parkinson's Disease Rating Scale-III. Patients were classified into patients with or without cognitive decline after STN-DBS surgery. Epidemiological data, pre- and postoperative EEG recordings as well as neuropsychological and neurological data, electrode positions and the third ventricle width were compared. A logistic regression model was used to identify predictors of cognitive decline. Motor deficits significantly improved from pre- to post-surgery, while the mean GTE-scores increased significantly. Six patients developed cognitive deterioration 4-12 months postoperatively. These patients had significantly higher preoperative GTE-scores than patients without cognitive deterioration, although preoperative cognitive functioning was comparable. Electrode positions, brain atrophy and neurological data did not differ between groups. Logistic regression analysis identified the GTE-score as a significant predictor of postoperative cognitive deterioration. Data suggest that the preoperative GTE-score can be used to identify PD patients that are at high risk for developing cognitive deterioration after STN-DBS surgery even though their preoperative cognitive state was normal.

  5. Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes

    PubMed Central

    Maks, Christopher B.; Butson, Christopher R.; Walter, Benjamin L.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2010-01-01

    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 PD patients, 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 pre-operative imaging data; 2) entry of intra-operative microelectrode recording locations from neurophysiologically defined thalamic, subthalamic, and substantia nigra neurons into the context of the imaging data; 3) fitting a 3D brain atlas to the neuroanatomy and neurophysiology of the patient; 4) positioning the DBS electrode in the documented stereotactic location, verified by post-operative 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 5 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. Further, of the 5 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. PMID:18403440

  6. Electron transfer processes occurring on platinum neural stimulating electrodes: a tutorial on the i(V e) profile

    NASA Astrophysics Data System (ADS)

    Kumsa, Doe W.; Bhadra, Narendra; Hudak, Eric M.; Kelley, Shawn C.; Untereker, Darrel F.; Mortimer, J. Thomas

    2016-10-01

    The aim of this tutorial is to encourage members of the neuroprosthesis community to incorporate electron transfer processes into their thinking and provide them with the tools to do so when they design and work with neurostimulating devices. The focus of this article is on platinum because it is the most used electrode metal for devices in commercial use. The i(V e) profile or cyclic voltammogram contains information about electron transfer processes that can occur when the electrode-electrolyte interface, V e, is at a specific potential, and assumed to be near steady-state conditions. For the engineer/designer this means that if the potential is not in the range of a specific electron transfer process, that process cannot occur. An i(V e) profile, recorded at sweep rates greater than 0.1 mVs-1, approximates steady-state conditions. Rapid transient potential excursions, like that seen with neural stimulation pulses, may be too fast for the reaction to occur, however, this means that if the potential is in the range of a specific electron transfer process it may occur and should be considered. The approach described here can be used to describe the thermodynamic electron transfer processes on other candidate electrode metals, e.g. stainless steel, iridium, carbon-based, etc.

  7. Posterior occipitocervical instrumented fusion for dropped head syndrome after deep brain stimulation.

    PubMed

    Pereira, E A C; Wilson-MacDonald, J; Green, A L; Aziz, T Z; Cadoux-Hudson, T A D

    2010-04-01

    We describe dropped head syndrome in a patient with Parkinson's disease receiving subthalamic nucleus deep brain stimulation (DBS). Posterior occipitocervical instrumented fusion after transarticular screw fixation of an odontoid fracture is shown and its rationale explained. Pedunculopontine nucleus DBS as treatment for fall-predominant Parkinson's disease, and globus pallidus interna DBS for dystonia-predominant Parkinson's disease, are discussed.

  8. Influence of heterogeneous and anisotropic tissue conductivity on electric field distribution in deep brain stimulation.

    PubMed

    Aström, Mattias; Lemaire, Jean-Jacques; Wårdell, Karin

    2012-01-01

    The aim was to quantify the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the spatial distribution of the electric field during deep brain stimulation (DBS). Three finite element tissue models were created of one patient treated with DBS. Tissue conductivity was modelled as (I) homogeneous isotropic, (II) heterogeneous isotropic based on MRI, and (III) heterogeneous anisotropic based on diffusion tensor MRI. Modelled DBS electrodes were positioned in the subthalamic area, the pallidum, and the internal capsule in each tissue model. Electric fields generated during DBS were simulated for each model and target-combination and visualized with isolevels at 0.20 (inner), and 0.05 V mm(-1) (outer). Statistical and vector analysis was used for evaluation of the distribution of the electric field. Heterogeneous isotropic tissue altered the spatial distribution of the electric field by up to 4% at inner, and up to 10% at outer isolevel. Heterogeneous anisotropic tissue influenced the distribution of the electric field by up to 18 and 15% at each isolevel, respectively. The influence of heterogeneous and anisotropic tissue on the electric field may be clinically relevant in anatomic regions that are functionally subdivided and surrounded by multiple fibres of passage.

  9. Body weight gain rate in patients with Parkinson's disease and deep brain stimulation.

    PubMed

    Barichella, Michela; Marczewska, Agnieszka M; Mariani, Claudio; Landi, Andrea; Vairo, Antonella; Pezzoli, Gianni

    2003-11-01

    We evaluated body weight changes in patients with Parkinson's disease (PD) after electrode implantation for deep brain stimulation (DBS) in the subthalamic nucleus (STN) in relation to clinical improvement. Thirty PD patients who received STN DBS were included (22 men, 8 women; mean age, 60.0 +/- 7.1 years; mean PD duration, 13.5 +/- 3.7 years; mean body mass index [BMI], 21.6 +/- 3.0 kg/m2). Body weight, physical activity, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were noted before and 3 and 12 months after the procedure. Significant weight gain occurred in 29 patients; the mean increase was 14.8 +/- 9.8% of initial body weight in 1 year. Of the patients, 46.5% reported weight gain in the first 3 months, 21.4% gradual weight gain in the first 6 months, and 32.1% a slow increase for 1 year. Mean BMI increased up to 24.7 +/- 3.7 kg/m2. After 1 year, mean UPDRS motor score improved significantly in off and in on; and therapy complications improved by 91.0 +/- 17.0%. BMI changes at 3 and 12 months were significantly correlated to dyskinesia score changes, and levodopa dosage was not. In PD, STN DBS produces not only symptom control, but also weight gain. DBS candidates should be given nutritional counseling before the intervention to prevent rapid and/or excessive weight gain.

  10. Evaluation of local electric fields generated by transcranial direct current stimulation with an extracephalic reference electrode based on realistic 3D body modeling

    NASA Astrophysics Data System (ADS)

    Im, Chang-Hwan; Park, Ji-Hye; Shim, Miseon; Chang, Won Hyuk; Kim, Yun-Hee

    2012-04-01

    In this study, local electric field distributions generated by transcranial direct current stimulation (tDCS) with an extracephalic reference electrode were evaluated to address extracephalic tDCS safety issues. To this aim, we generated a numerical model of an adult male human upper body and applied the 3D finite element method to electric current conduction analysis. In our simulations, the active electrode was placed over the left primary motor cortex (M1) and the reference electrode was placed at six different locations: over the right temporal lobe, on the right supraorbital region, on the right deltoid, on the left deltoid, under the chin, and on the right buccinator muscle. The maximum current density and electric field intensity values in the brainstem generated by the extracephalic reference electrodes were comparable to, or even less than, those generated by the cephalic reference electrodes. These results suggest that extracephalic reference electrodes do not lead to unwanted modulation of the brainstem cardio-respiratory and autonomic centers, as indicated by recent experimental studies. The volume energy density was concentrated at the neck area by the use of deltoid reference electrodes, but was still smaller than that around the active electrode locations. In addition, the distributions of elicited cortical electric fields demonstrated that the use of extracephalic reference electrodes might allow for the robust prediction of cortical modulations with little dependence on the reference electrode locations.

  11. Evaluation of local electric fields generated by transcranial direct current stimulation with an extracephalic reference electrode based on realistic 3D body modeling.

    PubMed

    Im, Chang-Hwan; Park, Ji-Hye; Shim, Miseon; Chang, Won Hyuk; Kim, Yun-Hee

    2012-04-21

    In this study, local electric field distributions generated by transcranial direct current stimulation (tDCS) with an extracephalic reference electrode were evaluated to address extracephalic tDCS safety issues. To this aim, we generated a numerical model of an adult male human upper body and applied the 3D finite element method to electric current conduction analysis. In our simulations, the active electrode was placed over the left primary motor cortex (M1) and the reference electrode was placed at six different locations: over the right temporal lobe, on the right supraorbital region, on the right deltoid, on the left deltoid, under the chin, and on the right buccinator muscle. The maximum current density and electric field intensity values in the brainstem generated by the extracephalic reference electrodes were comparable to, or even less than, those generated by the cephalic reference electrodes. These results suggest that extracephalic reference electrodes do not lead to unwanted modulation of the brainstem cardio-respiratory and autonomic centers, as indicated by recent experimental studies. The volume energy density was concentrated at the neck area by the use of deltoid reference electrodes, but was still smaller than that around the active electrode locations. In addition, the distributions of elicited cortical electric fields demonstrated that the use of extracephalic reference electrodes might allow for the robust prediction of cortical modulations with little dependence on the reference electrode locations.

  12. Deep brain stimulation for obesity: past, present, and future targets.

    PubMed

    Dupré, Derrick A; Tomycz, Nestor; Oh, Michael Y; Whiting, Donald

    2015-06-01

    The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation--caloric intake and energy expenditure.

  13. Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

    The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation

  14. Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications

    PubMed Central

    Xiao, YiZi; Zitella, Laura M.; Duchin, Yuval; Teplitzky, Benjamin A.; Kastl, Daniel; Adriany, Gregor; Yacoub, Essa; Harel, Noam; Johnson, Matthew D.

    2016-01-01

    Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS. PMID:27375422

  15. Endovascular Electrodes for Electrical Stimulation of Blood Vessels for Vasoconstriction – a Finite Element Simulation Study

    NASA Astrophysics Data System (ADS)

    Kezurer, Noa; Farah, Nairouz; Mandel, Yossi

    2016-08-01

    Hemorrhagic shock accounts for 30–40 percent of trauma mortality, as bleeding may sometimes be hard to control. Application of short electrical pulses on blood vessels was recently shown to elicit robust vasoconstriction and reduction of blood loss following vascular injury. In this study we present a novel approach for vasoconstriction based on endovascular application of electrical pulses for situations where access to the vessel is limited. In addition to ease of access, we hypothesize that this novel approach will result in a localized and efficient vasoconstriction. Using computer modeling (COMSOL Multiphysics, Electric Currents Module), we studied the effect of endovascular pulsed electrical treatment on abdominal aorta of pigs, and compared the efficiency of different electrodes configurations on the electric field amplitude, homogeneity and locality when applied on a blood vessel wall. Results reveal that the optimal configuration is the endovascular approach where four electrodes are used, spaced 13 mm apart. Furthermore, computer based temperature investigations (bio-heat model, COMSOL Multiphysics) show that the maximum expected temperature rise is of 1.2 degrees; highlighting the safety of the four endovascular electrodes configuration. These results can aid in planning the application of endovascular pulsed electrical treatment as an efficient and safe vasoconstriction approach.

  16. Endovascular Electrodes for Electrical Stimulation of Blood Vessels for Vasoconstriction - a Finite Element Simulation Study.

    PubMed

    Kezurer, Noa; Farah, Nairouz; Mandel, Yossi

    2016-08-18

    Hemorrhagic shock accounts for 30-40 percent of trauma mortality, as bleeding may sometimes be hard to control. Application of short electrical pulses on blood vessels was recently shown to elicit robust vasoconstriction and reduction of blood loss following vascular injury. In this study we present a novel approach for vasoconstriction based on endovascular application of electrical pulses for situations where access to the vessel is limited. In addition to ease of access, we hypothesize that this novel approach will result in a localized and efficient vasoconstriction. Using computer modeling (COMSOL Multiphysics, Electric Currents Module), we studied the effect of endovascular pulsed electrical treatment on abdominal aorta of pigs, and compared the efficiency of different electrodes configurations on the electric field amplitude, homogeneity and locality when applied on a blood vessel wall. Results reveal that the optimal configuration is the endovascular approach where four electrodes are used, spaced 13 mm apart. Furthermore, computer based temperature investigations (bio-heat model, COMSOL Multiphysics) show that the maximum expected temperature rise is of 1.2 degrees; highlighting the safety of the four endovascular electrodes configuration. These results can aid in planning the application of endovascular pulsed electrical treatment as an efficient and safe vasoconstriction approach.

  17. Endovascular Electrodes for Electrical Stimulation of Blood Vessels for Vasoconstriction – a Finite Element Simulation Study

    PubMed Central

    Kezurer, Noa; Farah, Nairouz; Mandel, Yossi

    2016-01-01

    Hemorrhagic shock accounts for 30–40 percent of trauma mortality, as bleeding may sometimes be hard to control. Application of short electrical pulses on blood vessels was recently shown to elicit robust vasoconstriction and reduction of blood loss following vascular injury. In this study we present a novel approach for vasoconstriction based on endovascular application of electrical pulses for situations where access to the vessel is limited. In addition to ease of access, we hypothesize that this novel approach will result in a localized and efficient vasoconstriction. Using computer modeling (COMSOL Multiphysics, Electric Currents Module), we studied the effect of endovascular pulsed electrical treatment on abdominal aorta of pigs, and compared the efficiency of different electrodes configurations on the electric field amplitude, homogeneity and locality when applied on a blood vessel wall. Results reveal that the optimal configuration is the endovascular approach where four electrodes are used, spaced 13 mm apart. Furthermore, computer based temperature investigations (bio-heat model, COMSOL Multiphysics) show that the maximum expected temperature rise is of 1.2 degrees; highlighting the safety of the four endovascular electrodes configuration. These results can aid in planning the application of endovascular pulsed electrical treatment as an efficient and safe vasoconstriction approach. PMID:27534438

  18. Functional anatomy of subthalamic nucleus stimulation in Parkinson disease

    PubMed Central

    Eisenstein, Sarah A.; Koller, Jonathan M.; Black, Kathleen D.; Campbell, Meghan C.; Lugar, Heather M.; Ushe, Mwiza; Tabbal, Samer D.; Karimi, Morvarid; Hershey, Tamara; Perlmutter, Joel S.; Black, Kevin J.

