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Sample records for stimulation dbs electrodes

  1. Lead-DBS: a toolbox for deep brain stimulation electrode localizations and visualizations.

    PubMed

    Horn, Andreas; Khn, Andrea A

    2015-02-15

    To determine placement of electrodes after deep brain stimulation (DBS) surgery, a novel toolbox that facilitates both reconstruction of the lead electrode trajectory and the contact placement is introduced. Using the toolbox, electrode placement can be reconstructed and visualized based on the electrode-induced artifacts on post-operative magnetic resonance (MR) or computed tomography (CT) images. Correct electrode placement is essential for efficacious treatment with DBS. Post-operative knowledge about the placement of DBS electrode contacts and trajectories is a promising tool for clinical evaluation of DBS effects and adverse effects. It may help clinicians in identifying the best stimulation contacts based on anatomical target areas and may even shorten test stimulation protocols in the future. Fifty patients that underwent DBS surgery were analyzed in this study. After normalizing the post-operative MR/CT volumes into standard Montreal Neurological Institute (MNI)-stereotactic space, electrode leads (n=104) were detected by a novel algorithm that iteratively thresholds each axial slice and isolates the centroids of the electrode artifacts within the MR/CT-images (MR only n=32, CT only n=10, MR and CT n=8). Two patients received four, the others received two quadripolar DBS leads bilaterally, summing up to a total of 120 lead localizations. In a second reconstruction step, electrode contacts along the lead trajectories were reconstructed by using templates of electrode tips that had been manually created beforehand. Reconstructions that were made by the algorithm were finally compared to manual surveys of contact localizations. The algorithm was able to robustly accomplish lead reconstructions in an automated manner in 98% of electrodes and contact reconstructions in 69% of electrodes. Using additional subsequent manual refinement of the reconstructed contact positions, 118 of 120 electrode lead and contact reconstructions could be localized using the toolbox. Taken together, the toolbox presented here allows for a precise and fast reconstruction of DBS contacts by proposing a semi-automated procedure. Reconstruction results can be directly exported to two- and three-dimensional views that show the relationship between DBS contacts and anatomical target regions. The toolbox is made available to the public in form of an open-source MATLAB repository. PMID:25498389

  2. Subacute Subdural Hematoma in a Patient with Bilateral DBS Electrodes

    PubMed Central

    Nguyen, Ha Son; Pahapill, Peter A.

    2015-01-01

    Subdural hematomas (SDH) in patients with implanted deep brain stimulating (DBS) electrodes are rare. Only a handful of cases have been reported in the literature. No clear management guidelines exist regarding the management of the hematoma and the existing electrodes. We describe a 68-year-old female with bilateral DBS electrodes, who presented with acute, severe hemiparesis due to a large subacute SDH with associated electrode displacement. Urgent hematoma evacuation reversed the hemiparesis; the electrodes were left undisturbed. Brain reexpansion occurred promptly. The patient was able to benefit from stable DBS therapies within 3 weeks of hematoma evacuation, maintained at 1.5-year follow-up. The case highlights that despite relative electrode migration due to a subdural hematoma, the electrodes may not require revision during initial hematoma evacuation or in a delayed fashion. Timely hematoma evacuation, coupled with brain reexpansion, may be adequate for the electrode to travel back to its original position and effect reasonable DBS therapies. PMID:26779357

  3. The ethics of deep brain stimulation (DBS).

    PubMed

    Unterrainer, Marcus; Oduncu, Fuat S

    2015-11-01

    Deep brain stimulation (DBS) is an invasive technique designed to stimulate certain deep brain regions for therapeutic purposes and is currently used mainly in patients with neurodegenerative disorders, such as Parkinson's disease. However, DBS is also used increasingly for other experimental applications, such as the treatment of psychiatric disorders (e.g. severe depression), weight reduction. Apart from its therapeutic potential, DBS can cause severe adverse effects, some that might also have a significant impact on the patient's personality and autonomy by the external stimulation of DBS which effects lie beyond the individual's control and free will. The article's purpose is to outline the procedures of DBS currently used in therapeutic and experimental applications and to discuss the ethical concerns regarding this procedure. It will address the clinical benefit-risk-ratio, the particular ethics of research in this field, and the ethical issues raised by affecting a patient's or an individual's personality and autonomous behaviour. Moreover, a potential ethical guideline, the Ulysses contract is discussed for the field of clinical application as well as the question of responsibility. PMID:25597042

  4. 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

  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. PMID:22764359

  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. [Trajectory of a patient with deep brain stimulation (DBS)].