    2014-01-01

    Objective We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3D brain region and to assign statistical significance after stringent Type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS. Method Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t-tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site. Results Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory). Interpretation Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, since movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive and limbic information in STN. PMID:24953991

  19. [Deep brain stimulation in psychiatry: ethical aspects].

    PubMed

    Müller, Ulf J; Bogerts, Bernhard; Voges, Jürgen; Galazky, Imke; Kohl, Sina; Heinze, Hans-Jochen; Kuhn, Jens; Steiner, Johann

    2014-07-01

    Deep brain stimulation (DBS) has been shown to be an efficacious treatment for many neurological conditions and has thus been expanded to psychiatric diseases as well. Following an introduction on the history of DBS in psychiatry, this review summarizes commonly raised ethical concerns and questions on clinical trial design, selection of patients, informed consent and concerns about the possible impact of DBS on an individual's personality. Finally, it highlights the fact that critique on DBS in psychiatry is probably not selectively based on scientific concerns about potential risks; instead, the neurobiological origin of specific psychiatric disorders has been questioned.

  20. The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson's disease.

    PubMed

    Goelz, Lisa C; David, Fabian J; Sweeney, John A; Vaillancourt, David E; Poizner, Howard; Metman, Leonard Verhagen; Corcos, Daniel M

    2017-02-01

    Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

  1. Review article: anesthetic management of patients undergoing deep brain stimulator insertion.

    PubMed

    Venkatraghavan, Lashmi; Luciano, Michelle; Manninen, Pirjo

    2010-04-01

    Deep brain stimulation is used for the treatment of patients with neurologic disorders who have an alteration of function, such as movement disorders and other chronic illnesses. The insertion of the deep brain stimulator (DBS) is a minimally invasive procedure that includes the placement of electrodes into deep brain structures for microelectrode recordings and intraoperative clinical testing and connection of the DBS to an implanted pacemaker. The anesthetic technique varies depending on the traditions and requirements of each institution performing these procedures and has included monitored anesthesia with local anesthesia, conscious sedation, and general anesthesia. The challenges and demands for the anesthesiologist in the care of these patients relate to the specific concerns of the patients with functional neurologic disorders, the effects of anesthetic drugs on microelectrode recordings, and the requirements of the surgical procedure, which often include an awake and cooperative patient. The purpose of this review is to familiarize anesthesiologists with deep brain stimulation by discussing the mechanism, the effects of anesthetic drugs, and the surgical procedure of DBS insertion, and the perioperative assessment, preparation, intraoperative anesthetic management, and complications in patients with functional neurologic disorders.

  2. DBS systems - Perspectives from a profit seeking company

    NASA Astrophysics Data System (ADS)

    Martin, E. R.

    1984-10-01

    The relationships between various factors necessary for building a successful DBS system are discussed. The system will comprise one satellite with multiple channels for each centerminous U.S. time zone. Operations in the Eastern time zone are scheduled to commence in 1986. Constraints on the establishment of the DBS system include minimizing the star-up costs, particularly for the home antennas and their installation, and maximizing the broadcast power of the satellites at acceptable costs. The latter determines the number of subscribers to the service. Tradeoffs in the start-up system design were constrained by concerns of shortand long-term return strategies and the required level of broadcast quality. It is noted that reception sensitivity may increase by the 1986 start-up time, which could effectively double the potential coverage for a given satellite configuration.

  3. Rapid battery depletion and loss of therapy due to a short circuit in bipolar DBS for essential tremor.

    PubMed

    Allert, Niels; Barbe, Michael Thomas; Timmermann, Lars; Coenen, Volker Arnd

    2017-01-27

    Technical dysfunctions have been reported reducing efficacy of deep brain stimulation (DBS). Here, we report on an essential-tremor patient in whom a short circuit in bipolar DBS resulted not only in unilateral loss of therapy but also in high current flow and thereby rapid decline of the impulse-generator battery voltage from 2.83 V a week before the event to 2.54 V, indicating the need for an impulse-generator replacement. Immediate re-programming restored therapeutic efficacy. Moreover, the reduction in current flow allowed the battery voltage to recover without immediate surgical intervention to 2.81 V a week later.

  4. Changes in the electrical properties of the electrode-skin-underlying tissue composite during a week-long programme of neuromuscular electrical stimulation.

    PubMed

    Bîrlea, S I; Breen, P P; Corley, G J; Bîrlea, N M; Quondamatteo, F; ÓLaighin, G

    2014-02-01

    Particular neuromuscular electrical stimulation (NMES) applications require the use of the same electrodes over a long duration (>1 day) without having access to them. Under such circumstance the quality of the electrode-skin contact cannot be assessed. We used the NMES signal itself to assess the quality of the electrode-skin contact and the electrical properties of the underlying tissues over a week. A 14% decrease in the skin's stratum corneum resistance (from 20 to 17 kΩ) and a 15% decrease in the resistance of the electrodes and underlying tissues (from 550 to 460 Ω) were observed in the 14 healthy subjects investigated. A follow-on investigation of the effect of exercise-induced sweating on the electrical properties of the electrode-skin-underlying tissue composite during NMES indicated a correlation between the decrease in the resistance values observed over the course of the week and the accumulation of sweat at the electrode-skin interface. The value of the capacitance representing the dielectric properties of the skin's stratum corneum increased after exercise-induced sweating but did not change significantly over the course of the week. We conclude that valuable information about the electrode-skin-underlying tissue composite can be gathered using the NMES signal itself, and suggest that this is a practical, safe and relatively simple method for monitoring these electrical properties during long-term stimulation.

  5. Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression

    PubMed Central

    Malone, Donald A.; Dougherty, Darin D.; Rezai, Ali R.; Carpenter, Linda L.; Friehs, Gerhard M.; Eskandar, Emad N.; Rauch, Scott L.; Rasmussen, Steven A.; Machado, Andre G.; Kubu, Cynthia S.; Tyrka, Audrey R.; Price, Lawrence H.; Stypulkowski, Paul H.; Giftakis, Jonathon E.; Rise, Mark T.; Malloy, Paul F.; Salloway, Stephen P.; Greenberg, Benjamin D.

    2012-01-01

    Background We investigated the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) for treatment refractory depression. Methods Fifteen patients with chronic, severe, highly refractory depression received open-label DBS at three collaborating clinical sites. Electrodes were implanted bilaterally in the VC/VS region. Stimulation was titrated to therapeutic benefit and the absence of adverse effects. All patients received continuous stimulation and were followed for a minimum of 6 months to longer than 4 years. Outcome measures included the Hamilton Depression Rating Scale—24 item (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Global Assessment of Function Scale (GAF). Results Significant improvements in depressive symptoms were observed during DBS treatment. Mean HDRS scores declined from 33.1 at baseline to 17.5 at 6 months and 14.3 at last follow-up. Similar improvements were seen with the MADRS (34.8, 17.9, and 15.7, respectively) and the GAF (43.4, 55.5, and 61.8, respectively). Responder rates with the HDRS were 40% at 6 months and 53.3% at last follow-up (MADRS: 46.7% and 53.3%, respectively). Remission rates were 20% at 6 months and 40% at last follow-up with the HDRS (MADRS: 26.6% and 33.3%, respectively). The DBS was well-tolerated in this group. Conclusions Deep brain stimulation of the VC/VS offers promise for the treatment of refractory major depression. PMID:18842257

  6. Stimulation from Cochlear Implant Electrodes Assists with Recovery from Asymmetric Perceptual Tilt: Evidence from the Subjective Visual Vertical Test

    PubMed Central

    Gnanasegaram, Joshua J.; Parkes, William J.; Cushing, Sharon L.; McKnight, Carmen L.; Papsin, Blake C.; Gordon, Karen A.

    2016-01-01

    Vestibular end organ impairment is highly prevalent in children who have sensorineural hearing loss (SNHL) rehabilitated with cochlear implants (CIs). As a result, spatial perception is likely to be impacted in this population. Of particular interest is the perception of visual vertical because it reflects a perceptual tilt in the roll axis and is sensitive to an imbalance in otolith function. The objectives of the present study were thus to identify abnormalities in perception of the vertical plane in children with SNHL and determine whether such abnormalities could be resolved with stimulation from the CI. Participants included 53 children (15.2 ± 4.0 years of age) with SNHL and vestibular loss, confirmed with vestibular evoked myogenic potential (VEMP) testing. Testing protocol was validated in a sample of nine young adults with normal hearing (28.8 ± 7.7 years). Perception of visual vertical was assessed using the static Subjective Visual Vertical (SVV) test performed with and without stimulation in the participants with cochleovestibular loss. Trains of electrical pulses were delivered by an electrode in the left and/or right ear. Asymmetric spatial orientation deficits were found in nearly half of the participants with CIs (24/53 [45%]). The abnormal perception in this cohort was exacerbated by visual tilts in the direction of their deficit. Electric pulse trains delivered using the CI shifted this abnormal perception towards center (i.e., normal; p = 0.007). Importantly, this benefit was realized regardless of which ear was stimulated. These results suggest a role for CI stimulation beyond the auditory system, in particular, for improving vestibular/balance function. PMID:27679562

  7. Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study

    NASA Astrophysics Data System (ADS)

    Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans

    2015-03-01

    Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.

  8. Theoretical analysis of the pulse-clamp method as applied to neural stimulating electrodes.

    SciTech Connect

    Stefan, I. C.; Tolmachev, Y. V.; Nagy, Z.; Minkoff, M.; Merrill, D. R.; Mortimer, J. T.; Scherson, D. A.; Case Western Reserve Univ.

    2001-02-01

    A mathematical model was developed to simulate potential pulse clamp experiments at inert-electrode/aqueous solution interfaces in the absence of dioxygen or other adventitious redox active species. This model incorporates a potential invariant interfacial capacitor, a kinetically slow redox couple with parameters consistent with the H{sub 2}O/H{sub 2} reaction on polycrystalline Au in acid electrolytes as the only faradaic process involved, and diffusion as the only mode of mass transport in solution phase. Numerical integration of the resulting system of differential equations was found to yield results in good agreement with experimental data reported by Mortimer and co-workers for Au in dearated sulfuric acid solutions. A detailed analysis of these calculations identified the fast and slow recoverable charges to be capacitive and the unrecoverable charges to be faradaic. The results obtained indicated that for small overpotentials the charge is stored in the interfacial capacitor, and that significant faradaic processes occur only when the overpotential is large. Furthermore, during the delay, and despite the fact that no current flows through the external circuit, the capacitor discharges via the faradaic reaction, increasing the total amount of product generated. More importantly, under the conditions selected for the simulations, none of the faradaic charge is recovered during the potential controlled stage of the sequence. These results provide insight into the relationships between stimulus parameters and charge injected into irreversible faradaic reactions, which may generate biologically harmful species. In general, as stimulus pulse durations increase, unrecoverable charge increases. Also, as the delay increases between the end of the primary and beginning of the secondary pulse, unrecoverable charge increases. Furthermore, based on the mathematical model used herein, the use of an electrode material with a small exchange current density would allow

  9. Effects of dopaminergic and subthalamic stimulation on musical performance.

    PubMed

    van Vugt, Floris T; Schüpbach, Michael; Altenmüller, Eckart; Bardinet, Eric; Yelnik, Jérôme; Hälbig, Thomas D

    2013-05-01

    Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

  10. Nonmotor outcomes in Parkinson’s disease: is deep brain stimulation better than dopamine replacement therapy?

    PubMed Central

    Kandadai, Rukmini Mridula; Jabeen, Afshan; Kannikannan, Meena A.

    2012-01-01

    Nonmotor symptoms are an integral part of Parkinson’s disease and cause significant morbidity. Pharmacological therapy helps alleviate the disease but produces nonmotor manifestations. While deep brain stimulation (DBS) has emerged as the treatment of choice for motor dysfunction, the effect on nonmotor symptoms is not well known. Compared with pharmacological therapy, bilateral subthalamic nucleus (STN)-DBS or globus pallidum interna (GPi)-DBS has significant beneficial effects on pain, sleep, gastrointestinal and urological symptoms. STN-DBS is associated with a mild worsening in verbal fluency while GPi-DBS has no effect on cognition. STN-DBS may improve cardiovascular autonomic disturbances by reducing the dose of dopaminergic drugs. Because the motor effects of STN-DBS and GPi-DBS appear to be similar, nonmotor symptoms may determine the target choice in surgery of future patients. PMID:22276074

  11. Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes.

    PubMed

    Wurth, S; Capogrosso, M; Raspopovic, S; Gandar, J; Federici, G; Kinany, N; Cutrone, A; Piersigilli, A; Pavlova, N; Guiet, R; Taverni, G; Rigosa, J; Shkorbatova, P; Navarro, X; Barraud, Q; Courtine, G; Micera, S

    2017-04-01

    Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes

  12. c-Fos expression after deep brain stimulation of the pedunculopontine tegmental nucleus in the rat 6-hydroxydopamine Parkinson model.

    PubMed

    Saryyeva, Assel; Nakamura, Makoto; Krauss, Joachim K; Schwabe, Kerstin

    2011-11-01

    Deep brain stimulation (DBS) is used to alleviate motor dysfunction in Parkinson's disease (PD). The pedunculopontine nucleus (PPN) may be a potential target for severe freezing and postural instability with 25 Hz stimulation being considered more effective than 130 Hz stimulation. Here we evaluated the expression of c-Fos after 25 Hz and 130 Hz DBS of the pedunculopontine tegmental nucleus (PPTg, i.e., the rodent equivalent to the human PPN) in the rat 6-hydroxydopamine (6-OHDA) PD model. Anaesthetized male Sprague Dawley rats with unilateral 6-OHDA-induced nigrostriatal lesions were stimulated with 25 Hz, 130 Hz, or 0 Hz sham-stimulation for 4h by electrodes implanted into the ipsilateral PPTg. Thereafter the distribution and number of neurons expressing the immediate early gene c-Fos, a marker for acute neuronal activity, was assessed. DBS of the PPTg induced strong ipsilateral c-Fos expression at the stimulation site, with 25 Hz having a more marked impact than 130 Hz. Additionally, c-Fos was strongly expressed in the central gray. In the dorsal part expression was stronger after 25 Hz stimulation, while in the medial and ventral part there was no difference between 25 Hz and 130 Hz stimulation. Expression in the basal ganglia was negligible. In the rat 6-OHDA PD model stimulation of the PPTg did not affect c-Fos expression in the basal ganglia, but had a strong impact on other functional circuitries. PPN stimulation in humans might therefore also have an impact on other systems than the motor system.

  13. An inexpensive, charge-balanced rodent deep brain stimulation device: a step-by-step guide to its procurement and construction

    PubMed Central

    Ewing, Samuel G.; Lipski, Witold J.; Grace, Anthony A.; Winter, Christine

    2013-01-01

    Background Despite there being a relatively large number of methods papers which detail specifically the development of stimulation devices, only a small number of reports involve the application of these devices in freely moving animals. To date multiple preclinical neural stimulators have been designed and described but have failed to make an impact on the methods employed by the majority of laboratories studying DBS. Thus, the overwhelming majority of DBS studies are still performed by tethering the subject to an external stimulator. We believe that the low adoption rate of previously described methods is a result of the complexity of replicating and implementing these methods. New Method Here were describe both the design and procurement of a simple and inexpensive stimulator designed to be compatible with commonly used, commercially available electrodes (Plastics 1). Results This system is initially programmable in frequency, pulsewidth and current amplitude, and delivers biphasic, charge-balanced output to two independent electrodes. Comparison with Existing Method(s) It is easy to implement requiring neither subcutaneous implantation or custom-made electrodes and has been optimized for either direct mounting to the head or for use with rodent jackets. Conclusions This device is inexpensive and universally accessible, facilitating high throughput, low cost, long-term rodent deep brain stimulation experiments. PMID:23954265

  14. [A Case of Left Vertebral Artery Aneurysm Showing Evoked Potentials on Bilateral Electrode by the Left Vagus Nerve Stimulation to Electromyographic Tracheal Tube].

    PubMed

    Kadoya, Tatsuo; Uehara, Hirofumi; Yamamoto, Toshinori; Shiraishi, Munehiro; Kinoshita, Yuki; Joyashiki, Takeshi; Enokida, Kengo

    2016-02-01

    Previously, we reported a case of brainstem cavernous hemangioma showing false positive responses to electromyographic tracheal tube (EMG tube). We concluded that the cause was spontaneous respiration accompanied by vocal cord movement. We report a case of left vertebral artery aneurysm showing evoked potentials on bilateral electrodes by the left vagus nerve stimulation to EMG tube. An 82-year-old woman underwent clipping of a left unruptured vertebral artery-posterior inferior cerebellar artery aneurysm. General anesthesia was induced with remifentanil, propofol and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord. When the manipulation reached brainstem and the instrument touched the left vagus nerve, evoked potentials appeared on bilateral electrodes. EMG tube is equipped with two electrodes on both sides. We concluded that the left vagus nerve stimulation generated evoked potentials of the left laryngeal muscles, and they were simultaneously detected as potential difference between two electrodes on both sides. EMG tube is used to identify the vagus nerve. However, it is necessary to bear in mind that each vagus nerve stimulation inevitably generates evoked potentials on bilateral electrodes.

  15. The impact of deep brain stimulation on tinnitus

    PubMed Central

    Smit, Jasper V.; Janssen, Marcus L. F.; Engelhard, Malou; de Bie, Rob M. A.; Schuurman, P. Richard; Contarino, Maria F.; Mosch, Arne; Temel, Yasin; Stokroos, Robert J.

    2016-01-01

    Background: Tinnitus is a disorder of the nervous system that cannot be adequately treated with current therapies. The effect of neuromodulation induced by deep brain stimulation (DBS) on tinnitus has not been studied well. This study investigated the effect of DBS on tinnitus by use of a multicenter questionnaire study. Methods: Tinnitus was retrospectively assessed prior to DBS and at the current situation (with DBS). From the 685 questionnaires, 443 were returned. A control group was one-to-one matched to DBS patients who had tinnitus before DBS (n = 61). Tinnitus was assessed by the tinnitus handicap inventory (THI) and visual analog scales (VAS) of loudness and burden. Results: The THI decreased significantly during DBS compared to the situation prior to surgery (from 18.9 to 15.1, P < .001), which was only significant for DBS in the subthalamic nucleus (STN). The THI in the control group (36.9 to 35.5, P = 0.50) and other DBS targets did not change. The VAS loudness increased in the control group (5.4 to 6.0 P < .01). Conclusion: DBS might have a modulatory effect on tinnitus. Our study suggests that DBS of the STN may have a beneficial effect on tinnitus, but most likely other nuclei linked to the tinnitus circuitry might be even more effective. PMID:27994936

  16. Sensitivity of temporal excitation properties to the neuronal element activated by extracellular stimulation.

    PubMed

    Miocinovic, Svjetlana; Grill, Warren M

    2004-01-15

    Measurements of the chronaxies and refractory periods with extracellular stimuli have been used to conclude that large diameter axons are responsible for the effects of deep brain stimulation (DBS). We hypothesized that because action potential initiation by extracellular stimulation occurs in the axons of central nervous system (CNS) neurons, the chronaxies and refractory periods determined using extracellular stimulation would be similar for cells and axons. Computer simulation was used to determine the sensitivity of chronaxie and refractory period to the neural element stimulated. The results demonstrate that chronaxies and refractory periods were dependent on the polarity of the extracellular stimulus and the electrode-to-neuron distance, and indicate that there is little systematic difference in either chronaxies or refractory periods between local cells or axons of passage with extracellular stimulation. This finding points out the difficulty in drawing conclusions regarding which neuronal elements are activated based on extracellular measurements of temporal excitation properties.

  17. Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

    PubMed Central

    Chaturvedi, Ashutosh; Foutz, Thomas J.; McIntyre, Cameron C.

    2012-01-01

    Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson’s disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multi-compartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side-effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology. PMID:22277548

  18. The Safety of Using Body-Transmit MRI in Patients with Implanted Deep Brain Stimulation Devices

    PubMed Central

    Kahan, Joshua; Papadaki, Anastasia; White, Mark; Mancini, Laura; Yousry, Tarek; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Thornton, John

    2015-01-01

    Background Deep brain stimulation (DBS) is an established treatment for patients with movement disorders. Patients receiving chronic DBS provide a unique opportunity to explore the underlying mechanisms of DBS using functional MRI. It has been shown that the main safety concern with MRI in these patients is heating at the electrode tips – which can be minimised with strict adherence to a supervised acquisition protocol using a head-transmit/receive coil at 1.5T. MRI using the body-transmit coil with a multi-channel receive head coil has a number of potential advantages including an improved signal-to-noise ratio. Study outline We compared the safety of cranial MRI in an in vitro model of bilateral DBS using both head-transmit and body-transmit coils. We performed fibre-optic thermometry at a Medtronic ActivaPC device and Medtronic 3389 electrodes during turbo-spin echo (TSE) MRI using both coil arrangements at 1.5T and 3T, in addition to gradient-echo echo-planar fMRI exposure at 1.5T. Finally, we investigated the effect of transmit-coil choice on DBS stimulus delivery during MRI. Results Temperature increases were consistently largest at the electrode tips. Changing from head- to body-transmit coil significantly increased the electrode temperature elevation during TSE scans with scanner-reported head SAR 0.2W/kg from 0.45°C to 0.79°C (p<0.001) at 1.5T, and from 1.25°C to 1.44°C (p<0.001) at 3T. The position of the phantom relative to the body coil significantly impacted on electrode heating at 1.5T; however, the greatest heating observed in any position tested remained <1°C at this field strength. Conclusions We conclude that (1) with our specific hardware and SAR-limited protocol, body-transmit cranial MRI at 1.5T does not produce heating exceeding international guidelines, even in cases of poorly positioned patients, (2) cranial MRI at 3T can readily produce heating exceeding international guidelines, (3) patients with ActivaPC Medtronic systems are safe

  19. Fiber tractography of the axonal pathways linking the basal ganglia and cerebellum in Parkinson disease: implications for targeting in deep brain stimulation

    PubMed Central

    Sweet, Jennifer A.; Walter, Benjamin L.; Gunalan, Kabilar; Chaturvedi, Ashutosh; Mcintyre, Cameron C.; Miller, Jonathan P.

    2015-01-01

    Object Stimulation of white matter pathways near targeted structures may contribute to therapeutic effects of deep brain stimulation (DBS) for patients with Parkinson disease (PD). Two tracts linking the basal ganglia and cerebellum have been described in primates: the subthalamopontocerebellar tract (SPCT) and the dentatothalamic tract (DTT). The authors used fiber tractography to evaluate white matter tracts that connect the cerebellum to the region of the basal ganglia in patients with PD who were candidates for DBS. Methods Fourteen patients with advanced PD underwent 3-T MRI, including 30-directional diffusion-weighted imaging sequences. Diffusion tensor tractography was performed using 2 regions of interest: ipsilateral subthalamic and red nuclei, and contralateral cerebellar hemisphere. Nine patients underwent subthalamic DBS, and the course of each tract was observed relative to the location of the most effective stimulation contact and the volume of tissue activated. Results In all patients 2 distinct tracts were identified that corresponded closely to the described anatomical features of the SPCT and DTT, respectively. The mean overall distance from the active contact to the DTT was 2.18 ± 0.35 mm, and the mean proportional distance relative to the volume of tissue activated was 1.35 ± 0.48. There was a nonsignificant trend toward better postoperative tremor control in patients with electrodes closer to the DTT. Conclusions The SPCT and the DTT may be related to the expression of symptoms in PD, and this may have implications for DBS targeting. The use of tractography to identify the DTT might assist with DBS targeting in the future. PMID:24484226

  20. Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode

    NASA Astrophysics Data System (ADS)

    Jensen, Ralph J.; Ziv, Ofer R.; Rizzo, Joseph F.

    2005-03-01

    Rational selection of electrical stimulus parameters for an electronic retinal prosthesis requires knowledge of the electrophysiological responses of retinal neurons to electrical stimuli. In this study, we examined the effects of cathodal and anodal current pulses on the extracellularly recorded responses of OFF and ON rabbit retinal ganglion cells (RGCs) in an in vitro preparation. Current pulses (1 msec duration), delivered by a 125 µm electrode placed on the inner retinal surface within the receptive field of a RGC, produced both short-latency (<=5 msec) and long-latency (8-60 msec) responses. The long-latency responses, but not the short-latency responses, were abolished upon application of the glutamate receptor antagonists CNQX and NBQX, thus indicating that the long-latency responses of RGCs are due to activation of presynaptic neurons in the retina. The latency of the long-latency response depended upon the polarity of the stimulus. For OFF RGCs, the average latency was 11 msec for a cathodal stimulus and 24 msec for an anodal stimulus. For ON RGCs, the average latency was 25 msec for a cathodal stimulus and 16 msec for an anodal stimulus. The threshold current also depended upon the polarity of the stimulus, at least for OFF RGCs. The average threshold current for evoking a long-latency response in OFF RGCs was 10 µA for a cathodal stimulus and 21 µA for an anodal stimulus. In ON RGCs, the average threshold current was 13 µA for a cathodal stimulus and 15 µA for an anodal stimulus.

  1. Mediodorsal thalamic stimulation is not protective against seizures induced by amygdaloid kindling in rats.

    PubMed

    Wang, Shuang; Wu, Deng-Chang; Fan, Xiao-Ning; Zhu, Mei-Zhen; Hu, Qiong-Yao; Zhou, Dong; Ding, Mei-Ping; Chen, Zhong

    2010-09-06

    Deep brain stimulation (DBS) is now emerging as a new option for treating intractable epilepsy. Cumulative studies suggest that the mediodorsal thalamic nucleus (MD) is involved in limbic seizure activity. This study aims to investigate whether DBS of the MD can protect against seizures induced by amygdaloid kindling. We studied the effect of low-frequency stimulation (LFS, 1 Hz) or high-frequency stimulation (HFS, 100 Hz) in the MD on amygdaloid kindling seizures. During the kindling acquisition, DBS in the MD was daily administered immediately after the kindling stimulus or before the kindling stimulus (preemptive DBS). The effects of both post-treatment of DBS and preemptive DBS in the MD on the expression of amygdaloid kindling seizures were evaluated. We found the DBS or preemptive DBS in the MD, either LFS or HFS, did not significantly change the rate of amygdaloid kindling. Similarly, DBS or preemptive DBS in the MD did not significantly change any parameters representing the expression of amygdaloid kindling. Our study suggests that DBS in the MD may have no significant effect on limbic seizures.

  2. Electrical stimulation using conductive polymer polypyrrole promotes differentiation of human neural stem cells: a biocompatible platform for translational neural tissue engineering.

    PubMed

    Stewart, Elise; Kobayashi, Nao R; Higgins, Michael J; Quigley, Anita F; Jamali, Sina; Moulton, Simon E; Kapsa, Robert M I; Wallace, Gordon G; Crook, Jeremy M

    2015-04-01

    Conductive polymers (CPs) are organic materials that hold great promise for biomedicine. Potential applications include in vitro or implantable electrodes for excitable cell recording and stimulation and conductive scaffolds for cell support and tissue engineering. In this study, we demonstrate the utility of electroactive CP polypyrrole (PPy) containing the anionic dopant dodecylbenzenesulfonate (DBS) to differentiate novel clinically relevant human neural stem cells (hNSCs). Electrical stimulation of PPy(DBS) induced hNSCs to predominantly β-III Tubulin (Tuj1) expressing neurons, with lower induction of glial fibrillary acidic protein (GFAP) expressing glial cells. In addition, stimulated cultures comprised nodes or clusters of neurons with longer neurites and greater branching than unstimulated cultures. Cell clusters showed a similar spatial distribution to regions of higher conductivity on the film surface. Our findings support the use of electrical stimulation to promote neuronal induction and the biocompatibility of PPy(DBS) with hNSCs and opens up the possibility of identifying novel mechanisms of fate determination of differentiating human stem cells for advanced in vitro modeling, translational drug discovery, and regenerative medicine.