    PubMed

    Horvath, Judit; Chiuv, Sabina Catalano; Gronchi-Perrin, Aline; Zacharia, Andr; Wider, Christian; Fleury, Vanessa

    2015-04-29

    An eligibility assessment for deep brain stimulation is performed in order to select patients who are likely to benefit from it. Parkinson's patients have to stop dopaminergic drugs the day before surgery. During the operation, the patient must remain awake for recording of neuronal activity and for test stimulations to optimize the position of the electrodes. Postoperatively, the stimulation is increased progressively in parallel with a decrease of dopaminergic treatments. After about ten days, the patient can return to home and controls continue as an outpatient. Three months postoperatively, a complete testing of the neurostimulator is performed and at the one year follow-up visit, the effectiveness of the DBS is assessed. PMID:26062222

  8. 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. Hum Brain Mapp 37:422-433, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID:26523416

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

    PubMed Central

    Ineichen, Christian; Glannon, Walter; Temel, Yasin; Baumann, Christian R.; Src, 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, IPGs) 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

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

    PubMed

    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

  11. Deep brain stimulation (DBS) attentional effects parallel those of l-dopa treatment.

    PubMed

    Brusa, L; Pierantozzi, M; Peppe, A; Altibrandi, M G; Giacomini, P; Mazzone, P; Stanzione, P

    2001-01-01

    Aim of our study was to investigate the different effects on attentional capacity of deep brain stimulation DBS (STN or GPi) and of l-dopa in PD patients. Patients were evaluated on-DBS/off-l-dopa, on-l-dopa/off-DBS, on-l-dopa/on-DBS and off-l-dopa/off-DBS. Our results indicate that DBS effects on attentional functions parallel those of l-dopa. A site independent (both STN and GPi) worsening of verbal fluency was observed, possibly connected to the stimulus effect on the cortico-subcortical-cortical loop. PMID:11716137

  12. 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

  13. In vivo impedance spectroscopy of deep brain stimulation electrodes

    NASA Astrophysics Data System (ADS)

    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.

  14. Long-Term Migration of a Deep Brain Stimulation (DBS) Lead in the Third Ventricle Caused by Cerebral Atrophy in a Patient with Anterior Thalamic Nucleus DBS

    PubMed Central

    Choi, Jin-gyu; Lee, Si-hoon; Shon, Young-Min; Son, Byung-chul

    2015-01-01

    The long-term (5-years) antiepileptic effect of deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) against refractory epilepsy has been reported. However, experience with ANT DBS for epilepsy is limited, and so hardware complications and technical problems related to ANT DBS are unclear. We report the case of a 57-year-old male who underwent re-implantation of a DBS lead in the left ANT because of lead migration into the third ventricle detected 8 years after the first DBS, and which was caused by the significant enlargement of the lateral and third ventricles. After re-implantation, the patient showed a mechanically-related antiepileptic effect and a prominent driving response of the electroencephalography was verified. We speculate that progressive dilatation of the ventricle and shallow, insufficient implantation of the lead during the initial ANT DBS may have caused migration of the DBS lead. Because dilatation of the ventricle could progress years after DBS in a patient with chronic epilepsy, regular follow-up imaging is warranted in ANT DBS patients with an injured, atrophied brain. PMID:26819942

  15. Long-Term management of DBS in dystonia: response to stimulation, adverse events, battery changes, and special considerations.

    PubMed

    Tagliati, Michele; Krack, Paul; Volkmann, Jens; Aziz, Tipu; Krauss, Joachim K; Kupsch, Andreas; Vidailhet, And Marie

    2011-06-01

    Multiple independent case series have documented sustained benefit of bilateral pallidal deep brain stimulation (DBS) up to 3 years in patients with primary dystonia. Growing evidence exists for positive outcomes extending up to 10 years. The beneficial effects from DBS are usually reported to be stable, thus requiring little long-term modifications of the parameters of stimulation. Speech and swallowing abnormalities are less responsive than other dystonic symptoms. Symptom exacerbation after initial benefit has been reported in a few cases. It is not known whether this is related to potential tolerance or habituation to stimulation or to progression of the underlying disease. Failures of pallidal DBS, at least in primary dystonia patients, should not be accepted without further re-evaluation of each individual case, including possible revisions of the electrode location. Both hardware- and stimulation-related adverse effects, including insufficient relief of speech function, have been reported in the long-term. Despite early reports suggesting that hardware problems might be more frequent in dystonia, more recent studies did not confirm these observations. In patients with severe segmental (e.g., axial) or generalized dystonia, sudden cessation of stimulation may become a medical emergency and should be anticipated changing the neurostimulator before its natural end of life. PMID:21692113

  16. 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 casestissue anisotropy, a long active electrode and bipolar stimulationwas also examined. Under the conditions considered, the point source was shown to be a valid approximation for predicting excitation of populations of neurons in response to DBS.