  3. Web-Based Telemonitoring and Delivery of Caregiver Support for Patients With Parkinson Disease After Deep Brain Stimulation: Protocol

    PubMed Central

    Rossi, Elena; Rosa, Manuela; Cogiamanian, Filippo; Rossi, Lorenzo; Bertolasi, Laura; Vogrig, Alberto; Pinciroli, Francesco; Barbieri, Sergio; Priori, Alberto

    2015-01-01

    Background The increasing number of patients, the high costs of management, and the chronic progress of the disease that prevents patients from performing even simple daily activities make Parkinson disease (PD) a complex pathology with a high impact on society. In particular, patients implanted with deep brain stimulation (DBS) electrodes face a highly fragile stabilization period, requiring specific support at home. However, DBS patients are followed usually by untrained personnel (caregivers or family), without specific care pathways and supporting systems. Objective This projects aims to (1) create a reference consensus guideline and a shared requirements set for the homecare and monitoring of DBS patients, (2) define a set of biomarkers that provides alarms to caregivers for continuous home monitoring, and (3) implement an information system architecture allowing communication between health care professionals and caregivers and improving the quality of care for DBS patients. Methods The definitions of the consensus care pathway and of caregiver needs will be obtained by analyzing the current practices for patient follow-up through focus groups and structured interviews involving health care professionals, patients, and caregivers. The results of this analysis will be represented in a formal graphical model of the process of DBS patient care at home. To define the neurophysiological biomarkers to be used to raise alarms during the monitoring process, neurosignals will be acquired from DBS electrodes through a new experimental system that records while DBS is turned ON and transmits signals by radiofrequency. Motor, cognitive, and behavioral protocols will be used to study possible feedback/alarms to be provided by the system. Finally, a set of mobile apps to support the caregiver at home in managing and monitoring the patient will be developed and tested in the community of caregivers that participated in the focus groups. The set of developed apps will be

  4. Engineering the Next Generation of Clinical Deep Brain Stimulation Technology

    PubMed Central

    McIntyre, Cameron C.; Chaturvedi, Ashutosh; Shamir, Reuben R.; Lempka, Scott F.

    2014-01-01

    Deep brain stimulation (DBS) has evolved into a powerful clinical therapy for a range of neurological disorders, but even with impressive clinical growth, DBS technology has been relatively stagnant over its history. However, enhanced collaborations between neural engineers, neuroscientists, physicists, neurologists, and neurosurgeons are beginning to address some of the limitations of current DBS technology. These interactions have helped to develop novel ideas for the next generation of clinical DBS systems. This review attempts collate some of that progress and with two goals in mind. First, provide a general description of current clinical DBS practices, geared toward educating biomedical engineers and computer scientists on a field that needs their expertise and attention. Second, describe some of the technological developments that are currently underway in surgical targeting, stimulation parameter selection, stimulation protocols, and stimulation hardware that are being directly evaluated for near term clinical application. PMID:25161150

  5. Engineering the next generation of clinical deep brain stimulation technology.

    PubMed

    McIntyre, Cameron C; Chaturvedi, Ashutosh; Shamir, Reuben R; Lempka, Scott F

    2015-01-01

    Deep brain stimulation (DBS) has evolved into a powerful clinical therapy for a range of neurological disorders, but even with impressive clinical growth, DBS technology has been relatively stagnant over its history. However, enhanced collaborations between neural engineers, neuroscientists, physicists, neurologists, and neurosurgeons are beginning to address some of the limitations of current DBS technology. These interactions have helped to develop novel ideas for the next generation of clinical DBS systems. This review attempts collate some of that progress with two goals in mind. First, provide a general description of current clinical DBS practices, geared toward educating biomedical engineers and computer scientists on a field that needs their expertise and attention. Second, describe some of the technological developments that are currently underway in surgical targeting, stimulation parameter selection, stimulation protocols, and stimulation hardware that are being directly evaluated for near term clinical application.

  6. The Present Indication and Future of Deep Brain Stimulation

    PubMed Central

    SUGIYAMA, Kenji; NOZAKI, Takao; ASAKAWA, Tetsuya; KOIZUMI, Shinichiro; SAITOH, Osamu; NAMBA, Hiroki

    2015-01-01

    The use of electrical stimulation to treat pain in human disease dates back to ancient Rome or Greece. Modern deep brain stimulation (DBS) was initially applied for pain treatment in the 1960s, and was later used to treat movement disorders in the 1990s. After recognition of DBS as a therapy for central nervous system (CNS) circuit disorders, DBS use showed drastic increase in terms of adaptability to disease and the patient’s population. More than 100,000 patients have received DBS therapy worldwide. The established indications for DBS are Parkinson’s disease, tremor, and dystonia, whereas global indications of DBS expanded to other neuronal diseases or disorders such as neuropathic pain, epilepsy, and tinnitus. DBS is also experimentally used to manage cognitive disorders and psychiatric diseases such as major depression, obsessive-compulsive disorder (OCD), Tourette’s syndrome, and eating disorders. The importance of ethics and conflicts surrounding the regulation and freedom of choice associated with the application of DBS therapy for new diseases or disorders is increasing. These debates are centered on the use of DBS to treat new diseases and disorders as well as its potential to enhance ability in normal healthy individuals. Here we present three issues that need to be addressed in the future: (1) elucidation of the mechanisms of DBS, (2) development of new DBS methods, and (3) miniaturization of the DBS system. With the use of DBS, functional neurosurgery entered into the new era that man can manage and control the brain circuit to treat intractable neuronal diseases and disorders. PMID:25925757

  7. A novel assistive method for rigidity evaluation during deep brain stimulation surgery using acceleration sensors.

    PubMed

    Shah, Ashesh; Coste, Jérôme; Lemaire, Jean-Jacques; Schkommodau, Erik; Taub, Ethan; Guzman, Raphael; Derost, Philippe; Hemm, Simone

    2016-12-16

    OBJECTIVE Despite the widespread use of deep brain stimulation (DBS) for movement disorders such as Parkinson's disease (PD), the exact anatomical target responsible for the therapeutic effect is still a subject of research. Intraoperative stimulation tests by experts consist of performing passive movements of the patient's arm or wrist while the amplitude of the stimulation current is increased. At each position, the amplitude that best alleviates rigidity is identified. Intrarater and interrater variations due to the subjective and semiquantitative nature of such evaluations have been reported. The aim of the present study was to evaluate the use of an acceleration sensor attached to the evaluator's wrist to assess the change in rigidity, hypothesizing that such a change will alter the speed of the passive movements. Furthermore, the combined analysis of such quantitative results with anatomy would generate a more reproducible description of the most effective stimulation sites. METHODS To test the reliability of the method, it was applied during postoperative follow-up examinations of 3 patients. To study the feasibility of intraoperative use, it was used during 9 bilateral DBS operations in patients suffering from PD. Changes in rigidity were calculated by extracting relevant outcome measures from the accelerometer data. These values were used to identify rigidity-suppressing stimulation current amplitudes, which were statistically compared with the amplitudes identified by the neurologist. Positions for the chronic DBS lead implantation that would have been chosen based on the acceleration data were compared with clinical choices. The data were also analyzed with respect to the anatomical location of the stimulating electrode. RESULTS Outcome measures extracted from the accelerometer data were reproducible for the same evaluator, thus providing a reliable assessment of rigidity changes during intraoperative stimulation tests. Of the 188 stimulation sites

  8. Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration

    PubMed Central

    Ellefsen, Kayla N; da Costa, Jose Luiz; Concheiro, Marta; Anizan, Sebastien; Barnes, Allan J; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2015-01-01

    Background: DBS are an increasingly common clinical matrix. Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC–HRMS and 2D GC–MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens’ (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4–105.9 %CV) and were lower than in blood. Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed. PMID:26327184

  9. Thalamotomy-Like Effects From Partial Removal of a Ventral Intermediate Nucleus Deep Brain Stimulator Lead in a Patient With Essential Tremor: Case Report

    PubMed Central

    Rolston, John D.; Ramos, Alexander D.; Heath, Susan; Englot, Dario J.; Lim, Daniel A.

    2017-01-01

    BACKGROUND AND IMPORTANCE The ventral intermediate nucleus of the thalamus is a primary target of deep brain stimulation (DBS) in patients with essential tremor. Despite reliable control of contralateral tremor, there is sometimes a need for lead revision in cases of infection, hardware malfunction, or failure to relieve symptoms. Here, we present the case of a patient undergoing revision after ventral intermediate nucleus (Vim) DBS failed to control his tremor. During the electrode removal, the distal portion of the lead was found to be tightly adherent to tissue within the deep brain. Partial removal of the electrode in turn caused weakness, paresthesias, and tremor control similar to the effects produced by thalamotomy or thalamic injury. CLINICAL PRESENTATION A 48-year-old man with essential tremor had bilateral Vim DBS leads implanted 10 years earlier but had poor control of his tremor and ultimately opted for surgical revision with lead placement in the zona incerta. During attempted removal of his right lead, the patient became somnolent with contralateral weakness and paresthesias. The procedure was aborted, and postoperative neuroimaging was immediately obtained, showing no signs of stroke or hemorrhage. The patient had almost complete control of his left arm tremor postoperatively, and his weakness soon resolved. CONCLUSION To the best of our knowledge, this is the first reported case of cerebral injury after DBS revision and offers insights into the mechanism of high-frequency electric stimulation compared with lesions. That is, although high-frequency stimulation failed to control this patient’s tremor, thalamotomy-like injury was completely effective. PMID:26200771

  10. High-voltage VIM Region Deep Brain Stimulation Mimicking Progressive Supranuclear Palsy

    PubMed Central

    Patterson, Addie; Okun, Michael S.; Hess, Christopher

    2017-01-01

    Background Deep brain stimulation (DBS) for essential tremor (ET) can cause unwanted side effects. Case Report A patient with ET underwent unilateral dual-lead thalamic DBS. He later developed parkinsonism with atypical features and was diagnosed with progressive supranuclear palsy. During presentation for a second opinion, stimulation-induced side effects were suspected. Inactivation of DBS resolved atypical features and superimposed idiopathic Parkinson disease (PD) was diagnosed. Discussion This case illustrates the importance of recognizing the possible influence of stimulation-induced side effects and discusses when to utilize dual-lead DBS for ET and the co-occurrence of ET and PD. PMID:28373925

  11. Modulating Endogenous Electric Currents in Human Corneal Wounds—A Novel Approach of Bioelectric Stimulation Without Electrodes

    PubMed Central

    Reid, Brian; Graue-Hernandez, Enrique O.; Mannis, Mark J.; Zhao, Min

    2011-01-01

    Purpose To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Methods Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Results Unwounded cornea had small outward currents (0.07 μA/cm2). Wounding increased the current more than 5 fold (0.41 μA/cm2). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Conclusions Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients. PMID:21099404

  12. Probing the human brain with stimulating electrodes: the story of Roberts Bartholow's (1874) experiment on Mary Rafferty.

    PubMed

    Harris, Lauren Julius; Almerigi, Jason B

    2009-06-01

    Roberts Bartholow's 1874 experiment on Mary Rafferty is widely cited as the first demonstration, by direct application of stimulating electrodes, of the motor excitability of the human cerebral cortex. The many accounts of the experiment, however, leave certain questions and details unexamined or unresolved, especially about Bartholow's goals, the nature and quality of the evidence, and the experiment's role in the history of theory and research on localisation of function. In this article, we try to fill these gaps and to tell the full story. We describe Bartholow's career up to 1874, review the theoretical and empirical background for the experiment, and present Bartholow's own account of the experiment as well as those of his supporters and critics. We then present our own analysis, assess the experiment's influence on contemporaneous scientific opinion about cortical excitability, and trace its citation record into our own time. We also review and assess ethical criticisms of Bartholow and their effects on his career, and we close by discussing the role we think the experiment deserves to play in the history of theory and research on cortical excitability.

  13. Facilitating effects of deep brain stimulation on feedback learning in Parkinson's disease.

    PubMed

    Meissner, Sarah Nadine; Südmeyer, Martin; Keitel, Ariane; Pollok, Bettina; Bellebaum, Christian

    2016-10-15

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides an effective treatment for Parkinson's disease (PD) motor symptoms. However, findings of effects on cognitive function such as feedback learning remain controversial and rare. The aim of the present study was to gain a better understanding of cognitive alterations associated with STN-DBS. Therefore, we investigated effects of STN-DBS on active and observational feedback learning in PD. 18 PD patients with STN-DBS and 18 matched healthy controls completed active and observational feedback learning tasks. Patients were investigated ON and OFF STN-DBS. Tasks consisted of learning (with feedback) and test phases (without feedback). STN-DBS improved active learning during feedback trials and PD patients ON (but not OFF) STN-DBS showed comparable performance patterns as healthy controls. No STN-DBS effect was found when assessing performance during active test trials without feedback. In this case, however, STN-DBS effects were found to depend on symptom severity. While more impaired patients benefited from STN-DBS, stimulation had no facilitating effect on patients with less severe symptoms. Along similar lines, the severity of motor symptoms tended to be significantly correlated with differences in active test performance due to STN-DBS. For observational feedback learning, there was a tendency for a positive STN-DBS effect with patients reaching the performance level of healthy controls only ON STN-DBS. The present data suggest that STN-DBS facilitates active feedback learning in PD patients. Furthermore, they provide first evidence that STN-DBS might not only affect learning from own but also from observed actions and outcomes.

  14. Short Pauses in Thalamic Deep Brain Stimulation Promote Tremor and Neuronal Bursting

    PubMed Central

    Swan, Brandon D.; Brocker, David T.; Hilliard, Justin D.; Tatter, Stephen B.; Gross, Robert E.; Turner, Dennis A.; Grill, Warren M.

    2015-01-01

    Objective We conducted intraoperative measurements of tremor during DBS containing short pauses (≤50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. Methods Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. Results All patterns of DBS decreased tremor relative to ‘off’. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. Conclusion The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. Significance Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor. PMID:26330131

  15. Current Topics in Deep Brain Stimulation for Parkinson Disease

    PubMed Central

    UMEMURA, Atsushi; OYAMA, Genko; SHIMO, Yasushi; NAKAJIMA, Madoka; NAKAJIMA, Asuka; JO, Takayuki; SEKIMOTO, Satoko; ITO, Masanobu; MITSUHASHI, Takumi; HATTORI, Nobutaka; ARAI, Hajime

    2016-01-01

    There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology. PMID:27349658

  16. The Use of Deep Brain Stimulation in Tourette Syndrome

    PubMed Central

    Akbarian-Tefaghi, Ladan; Zrinzo, Ludvic; Foltynie, Thomas

    2016-01-01

    Tourette syndrome (TS) is a childhood neurobehavioural disorder, characterised by the presence of motor and vocal tics, typically starting in childhood but persisting in around 20% of patients into adulthood. In those patients who do not respond to pharmacological or behavioural therapy, deep brain stimulation (DBS) may be a suitable option for potential symptom improvement. This manuscript attempts to summarise the outcomes of DBS at different targets, explore the possible mechanisms of action of DBS in TS, as well as the potential of adaptive DBS. There will also be a focus on the future challenges faced in designing optimized trials. PMID:27548235

  17. Effect of chronic pallidal deep brain stimulation on off period dystonia and sensory symptoms in advanced Parkinson's disease

    PubMed Central

    Loher, T; Burgunder, J; Weber, S; Sommerhalder, R; Krauss, J

    2002-01-01

    Objective: To investigate the efficacy of chronic pallidal deep brain stimulation (DBS) on off period dystonia, cramps, and sensory symptoms in advanced Parkinson's disease (PD). Methods: 16 patients (6 women, 10 men; mean age at surgery 65 years) suffering from advanced PD were followed up prospectively for one year after implantation of a monopolar electrode in the posteroventral lateral globus pallidus internus. Unilateral DBS was performed in 9 patients. 10 patients had bilateral procedures (contemporaneous bilateral surgery in 7 and staged bilateral surgery in 3 instances). The decision whether to perform unilateral or bilateral surgery depended on the clinical presentation of the patient. Patients were formally assessed preoperatively, at 3–5 days, 3 months, and 12 months after surgery. Results: In patients who underwent unilateral surgery, pain was present in 7 (78%), off dystonia in 5 (56%), cramps in 6 (67%), and dysaesthesia in 4 (44%). In patients who underwent bilateral surgery, pain was present in 7 (70%), off dystonia in 6 (60%), cramps in 7 (70%), and dysaesthesia in 4 (40%). With unilateral DBS, contralateral off period dystonia was improved by 100% at 1 year postoperatively, pain by 74%, cramps by 88%, and dysaesthesia by 100%. There was less pronounced amelioration of ipsilateral off period dystonia and sensory symptoms. With bilateral DBS, total scores for dystonia were improved by 86%, for pain by 90%, for cramps by 90%, and for dysaesthesia by 88%. The benefit appeared early at the first evaluation 3–5 days after surgery and was stable throughout the follow up period. Conclusions: Pallidal DBS yields major improvement of off period dystonia, cramps, and sensory symptoms in patients with advanced PD. PMID:12235307

  18. Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Unipolar and Bipolar Depression

    PubMed Central

    Holtzheimer, Paul E.; Kelley, Mary E.; Gross, Robert E.; Filkowski, Megan M.; Garlow, Steven J.; Barrocas, Andrea; Wint, Dylan; Craighead, Margaret C.; Kozarsky, Julie; Chismar, Ronald; Moreines, Jared L.; Mewes, Klaus; Posse, Patricio Riva; Gutman, David A.; Mayberg, Helen S.

    2015-01-01

    Context Deep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited. Objective To assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar II disorder (BP). Design Open-label trial with a sham lead-in phase. Setting Academic medical center. Patients Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation. Main Outcome Measures Change in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation. Results A significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n=17), 5 (36%) and 5 (36%) after 1 year (n=14), and 7 (58%) and 11 (92%) after 2 years (n=12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase

  19. Deep brain stimulation for other tremors, myoclonus, and chorea.

    PubMed

    Starr, Philip A

    2013-01-01

    Deep brain stimulation (DBS) is a well established treatment for essential tremor and for the tremor associated with Parkinson's disease. The efficacy of DBS in these common tremors has led some investigators to apply the technique to rarer tremors such as such as Holmes' tremor, posttraumatic tremor, orthostatic tremor, and the tremor associated with multiple sclerosis. Likewise, DBS of the thalamus and globus pallidus directly suppresses levodopa-induced dyskinesias in Parkinson's disease, suggesting the application of DBS to other hyperkinetic states such as Huntington's disease, tardive dyskinesia, and hemiballism. Myoclonus has also been treated with DBS, especially in cases where it is associated with dystonia. This chapter reviews the reported results of DBS for these conditions. Due to the rarity of these indications, most of the literature reviewed takes the form of case reports or small single-center case series.

  20. Post-operative assessment in Deep Brain Stimulation based on multimodal images: registration workflow and validation

    NASA Astrophysics Data System (ADS)

    Lalys, Florent; Haegelen, Claire; Abadie, Alexandre; Jannin, Pierre

    2009-02-01

    Object Movement disorders in Parkinson disease patients may require functional surgery, when medical therapy isn't effective. In Deep Brain Stimulation (DBS) electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). This paper describes successive steps for constructing a digital Atlas gathering patient's location of electrodes and contacts for post operative assessment. Materials and Method 12 patients who had undergone bilateral STN DBS have participated to the study. Contacts on post-operative CT scans were automatically localized, based on black artefacts. For each patient, post operative CT images were rigidly registered to pre operative MR images. Then, pre operative MR images were registered to a MR template (super-resolution Collin27 average MRI template). This last registration was the combination of global affine, local affine and local non linear registrations, respectively. Four different studies were performed in order to validate the MR patient to template registration process, based on anatomical landmarks and clinical scores (i.e., Unified Parkinson's disease rating Scale). Visualisation software was developed for displaying into the template images the stimulated contacts represented as cylinders with a colour code related to the improvement of the UPDRS. Results The automatic contact localization algorithm was successful for all the patients. Validation studies for the registration process gave a placement error of 1.4 +/- 0.2 mm and coherence with UPDRS scores. Conclusion The developed visualization tool allows post-operative assessment for previous interventions. Correlation with additional clinical scores will certainly permit to learn more about DBS and to better understand clinical side-effects.

  1. Suppression of axonal conduction by sinusoidal stimulation in rat hippocampus in vitro

    NASA Astrophysics Data System (ADS)

    Jensen, A. L.; Durand, D. M.

    2007-06-01

    Deep brain stimulation (DBS), also known as high frequency stimulation (HFS), is a well-established therapy for Parkinson's disease and essential tremor, and shows promise for the therapeutic control of epilepsy. However, the direct effect of DBS on neural elements close to the stimulating electrode remains an important unanswered question. Computational studies have suggested that HFS has a dual effect on neural elements inhibiting cell bodies, while exciting axons. Prior experiments have shown that sinusoidal HFS (50 Hz) can suppress synaptic and non-synaptic cellular activity in several in vitro epilepsy models, in all layers of the hippocampus. However, the effects of HFS on axons near the electrode are still unclear. In the present study, we tested the hypothesis that HFS suppresses axonal conduction in vitro. Sinusoidal HFS was applied to the alvear axon field of transverse rat hippocampal slices. The results show that HFS suppresses the alvear compound action potential (CAP) as well as the CA1 antidromic evoked potential (AEP). Complete suppression was observed as a 100% reduction in the amplitude of the evoked field potential for the duration of the stimulus. Evoked potential width and latency were not significantly affected by sinusoidal HFS. Suppression was dependent on HFS amplitude and frequency, but independent of stimulus duration and synaptic transmission. The frequency dependence of sinusoidal HFS is similar to that observed in clinical DBS, with maximal suppression between 50 and 200 Hz. HFS produced not only suppression of axonal conduction but also a correlated rise in extracellular potassium. These data provide new insights into the effects of HFS on neuronal elements, and show that HFS can block axonal activity through non-synaptic mechanisms.

  2. Suppression of axonal conduction by sinusoidal stimulation in rat hippocampus in vitro.

    PubMed

    Jensen, A L; Durand, D M

    2007-06-01

    Deep brain stimulation (DBS), also known as high frequency stimulation (HFS), is a well-established therapy for Parkinson's disease and essential tremor, and shows promise for the therapeutic control of epilepsy. However, the direct effect of DBS on neural elements close to the stimulating electrode remains an important unanswered question. Computational studies have suggested that HFS has a dual effect on neural elements inhibiting cell bodies, while exciting axons. Prior experiments have shown that sinusoidal HFS (50 Hz) can suppress synaptic and non-synaptic cellular activity in several in vitro epilepsy models, in all layers of the hippocampus. However, the effects of HFS on axons near the electrode are still unclear. In the present study, we tested the hypothesis that HFS suppresses axonal conduction in vitro. Sinusoidal HFS was applied to the alvear axon field of transverse rat hippocampal slices. The results show that HFS suppresses the alvear compound action potential (CAP) as well as the CA1 antidromic evoked potential (AEP). Complete suppression was observed as a 100% reduction in the amplitude of the evoked field potential for the duration of the stimulus. Evoked potential width and latency were not significantly affected by sinusoidal HFS. Suppression was dependent on HFS amplitude and frequency, but independent of stimulus duration and synaptic transmission. The frequency dependence of sinusoidal HFS is similar to that observed in clinical DBS, with maximal suppression between 50 and 200 Hz. HFS produced not only suppression of axonal conduction but also a correlated rise in extracellular potassium. These data provide new insights into the effects of HFS on neuronal elements, and show that HFS can block axonal activity through non-synaptic mechanisms.

  3. Regulation of vesicle transport and cell motility by Golgi-localized Dbs

    PubMed Central

    Fitzpatrick, Ethan R; Hu, Tinghui; Ciccarelli, Bryan T; Whitehead, Ian P

    2014-01-01

    DBS/MCF2L has been recently identified as a risk locus for osteoarthritis. It encodes a guanine nucleotide exchange factor (Dbs) that has been shown to regulate both normal and tumor cell motility. In the current study, we have determined that endogenous Dbs is predominantly expressed as 2 isoforms, a 130 kDa form (Dbs-130) that is localized to the Golgi complex, and an 80 kDa form (Dbs-80) that is localized to the endoplasmic reticulum (ER). We have previously described an inhibitor that binds to the RhoGEF domain of Dbs and blocks its transforming activity. Here we show that the inhibitor localizes to the Golgi, where it specifically interacts with Dbs-130. Inhibition of endogenous Dbs-130 activity is associated with reduced levels of activated Cdc42, enlarged Golgi, and resistance to Brefeldin A-mediated Golgi dispersal, suggesting a role for Dbs in vesicle transport. Cells treated with the inhibitor exhibit normal protein transport from the ER to the Golgi, but are defective in transport from the Golgi to the plasma membrane. Inhibition of Dbs-130 in MDA-MB-231 human breast tumor cells limits motility in both transwell and wound healing assays, but appears to have no effect on the organization of the microtubule cytoskeleton. The reduced motility is associated with a failure to reorient the Golgi toward the leading edge. This is consistent with the Golgi localization, and suggests that the Dbs-130 regulates aspects of the secretory pathway that are required to support cell polarization during directed migration. PMID:25483302

  4. Deep Brain Stimulation: Expanding Applications

    PubMed Central

    TEKRIWAL, Anand; BALTUCH, Gordon

    2015-01-01

    For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models. PMID:26466888

  5. Brain stimulation in posttraumatic stress disorder.

    PubMed

    Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A B; Mindes, Janet; A Golier, Julia; Yehuda, Rachel

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

  6. Brittle Dyskinesia Following STN but not GPi Deep Brain Stimulation

    PubMed Central

    Sriram, Ashok; Foote, Kelly D.; Oyama, Genko; Kwak, Joshua; Zeilman, Pam R.; Okun, Michael S.

    2014-01-01

    Background The aim was to describe the prevalence and characteristics of difficult to manage dyskinesia associated with subthalamic nucleus (STN) deep brain stimulation (DBS). A small subset of STN DBS patients experience troublesome dyskinesia despite optimal programming and medication adjustments. This group of patients has been referred to by some practitioners as brittle STN DBS-induced dyskinesia, drawing on comparisons with brittle diabetics experiencing severe blood sugar regulation issues and on a single description by McLellan in 1982. We sought to describe, and also to investigate how often the “brittle” phenomenon occurs in a relatively large DBS practice. Methods An Institutional Review Board-approved patient database was reviewed, and all STN and globus pallidus internus (GPi) DBS patients who had surgery at the University of Florida from July 2002 to July 2012 were extracted for analysis. Results There were 179 total STN DBS patients and, of those, four STN DBS (2.2%) cases were identified as having dyskinesia that could not be managed without the induction of an “off state,” or by the precipitation of a severe dyskinesia despite vigorous stimulation and medication adjustments. Of 75 GPi DBS cases reviewed, none (0%) was identified as having brittle dyskinesia. One STN DBS patient was successfully rescued by bilateral GPi DBS. Discussion Understanding the potential risk factors for postoperative troublesome and brittle dyskinesia may have an impact on the initial surgical target selection (STN vs. GPI) in DBS therapy. Rescue GPi DBS therapy may be a viable treatment option, though more cases will be required to verify this observation. PMID:24932426

  7. Mechanisms of deep brain stimulation

    PubMed Central

    Cheng, Jennifer J.; Eskandar, Emad N.

    2015-01-01

    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. PMID:26510756

  8. Development of a novel biosensor based on a polypyrrole-dodecylbenzene sulphonate (PPy-DBS) film for the determination of amperometric cholesterol.

    PubMed

    Özer, Bayram Oğuz; Çete, Servet

    2017-06-01

    Herein a novel amperometric biosensor based on a conducting polymer with anionic dopant modified electrode was successfully developed for detection of cholesterol. Polypyrrole is deposited on a platinum surface and the sodium dodecylbenzene sulphonate (DBS) ion-doped polypyrrole film was electrochemically prepared by scanning the electrode potential between -0.8 and +0.8 V at a scan rate of 20 mV/s. The present electrochemical biosensor was optimized in terms of working potential, number of cycles, concentrations of monomer, and anionic dopant. Cholesterol oxidase (ChOx) was physically entrapped in PPy-DBS to construct an amperometric cholesterol biosensor. Amperometric determination is based on the electrochemical detection of H2O2 generated in the enzymatic reaction of cholesterol. Kinetic parameters, operational and storage stabilities, pH, and temperature dependencies were determined. Km and Imax were calculated as 0.11 μM and 0.967 nM/min, respectively. The operational stability results showed that 90.0% of the response current was retained after 30 activity assays. Morphology of electrodes was characterized by SEM and AFM. Additionally, contact angle measurements were made with 1 μL water of polymer film and enzyme electrode. As a result, the cholesterol biosensor suggested in this study is easy to prepare and is highly cost-effective. This composite (PPy-DBS) can supply a biocompatible and electrochemical microenvironment for immobilization of the enzyme, making this material a good candidate for the fabrication of highly sensitive and selective cholesterol biosensors.

  9. Emerging subspecialties in neurology: deep brain stimulation and electrical neuro-network modulation.

    PubMed

    Hassan, Anhar; Okun, Michael S

    2013-01-29

    Deep brain stimulation (DBS) is a surgical therapy that involves the delivery of an electrical current to one or more brain targets. This technology has been rapidly expanding to address movement, neuropsychiatric, and other disorders. The evolution of DBS has created a niche for neurologists, both in the operating room and in the clinic. Since DBS is not always deep, not always brain, and not always simply stimulation, a more accurate term for this field may be electrical neuro-network modulation (ENM). Fellowships will likely in future years evolve their scope to include other technologies, and other nervous system regions beyond typical DBS therapy.

  10. The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease.

    PubMed

    Tremblay, Christina; Macoir, Joël; Langlois, Mélanie; Cantin, Léo; Prud'homme, Michel; Monetta, Laura

    2015-02-01

    The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) on different language abilities are still controversial and its impact on high-level language abilities such as metaphor comprehension has been overlooked. The aim of this study was to determine the effects of STN electrical stimulation on metaphor comprehension and language abilities such as lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on metaphor comprehension, lexical decision, word association and verbal fluency tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN stimulation had a significant beneficial effect on motor symptoms in PD. However, this stimulation did not have any effect on metaphor comprehension or any other cognitive ability evaluated in this study. These outcomes suggest that STN stimulation may have dissociable effects on motor and language functions.

  11. Rescue Procedures after Suboptimal Deep Brain Stimulation Outcomes in Common Movement Disorders

    PubMed Central

    Nagy, Adam M.; Tolleson, Christopher M.

    2016-01-01

    Deep brain stimulation (DBS) is a unique, functional neurosurgical therapy indicated for medication refractory movement disorders as well as some psychiatric diseases. Multicontact electrodes are placed in “deep” structures within the brain with targets varying depending on the surgical indication. An implanted programmable pulse generator supplies the electrodes with a chronic, high frequency electrical current that clinically mimics the effects of ablative lesioning techniques. DBS’s efficacy has been well established for its movement disorder indications (Parkinson’s disease, essential tremor, and dystonia). However, clinical outcomes are sometimes suboptimal, even in the absence of common, potentially reversible complications such as hardware complications, infection, poor electrode placement, and poor programming parameters. This review highlights some of the rescue procedures that have been explored in suboptimal DBS cases for Parkinson’s disease, essential tremor, and dystonia. To date, the data is limited and difficult to generalize, but a large majority of published reports demonstrate positive results. The decision to proceed with such treatments should be made on a case by case basis. Larger studies are needed to clearly establish the benefit of rescue procedures and to establish for which patient populations they may be most appropriate. PMID:27740598

  12. Deep Brain Stimulation for Movement Disorders.

    PubMed

    Revell, Maria A

    2015-12-01

    Disruption in the interaction between the central nervous system, nerves, and muscles cause movement disorders. These disorders can negatively affect quality of life. Deep brain stimulation (DBS) has been identified as a therapy for Parkinson disease and essential tremor that has significant advantages compared with medicinal therapies. Surgical intervention for these disorders before DBS included ablative therapies such as thalamotomy and pallidotomy. These procedures were not reversible and did not allow for treatment adjustments. The advent of DBS progressed therapies for significant movement disorders into the realm of being reversible and adjustable based on patient symptoms.

  13. Fabrication of self-expandable NiTi thin film devices with micro-electrode array for bioelectric sensing, stimulation and ablation.

    PubMed

    Bechtold, Christoph; de Miranda, Rodrigo Lima; Chluba, Christoph; Quandt, Eckhard

    2016-12-01

    Self-expandable medical devices provide mechanical functionality at a specific location of the human body and are viable for minimal invasive procedures. Besides radiopaque markers and drug-eluting coatings, next generation self-expandable devices can be equipped with additional functionality, such as conductive and flexible electrodes, which enables chronic recording of bioelectrical signals, stimulating or ablating tissue. This promises new therapeutic options in various medical fields, among them in particular neuromodulation (e.g. deep brain stimulation), BioMEMS, radio frequency ablation, mapping or denervation. However, the fabrication of such multi-functional devices is challenging. For this study we have realized a 35 μm thick, superelastic NiTi thin film stent structure with six isolated electrodes on the outer circumference, each electrode connected to a contact pad at the end of the stent structure, using magnetron sputtering, UV lithography and wet chemical etching. Mechanical and electrical properties of the device during typical loading conditions, i.e. crimping, simulated pulsatile and electrochemical testing, were characterized and reveal promising results. For the fabrication of future multifunctional, minimal invasive medical devices, such as electroceuticals or other intelligent implants, NiTi thin film technology is therefore a versatile alternative to conventional fabrication routes.

  14. Disruption in proprioception from long-term thalamic deep brain stimulation: a pilot study

    PubMed Central

    Semrau, Jennifer A.; Herter, Troy M.; Kiss, Zelma H.; Dukelow, Sean P.

    2015-01-01

    Deep brain stimulation (DBS) is an excellent treatment for tremor and is generally thought to be reversible by turning off stimulation. For tremor, DBS is implanted in the ventrointermedius (Vim) nucleus of the thalamus, a region that relays proprioceptive information for movement sensation (kinaesthesia). Gait disturbances have been observed with bilateral Vim DBS, but the long-term effects on proprioceptive processing are unknown. We aimed to determine whether Vim DBS surgical implantation or stimulation leads to proprioceptive deficits in the upper limb. We assessed two groups of tremor subjects on measures of proprioception (kinaesthesia, position sense) and motor function using a robotic exoskeleton. In the first group (Surgery), we tested patients before and after implantation of Vim DBS, but before DBS was turned on to determine if proprioceptive deficits were inherent to tremor or caused by DBS implantation. In the second group (Stim), we tested subjects with chronically implanted Vim DBS ON and OFF stimulation. Compared to controls, there were no proprioceptive deficits before or after DBS implantation in the Surgery group. Surprisingly, those that received chronic long-term stimulation (LT-stim, 3–10 years) displayed significant proprioceptive deficits ON and OFF stimulation not present in subjects with chronic short-term stimulation (ST-stim, 0.5–2 years). LT-stim had significantly larger variability and reduced workspace area during the position sense assessment. During the kinesthetic assessment, LT-stim made significantly larger directional errors and consistently underestimated the speed of the robot, despite generating normal movement speeds during motor assessment. Chronic long-term Vim DBS may potentially disrupt proprioceptive processing, possibly inducing irreversible plasticity in the Vim nucleus and/or its network connections. Our findings in the upper limb may help explain some of the gait disturbances seen by others following Vim DBS

  15. High frequency stimulation abolishes thalamic network oscillations: an electrophysiological and computational analysis

    NASA Astrophysics Data System (ADS)

    Lee, Kendall H.; Hitti, Frederick L.; Chang, Su-Youne; Lee, Dongchul C.; Roberts, David W.; McIntyre, Cameron C.; Leiter, James C.

    2011-08-01

    Deep brain stimulation (DBS) of the thalamus has been demonstrated to be effective for the treatment of epilepsy. To investigate the mechanism of action of thalamic DBS, we examined the effects of high frequency stimulation (HFS) on spindle oscillations in thalamic brain slices from ferrets. We recorded intracellular and extracellular electrophysiological activity in the nucleus reticularis thalami (nRt) and in thalamocortical relay (TC) neurons in the lateral geniculate nucleus, stimulated the slice using a concentric bipolar electrode, and recorded the level of glutamate within the slice. HFS (100 Hz) of TC neurons generated excitatory post-synaptic potentials, increased the number of action potentials in both TC and nRt neurons, reduced the input resistance, increased the extracellular glutamate concentration, and abolished spindle wave oscillations. HFS of the nRt also suppressed spindle oscillations. In both locations, HFS was associated with significant and persistent elevation in extracellular glutamate levels and suppressed spindle oscillations for many seconds after the cessation of stimulation. We simulated HFS within a computational model of the thalamic network, and HFS also disrupted spindle wave activity, but the suppression of spindle activity was short-lived. Simulated HFS disrupted spindle activity for prolonged periods of time only after glutamate release and glutamate-mediated activation of a hyperpolarization-activated current (Ih) was incorporated into the model. Our results suggest that the mechanism of action of thalamic DBS as used in epilepsy may involve the prolonged release of glutamate, which in turn modulates specific ion channels such as Ih, decreases neuronal input resistance, and abolishes thalamic network oscillatory activity.

  16. Role of adenosine in the antiepileptic effects of deep brain stimulation

    PubMed Central

    Miranda, Maisa F.; Hamani, Clement; de Almeida, Antônio-Carlos G.; Amorim, Beatriz O.; Macedo, Carlos E.; Fernandes, Maria José S.; Nobrega, José N.; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Andersen, Monica L.; Tufik, Sergio; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine. PMID:25324724

  17. [Mechanism of action for deep brain stimulation and electrical neuro-network modulation (ENM)].

    PubMed

    Okun, Michael S; Oyama, Genko

    2013-01-01

    Deep brain stimulation (DBS) has become an important treatment option for carefully screened medication resistant neurological and neuropsychiatric disorders. DBS therapy is not always applied deep to the brain; does not have to be applied exclusively to the brain; and the mechanism for DBS is not simply stimulation of structures. The applications and target locations for DBS devices are rapidly expanding, with many new regions of the brain, spinal cord, peripheral nerves, and muscles now possibly accessed through this technology. We will review the idea of "electrical neuro-network modulation (ENM)"; discuss the importance of the complex neural networks underpinning the effects of DBS; discuss the expansion of brain targets; discuss the use of fiber based targets; and discuss the importance of tailoring DBS therapy to the symptom, rather than the disease.

  18. Comparison of temporal properties of auditory single units in response to cochlear infrared laser stimulation recorded with multi-channel and single tungsten electrodes

    NASA Astrophysics Data System (ADS)

    Tan, Xiaodong; Xia, Nan; Young, Hunter; Richter, Claus-Peter

    2015-02-01

    Auditory prostheses may benefit from Infrared Neural Stimulation (INS) because optical stimulation allows for spatially selective activation of neuron populations. Selective activation of neurons in the cochlear spiral ganglion can be determined in the central nucleus of the inferior colliculus (ICC) because the tonotopic organization of frequencies in the cochlea is maintained throughout the auditory pathway. The activation profile of INS is well represented in the ICC by multichannel electrodes (MCEs). To characterize single unit properties in response to INS, however, single tungsten electrodes (STEs) should be used because of its better signal-to-noise ratio. In this study, we compared the temporal properties of ICC single units recorded with MCEs and STEs in order to characterize the response properties of single auditory neurons in response to INS in guinea pigs. The length along the cochlea stimulated with infrared radiation corresponded to a frequency range of about 0.6 octaves, similar to that recorded with STEs. The temporal properties of single units recorded with MCEs showed higher maximum rates, shorter latencies, and higher firing efficiencies compared to those recorded with STEs. When the preset amplitude threshold for triggering MCE recordings was raised to twice over the noise level, the temporal properties of the single units became similar to those obtained with STEs. Undistinguishable neural activities from multiple sources in MCE recordings could be responsible for the response property difference between MCEs and STEs. Thus, caution should be taken in single unit recordings with MCEs.

  19. State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

    PubMed

    Wagle Shukla, Aparna; Okun, Michael S

    2016-01-01

    Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

  20. Parkinson's disease patients with bilateral subthalamic deep brain stimulation gain weight.

    PubMed

    Macia, Frédéric; Perlemoine, Caroline; Coman, Irène; Guehl, Dominique; Burbaud, Pierre; Cuny, Emmanuel; Gin, Henri; Rigalleau, Vincent; Tison, François

    2004-02-01

    Weight, body mass index (BMI) and energy expenditure/energy intake (EE/EI) was studied in 19 Parkinson's disease (PD) patients after subthalamic deep brain stimulation (STN-DBS) versus 14 nonoperated ones. Operated patients had a significant weight gain (WG, + 9.7 +/- 7 kg) and BMI increase (+ 4.7 kg/m2). The fat mass was higher after STN-DBS. Resting EE (REE; offdrug/ON stimulation) was significantly decreased in STN-DBS patients, while their daily energy expenditure (DEI) was not significantly different. A significant correlation was found among WG, BMI increase, and pre-operative levodopa-equivalent daily dose, their reduction after STN-DBS, and the differential REE related to stimulation and the REE in the offdrug/OFF stimulation condition. In conclusion, STN-DBS in PD induces a significant WG associated with a reduction in REE without DEI adjustment.

  1. Deep Brain Stimulation for Parkinson’s Disease: Recent Trends and Future Direction

    PubMed Central

    FUKAYA, Chikashi; YAMAMOTO, Takamitsu

    2015-01-01

    To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson’s disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed. PMID:25925761

  2. Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report.

    PubMed

    Ho, Allen L; Choudhri, Omar; Sung, C Kwang; DiRenzo, Elizabeth E; Halpern, Casey H

    2015-03-01

    Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS).

  3. Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration.

    PubMed

    Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Yadid, Gal

    2011-01-01

    The lateral habenula (LHb) plays a role in prediction of negative reinforcement, punishment and aversive responses. In the current study, we examined the role that the LHb plays in regulation of negative reward responses and aversion. First, we tested the effect of intervention in LHb activity on sucrose reinforcing behavior. An electrode was implanted into the LHb and rats were trained to self-administer sucrose (20%; 16 days) until at least three days of stable performance were achieved (as represented by the number of active lever presses in self-administration cages). Rats subsequently received deep brain stimulation (DBS) of the LHb, which significantly reduced sucrose self-administration levels. In contrast, lesion of the LHb increased sucrose-seeking behavior, as demonstrated by a delayed extinction response to substitution of sucrose with water. Furthermore, in a modified non-rewarding conditioned-place-preference paradigm, DBS of the LHb led to aversion to the context associated with stimulation of this brain region. We postulate that electrical stimulation of the LHb attenuates positive reward-associated reinforcement by natural substances.

  4. Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study

    PubMed Central

    Alonso, Fabiola; Latorre, Malcolm A.; Göransson, Nathanael; Zsigmond, Peter; Wårdell, Karin

    2016-01-01

    New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode. PMID:27618109

  5. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    PubMed

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life.

  6. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    PubMed Central

    Albaugh, Daniel L.; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  7. Verbal fluency in patients receiving bilateral versus left-sided deep brain stimulation of the subthalamic nucleus for Parkinson's disease.

    PubMed

    Sjöberg, Rickard L; Lidman, Elin; Häggström, Björn; Hariz, Marwan I; Linder, Jan; Fredricks, Anna; Blomstedt, Patric

    2012-05-01

    The purpose of this study was to investigate the relative effects of unilateral (left-sided) versus bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on verbal fluency. To do this, 10 Parkinson's disease patients with predominantly bilateral motor symptoms who received bilateral STN DBS were compared with 6 patients suffering from predominantly unilateral symptoms who received STN DBS on the left side only. The results suggest that unilateral STN DBS of the speech dominant hemisphere is associated with significantly less declines in measures of verbal fluency as compared to bilateral stimulation.

  8. Improved transcranial magnetic stimulation coil design with realistic head modeling

    NASA Astrophysics Data System (ADS)

    Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2013-03-01

    We are investigating Transcranial magnetic stimulation (TMS) as a noninvasive technique based on electromagnetic induction which causes stimulation of the neurons in the brain. TMS can be used as a pain-free alternative to conventional electroconvulsive therapy (ECT) which is still widely implemented for treatment of major depression. Development of improved TMS coils capable of stimulating subcortical regions could also allow TMS to replace invasive deep brain stimulation (DBS) which requires surgical implantation of electrodes in the brain. Our new designs allow new applications of the technique to be established for a variety of diagnostic and therapeutic applications of psychiatric disorders and neurological diseases. Calculation of the fields generated inside the head is vital for the use of this method for treatment. In prior work we have implemented a realistic head model, incorporating inhomogeneous tissue structures and electrical conductivities, allowing the site of neuronal activation to be accurately calculated. We will show how we utilize this model in the development of novel TMS coil designs to improve the depth of penetration and localization of stimulation produced by stimulator coils.

  9. A Low-Power Blocking-Capacitor-Free Charge-Balanced Electrode-Stimulator Chip With Less Than 6 nA DC Error for 1-mA Full-Scale Stimulation.

    PubMed

    Ji-Jon Sit; Sarpeshkar, R

    2007-09-01

    Large dc blocking capacitors are a bottleneck in reducing the size and cost of neural implants. We describe an electrode-stimulator chip that removes the need for large dc blocking capacitors in neural implants by achieving precise charge-balanced stimulation with <6 nA of dc error. For cochlear implant patients, this is well below the industry's safety limit of 25 nA. Charge balance is achieved by dynamic current balancing to reduce the mismatch between the positive and negative phases of current to 0.4%, followed by a shorting phase of at least 1 ms between current pulses to further reduce the charge error. On +6 and -9 V rails in a 0.7-mum AMI high voltage process, the power consumption of a single channel of this chip is 47 muW when biasing power is shared by 16 channels.

  10. A Feasibility Study of Bilateral Anodal Stimulation of the Prefrontal Cortex Using High-Definition Electrodes in Healthy Participants

    PubMed Central

    Xu, Jiansong; Healy, Stephen M.; Truong, Dennis Q.; Datta, Abhishek; Bikson, Marom; Potenza, Marc N.

    2015-01-01

    Transcranial direct current stimulation (tDCS) studies often use one anode to increase cortical excitability in one hemisphere. However, mental processes may involve cortical regions in both hemispheres. This study’s aim was to assess the safety and possible effects on affect and working memory of tDCS using two anodes for bifrontal stimulation. A group of healthy subjects participated in two bifrontal tDCS sessions on two different days, one for real and the other for sham stimulation. They performed a working memory task and reported their affect immediately before and after each tDCS session. Relative to sham, real bifrontal stimulation did not induce significant adverse effects, reduced decrement in vigor-activity during the study session, and did not improve working memory. These preliminary findings suggest that bifrontal anodal stimulation is feasible and safe and may reduce task-related fatigue in healthy participants. Its effects on neuropsychiatric patients deserve further study. PMID:26339204

  11. Early application of deep brain stimulation: clinical and ethical aspects.

    PubMed

    Woopen, Christiane; Pauls, K Amande M; Koy, Anne; Moro, Elena; Timmermann, Lars

    2013-11-01

    Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinson's disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, (1) DBS early in the course of the disease, and (2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome.

  12. Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats

    PubMed Central

    Bambico, F R; Bregman, T; Diwan, M; Li, J; Darvish-Ghane, S; Li, Z; Laver, B; Amorim, B O; Covolan, L; Nobrega, J N; Hamani, C

    2015-01-01

    Chronic ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) improves depressive-like behaviour in rats via serotonergic and neurotrophic-related mechanisms. We hypothesise that, in addition to these substrates, DBS-induced increases in hippocampal neurogenesis may also be involved. Our results show that stress-induced behavioural deficits in the sucrose preference test, forced swim test, novelty-suppressed feeding test (NSFT) and elevated plus maze were countered by chronic vmPFC DBS. In addition, stressed rats receiving stimulation had significant increases in hippocampal neurogenesis, PFC and hippocampal brain-derived neurotrophic factor levels. To block neurogenesis, stressed animals given DBS were injected with temozolomide. Such treatment reversed the anxiolytic-like effect of stimulation in the NSFT without significantly affecting performance in other behavioural tests. Taken together, our findings suggest that neuroplastic changes, including neurogenesis, may be involved in specific anxiolytic effects of DBS without affecting its general antidepressant-like response. PMID:26529427

  13. The pedunculopontine tegmental nucleus: from basic neuroscience to neurosurgical applications: arousal from slices to humans: implications for DBS.

    PubMed

    Garcia-Rill, Edgar; Simon, Christen; Smith, Kristen; Kezunovic, Nebosja; Hyde, James

    2011-10-01

    One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which projects to the thalamus to trigger thalamocortical rhythms and the brainstem to modulate muscle tone and locomotion. The PPN is a posterior midbrain site known to induce locomotion in decerebrate animals when activated at 40-60 Hz, and has become a target for DBS in disorders involving gait deficits. We developed a research program using brainstem slices containing the PPN to study the cellular and molecular organization of this region. We showed that PPN neurons preferentially fire at gamma band frequency (30-60 Hz) when maximally activated, accounting for the effects of electrical stimulation. In addition, we developed the P13 midlatency auditory evoked potential, which is generated by PPN outputs, in freely moving rats. This allows the study of PPN cellular and molecular mechanisms in the whole animal. We also study the P50 midlatency auditory evoked potential, which is the human equivalent of the rodent P13 potential, allowing us to study PPN-related processes detected in vitro, confirmed in the whole animal, and tested in humans. Previous findings on the P50 potential in PD suggest that PPN output in this disorder is overactive. This translational research program led to the discovery of a novel mechanism of sleep-wake control based on electrical coupling, pointing the way to a number of new clinical applications in the development of novel stimulants (e.g., modafinil) and anesthetics. In addition, it provides methods for monitoring therapeutic efficacy of DBS in humans and animal models.

  14. Evaluation of accuracy in frame-based versus fiducial-based registration for stereotaxy in Parkinson's deep electrode implantation

    NASA Astrophysics Data System (ADS)

    Abbasi, Hamid R.; Hariri, Sanaz; Lee, Jeffrey; Martin, David; Hill, B.; Heit, Gary

    2001-05-01

    After several years of levodopa treatment, patients with Parkinson's Disease (PD) can develop difficult-to-control motor fluctuations and levodopa-induced dyskinesias (LID). Surgical options for these medically intractable PD patients include deep nucleus lesioning and stimulation. Because it is adjustable and reversible, deep brain stimulations (DBS) is preferable to ablative procedures. Traditionally, frame- based stereotaxy has been used to register these patients during deep electrode implantation. This study investigated the accuracy of the less invasive frameless registration method in 9 patients and found an overall mean error of 1.9mm (range: 1.1mm min, 2.7mm max) with an overall SD of 0.7mm. This error range is not acceptable for the submillimeter precision needed in microelectrode implantation. The lab is currently investing the accuracy of the frameless bone-screw marker method that is still less invasive and cumbersome than the frame-based system.

  15. Network effects of deep brain stimulation

    PubMed Central

    Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

    2015-01-01

    The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

  16. Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

    PubMed

    Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

    2017-03-01

    Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

  17. Cognitive Functioning in Children with Pantothenate-Kinase-Associated Neurodegeneration Undergoing Deep Brain Stimulation

    ERIC Educational Resources Information Center

    Mahoney, Rachel; Selway, Richard; Lin, Jean-Pierre

    2011-01-01

    Aim: To examine the cognitive functioning of young people with pantothenate-kinase-associated neurodegeneration (PKAN) after pallidal deep brain stimulation (DBS). PKAN is characterized by progressive generalized dystonia and has historically been associated with cognitive decline. With growing evidence that DBS can improve motor function in…

  18. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    ERIC Educational Resources Information Center

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  19. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    PubMed

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  20. A Bayesian statistical analysis of behavioral facilitation associated with deep brain stimulation

    PubMed Central

    Smith, Anne C; Shah, Sudhin A; Hudson, Andrew E; Purpura, Keith P; Victor, Jonathan D; Brown, Emery N; Schiff, Nicholas D

    2009-01-01

    Deep brain stimulation (DBS) is an established therapy for Parkinson’s Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large. We demonstrate how Bayesian state-space methods can be used to characterize the relationship between DBS and behavior comparing our approach with logistic regression in two experiments: the effects of DBS on attention of a macaque monkey performing a reaction-time task, and the effects of DBS on motor behavior of a human patient in a minimally conscious state. The state-space analysis can assess the magnitude of DBS behavioral facilitation (positive or negative) at specific time points and has important implications for developing principled strategies to optimize DBS paradigms. PMID:19576932

  1. Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging

    PubMed Central

    Hamani, Clement; Lozano, Andres M.; Mazzone, Paolo A.M.; Moro, Elena; Hutchison, William; Silburn, Peter A.; Zrinzo, Ludvic; Alam, Mesbah; Goetz, Laurent; Pereira, Erlick; Rughani, Anand; Thevathasan, Wesley; Aziz, Tipu; Bloem, Bastiaan R.; Brown, Peter; Chabardes, Stephan; Coyne, Terry; Foote, Kelly; Garcia-Rill, Edgar; Hirsch, Etienne C.; Okun, Michael S.; Krauss, Joachim K.

    2017-01-01

    The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss short-comings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS. PMID:27728909

  2. Ethical brain stimulation - neuroethics of deep brain stimulation in research and clinical practice.

    PubMed

    Clausen, Jens

    2010-10-01

    Deep brain stimulation (DBS) is a clinically established procedure for treating severe motor symptoms in patients suffering from end-stage Parkinson's disease, dystonia and essential tremor. Currently, it is tested for further indications including psychiatric disorders like major depression and a variety of other diseases. However, ethical issues of DBS demand continuing discussion. Analysing neuroethical and clinical literature, five major topics concerning the ethics of DBS in clinical practice were identified: thorough examination and weighing of risks and benefits; selecting patients fairly; protecting the health of children in paediatric DBS; special issues concerning patients' autonomy; and the normative impact of quality of life measurements. In exploring DBS for further applications, additionally, issues of research ethics have to be considered. Of special importance in this context are questions such as what additional value is generated by the research, how to realise scientific validity, which patients should be included, and how to achieve an acceptable risk-benefit ratio. Patients' benefit is central for ethical evaluation. This criterion can outweigh very serious side-effects, and can make DBS appropriate even in paediatrics. Because standard test procedures evade central aspects of patients' benefits, measuring quality of life should be supplemented by open in-depth interviews to provide a more adequate picture of patients' post-surgical situation. To examine its entire therapeutic potential, further research in DBS is needed. Studies should be based on solid scientific hypotheses and proceed cautiously to benefit severely suffering patients without putting them to undue risks.

  3. Tremor reduction by subthalamic nucleus stimulation and medication in advanced Parkinson's disease.

    PubMed

    Blahak, Christian; Wöhrle, Johannes C; Capelle, Hans-Holger; Bäzner, Hansjörg; Grips, Eva; Weigel, Ralf; Hennerici, Michael G; Krauss, Joachim K

    2007-02-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson's disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission.

  4. Direct electrical stimulation of the somatosensory cortex in humans using electrocorticography electrodes: a qualitative and quantitative report

    NASA Astrophysics Data System (ADS)

    Johnson, L. A.; Wander, J. D.; Sarma, D.; Su, D. K.; Fetz, E. E.; Ojemann, J. G.

    2013-06-01

    Objective. Recently, electrocorticography-based brain-computer interfaces have been successfully used to translate cortical activity into control signals for external devices. However, the utility of such devices would be greatly enhanced by somatosensory feedback. Direct stimulation of somatosensory cortex evokes sensory perceptions, and is thus a promising option for closing the loop. Before this can be implemented in humans it is necessary to evaluate how changes in stimulus parameters are perceived and the extent to which they can be discriminated. Approach. Electrical stimulation was delivered to the somatosensory cortex of human subjects implanted with electrocorticography grids. Subjects were asked to discriminate between stimuli of different frequency and amplitude as well as to report the qualitative sensations elicited by the stimulation. Main results. In this study we show that in humans implanted with electrocorticography grids, variations in the amplitude or frequency of cortical electrical stimulation produce graded variations in percepts. Subjects were able to reliably distinguish between different stimuli. Significance. These results indicate that direct cortical stimulation is a feasible option for sensory feedback with brain-computer interface devices.

  5. Uncovering the mechanism(s) of deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  6. Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions.

    PubMed

    Hescham, Sarah; Jahanshahi, Ali; Meriaux, Céline; Lim, Lee Wei; Blokland, Arjan; Temel, Yasin

    2015-10-01

    Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex.

  7. Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology

    PubMed Central

    Hamani, Clement; Aziz, Tipu; Bloem, Bastiaan R.; Brown, Peter; Chabardes, Stephan; Coyne, Terry; Foote, Kelly; Garcia-Rill, Edgar; Hirsch, Etienne C.; Lozano, Andres M.; Mazzone, Paolo A.M.; Okun, Michael S.; Hutchison, William; Silburn, Peter; Zrinzo, Ludvic; Alam, Mesbah; Goetz, Laurent; Pereira, Erlick; Rughani, Anand; Thevathasan, Wesley; Moro, Elena; Krauss, Joachim K.

    2017-01-01

    Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues. PMID:27723662

  8. The enhancement of neuronal cells wound healing with non-contact electric field stimulation by graphene electrodes

    NASA Astrophysics Data System (ADS)

    Lee, Sohee; Heo, Chaejeong; Lee, Si Young; Lee, Young Hee; Suh, Minah

    2013-05-01

    Electrical stimulation affects cellular behaviors including division, migration and wound healing [1-3]. Cellular injury often occurs due to the imbalance of the endogenous electric field [3]. In order to recover from the injury, wound healing process requires various cellular changes such as regeneration, migration, and the enhancement of cytoskeletal proteins and growth factors. In previous reports, a weak non-contact electric field stimulation (nEFS) accelerates the cell migration as well as cell-to-cell coupling between neuronal cell junction which are accompanied by increasing of cytoskeletal proteins [4, 5]. In this paper, we further investigated the wound healing effect of the nEFS in the neuronal cells (SHSY5Y cells) with live cell optical imaging. Cells were cultured over the optically transparent graphenen EF stimulator. Cellular behavioral changes upon nEFS were recorded with live optical imaging during stimulation of 120 minutes. The ability of wound healing was significantly enhanced with the nEFS. In particular, nEFS significantly shorten the duration of wound healing process. Moreover, after treating cells with cytochalasin D, a block polymerization of the actin filaments, the nEFS significantly enhanced wound healing process of cytochalasin D treated neural cells as compared to the control neural cells. This study suggests that nEFS may provide an effective way to control neural cells repairing process from cellular injury. Further mechanism study about the effect of nEFS on the wound healing may shed new light on cellular behavior.

  9. External trial deep brain stimulation device for the application of desynchronizing stimulation techniques

    NASA Astrophysics Data System (ADS)

    Hauptmann, C.; Roulet, J.-C.; Niederhauser, J. J.; Döll, W.; Kirlangic, M. E.; Lysyansky, B.; Krachkovskyi, V.; Bhatti, M. A.; Barnikol, U. B.; Sasse, L.; Bührle, C. P.; Speckmann, E.-J.; Götz, M.; Sturm, V.; Freund, H.-J.; Schnell, U.; Tass, P. A.

    2009-12-01

    In the past decade deep brain stimulation (DBS)—the application of electrical stimulation to specific target structures via implanted depth electrodes—has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

  10. Movement-related modulation of neural activity in human basal ganglia and its L-DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease.

    PubMed

    Priori, A; Foffani, G; Pesenti, A; Bianchi, A; Chiesa, V; Baselli, G; Caputo, E; Tamma, F; Rampini, P; Egidi, M; Locatelli, M; Barbieri, S; Scarlato, G

    2002-09-01

    Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinson's disease, we recorded the electrical activity from the human basal ganglia before, during and after voluntary contralateral finger movements, before and after L-DOPA. We analysed the movement-related spectral changes in the electroencephalographic signal from the subthalamic nucleus (STN) and from the internal globus pallidus (GPi). Before, during and after voluntary movements, signals arising from the human basal ganglia contained two main frequencies: a high beta (around 26 Hz), and a low beta (around 18 Hz). The high beta (around 26 Hz) power decreased in the STN and GPi, whereas the low beta (around 18 Hz) power decrease was consistently found only in the GPi. Both frequencies changed their power with a specific temporal modulation related to the different movement phases. L-DOPA specifically and selectively influenced the spectral power changes in these two signal bands.

  11. Deep brain stimulation in the globus pallidus externa promotes sleep.

    PubMed

    Qiu, M H; Chen, M C; Wu, J; Nelson, D; Lu, J

    2016-05-13

    The basal ganglia, a network of subcortical structures, play a critical role in movements, sleep and mental behavior. Basal ganglia disorders such as Parkinson's disease and Huntington's disease affect sleep. Deep brain stimulation (DBS) to treat motor symptoms in Parkinson's disease can ameliorate sleep disturbances. Our series of previous studies lead the hypothesis that dopamine, acting on D2 receptors on the striatopallidal terminals, enhances activity in the globus pallidus externa (GPe) and promotes sleep. Here, we tested if DBS in the GPe promotes sleep in rats. We found that unilateral DBS (180 Hz at 100 μA) in the GPe in rats significantly increased both non-rapid eye movement and rapid eye movement sleep compared to sham DBS stimulation. The EEG power spectrum of sleep induced by DBS was similar to that of the baseline sleep, and sleep latency was not affected by DBS. The GPe is potentially a better site for DBS to treat both insomnia and motor disorders caused by basal ganglia dysfunction.

  12. Micromachined electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.

    2007-12-11

    An electrode array is disclosed which has applications for neural stimulation and sensing. The electrode array, in certain embodiments, can include a plurality of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. In other embodiments of the electrode array, the electrodes can be fixed to the substrate. The electrode array can be formed from a combination of bulk and surface micromachining, and can include electrode tips having an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis.

  13. Flexible retinal electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.; Christenson, Todd R.

    2006-10-24

    An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

  14. A randomized double-blind crossover trial of deep brain stimulation of the subcallosal cingulate gyrus in patients with treatment-resistant depression: a pilot study of relapse prevention

    PubMed Central

    Puigdemont, Dolors; Portella, Maria J.; Pérez-Egea, Rosario; Molet, Joan; Gironell, Alexandre; de Diego-Adeliño, Javier; Martín, Anna; Rodríguez, Rodrigo; Àlvarez, Enric; Artigas, Francesc; Pérez, Víctor

    2015-01-01

    Background To date, antidepressant drugs show limited efficacy, leaving a large number of patients experiencing severe and persistent symptoms of major depression. Previous open-label clinical trials have reported significant sustained improvements with deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) in patients with severe, chronic treatment-resistant depression (TRD). This study aimed to confirm the efficacy and measure the impact of discontinuation of the electrical stimulation. Methods We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON–OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF–ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months. The primary outcome measure was the difference in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score between sham and active stimulation. Results We enrolled 5 patients in our trial. A Friedman repeated-measures analysis of variance revealed a significant effect of treatment (χ21 = 5.0, p = 0.025) in patients with higher depression scores during sham stimulation. At the end of active stimulation, depression was remitted in 4 of 5 patients and none of them had experienced a relapse, whereas at the end of sham stimulation, 2 patients remained in remission, 2 relapsed and 1 showed a progressive worsening without reaching relapse criteria. Limitations The small sample size limited the statistical power and external validity. Conclusion These preliminary findings indicate that DBS of the SCG is an effective and safe treatment for severe forms of TRD and that continuous electrical stimulation is required to maintain therapeutic effects

  15. Analysis of benzodiazepines and their metabolites using DBS cards and LC-MS/MS.

    PubMed

    Lee, Heesang; Park, Yujin; Jo, Jiyeong; In, Sangwhan; Park, Yonghoon; Kim, Eunmi; Pyo, Jaesung; Choe, Sanggil

    2015-10-01

    Dried Blood Spot (DBS) has been used a blood extraction method for inherited metabolic disorder screening since 1960s. With introduction of LC-MS/MS, not only DBS could be used to analysis drugs in small blood volume, but in various fields, such as toxicology, drug therapeutic monitoring, drug diagnostic screening, and illicit drugs. In toxicology field, many drugs (e.g. benzodiazepines, acetaminophen, small molecule drugs) have been tested with DBS. Compared with earlier blood extraction methods (SPE and LLE), DBS has lots of advantages; lower blood volume (less than 50μL), shorter analysis time caused by a more concise analysis procedure and lower cost. We optimized the DBS procedure and LC-MS/MS conditions for 18 benzodiazepines, seven benzodiazepine metabolites, and one z-drug (zolpidem) analysis in blood. 30μL of whole blood was spotted on FTA DMPK card C and dried for 2h in a desiccator. A 6-mm disk was punched and vortexed for 1min in a centrifuge tube with 300μL methanol/acetonitrile mixture (1:1, v/v). After evaporation, redissolved in 100μL mobile phase of LC-MS/MS and 5μL was injected. In the analysis for 26 target compounds in blood, all of the method validation parameters - LLOD, LLOQ, accuracy (intra- and inter-assay), and precision (intra- and inter-assay) - were satisfied with method validation criteria, within 15%. The results of matrix effect, recovery, and process efficiency were good. We developed a fast and reliable sample preparation method using DBS for 26 benzodiazepines, benzodiazepine metabolites, and z-drug (zolpidem).

  16. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats.

    PubMed

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G P; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J; la Fleur, Susanne E

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients.

  17. Current Steering to Control the Volume of Tissue Activated During Deep Brain Stimulation

    PubMed Central

    Butson, Christopher R.; McIntyre, Cameron C.

    2009-01-01

    Background Over the last two decades, deep brain stimulation (DBS) has become a recognized and effective clinical therapy for numerous neurological conditions. Since its inception, clinical DBS technology has progressed at a relatively slow rate; however, advances in neural engineering research have the potential to improve DBS systems. One such advance is the concept of current steering, or the use of multiple stimulation sources to direct current flow through targeted regions of brain tissue. Objective The goals of this study were to develop a theoretical understanding of the effects of current steering in the context of DBS, and use that information to evaluate the potential utility of current steering during stimulation of the subthalamic nucleus. Methods We used finite element electric field models, coupled to multi-compartment cable axon models, to predict the volume of tissue activated (VTA) by DBS as a function of the stimulation parameter settings. Results Balancing current flow through adjacent cathodes increased the VTA magnitude, relative to monopolar stimulation, and current steering enabled us to sculpt the shape of the VTA to fit a given anatomical target. Conclusions These results provide motivation for the integration of current steering technology into clinical DBS systems, thereby expanding opportunities to customize DBS to individual patients, and potentially enhancing therapeutic efficacy. PMID:19142235

  18. Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

    PubMed Central

    Rossi, P. Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J.; Elias, W. Jeff; Rossi, Marvin A.; Butson, Christopher L.; Fox, Michael D.; McIntyre, Cameron C.; Pouratian, Nader; Swann, Nicole C.; de Hemptinne, Coralie; Gross, Robert E.; Chizeck, Howard J.; Tagliati, Michele; Lozano, Andres M.; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L.; Akbar, Umer; Gerhardt, Greg A.; Grill, Warren M.; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H.; Lang, Anthony E.; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y.; Molina, Rene; Opri, Enrico; Otto, Kevin J.; Oweiss, Karim G.; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A.; Shih, Ludy C.; Steinke, G. Karl; Tröster, Alexander I.; Vanegas, Nora; Zaghloul, Kareem A.; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D.; Okun, Michael S.

    2016-01-01

    The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies. PMID:27092042

  19. Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

    PubMed

    Rossi, P Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J; Elias, W Jeff; Rossi, Marvin A; Butson, Christopher L; Fox, Michael D; McIntyre, Cameron C; Pouratian, Nader; Swann, Nicole C; de Hemptinne, Coralie; Gross, Robert E; Chizeck, Howard J; Tagliati, Michele; Lozano, Andres M; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L; Akbar, Umer; Gerhardt, Greg A; Grill, Warren M; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H; Lang, Anthony E; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y; Molina, Rene; Opri, Enrico; Otto, Kevin J; Oweiss, Karim G; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A; Shih, Ludy C; Steinke, G Karl; Tröster, Alexander I; Vanegas, Nora; Zaghloul, Kareem A; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D; Okun, Michael S

    2016-01-01

    The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

  20. Subthalamic Nucleus Stimulation Modulates Thalamic Neuronal Activity

    PubMed Central

    Xu, Weidong; Russo, Gary S.; Hashimoto, Takao; Zhang, Jianyu; Vitek, Jerrold L.

    2009-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is an effective tool for the treatment of advanced Parkinson’s disease. The mechanism by which STN DBS elicits its beneficial effect, however, remains unclear. We previously reported STN stimulation increased the rate and produced a more regular and periodic pattern of neuronal activity in the internal segment of the globus pallidus (GPi). Here we extend our observations to neurons in the pallidal (ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)) and cerebellar (ventralis lateralis posterior pars oralis (VPLo)) receiving areas of the motor thalamus during STN DBS. Stimulation parameters that produced improvement in rigidity and bradykinesia resulted in changes in the pattern and power of oscillatory activity of neuronal activity that were similar in both regions of the motor thalamus. Neurons in both VA/VLo and VPLo tended to become more periodic and regular with a shift in oscillatory activity from low to high frequencies. Burst activity was reduced in VA/VLo, but was not significantly changed in VPLo. There was also a significant shift in the population of VA/VLo neurons that were inhibited during STN DBS, while VPLo neurons tended to be activated. These data are consistent with the hypothesis that STN DBS increases output from the nucleus and produces a change in the pattern and periodicity of neuronal activity in the basal ganglia thalamic network, and that these changes include cerebellar pathways likely via activation of adjacent cerebello-thalamic fiber bundles. PMID:19005057

  1. Perceived articulatory precision in patients with Parkinson's disease after deep brain stimulation of subthalamic nucleus and caudal zona incerta.

    PubMed

    Eklund, Elisabeth; Qvist, Johanna; Sandström, Lena; Viklund, Fanny; Van Doorn, Jan; Karlsson, Fredrik<