  17. The VU-DBS project: integrated and computer-assisted planning, intra-operative placement, and post-operative programming of deep-brain stimulators

    NASA Astrophysics Data System (ADS)

    Dawant, Benoit M.; D'Haese, Pierre-Francois; Pallavaram, Srivatsan; Li, Rui; Yu, Hong; Spooner, John; Davis, Thomas; Kao, Chris; Konrad, Peter E.

    2007-03-01

    Movement disorders affect over 5,000,000 people in the United States. Contemporary treatment of these diseases involves high-frequency stimulation through deep brain stimulation (DBS). This form of therapy is offered to patients who have begun to see failure with standard medical therapy and also to patients for which medical therapy is poorly effective. A DBS procedure involves the surgical placement, with millimetric accuracy, of an electrode in the proximity of functional areas referred to as targets. Following the surgical procedure, the implant, which is a multi-contact electrode is programmed to alleviate symptoms while minimizing side effects. Surgical placement of the electrode is difficult because targets of interest are poorly visible in current imaging modalities. Consequently, the process of implantation of a DBS electrode is an iterative procedure. An approximate target position is determined pre-operatively from the position of adjacent structures that are visible in MR images. With the patient awake, this position is then adjusted intra-operatively, which is a lengthy process. The post-surgical programming of the stimulator is an equally challenging and time consuming task, with parameter setting combinations exceeding 4000. This paper reports on the status of the Vanderbilt University DBS Project, which involves the development and clinical evaluation of a system designed to facilitate the entire process from the time of planning to the time of programming.

  18. 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

  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. 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. PMID:26779322

  1. Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals

    PubMed Central

    Min, Hoon-Ki; Hwang, Sun-Chul; Marsh, Michael P.; Kim, Inyong; Knight, Emily; Striemer, Bryan; Felmlee, Joel P.; Welker, Kirk M.; Blaha, Charles D.; Chang, Su-Youne; Bennet, Kevin E.; Lee, Kendall H.

    2012-01-01

    The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. The goal of this study was to trace DBS-induced global neuronal network activation in a large animal model by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus (STN) (n=7) and the entopeduncular nucleus (EN), the non-primate analogue of the primate globus pallidus interna (n=4). Using a normalized functional activation map for group analysis and the application of general linear modeling across subjects, we found that both STN and EN DBS significantly increased BOLD activation in the ipsilateral sensorimotor network (FDR < 0.001). In addition, we found differential, target-specific, non-motor network effects. In each group the activated brain areas showed a distinctive correlation pattern forming a group of network connections. Results suggest that the scope of DBS extends beyond an ablation-like effect and that it may have modulatory effects not only on circuits that facilitate motor function but also on those involved in higher cognitive and emotional processing. Taken together, our results show that the swine model for DBS fMRI, which conforms to human implanted DBS electrode configurations and human neuroanatomy, may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS. PMID:22967832

  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. PMID:21859605

  4. Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD

    PubMed Central

    Vigil, Julie; MacCracken, Ellen; Gasparaitis, Arunas; Young, Joan; Kang, Wenjun; Bernard, Jacqueline; Warnke, Peter; Kang, Un J.

    2015-01-01

    Objectives: To study whether 60-Hz stimulation, compared with routine 130 Hz, improves swallowing function and freezing of gait (FOG) in patients with Parkinson disease (PD) who undergo bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: We studied 7 patients with PD who experienced FOG that persisted despite routine 130-Hz stimulation and dopaminergic medication. Each patient received 3 modified barium swallow (MBS) studies in a single day under 3 DBS conditions in the medication-on state: 130 Hz, 60 Hz, or DBS off, in a randomized double-blind manner. The laryngeal penetration and aspiration events were cautiously assessed, and a swallowing questionnaire was completed. The Unified Parkinson's Disease Rating Scale, Part III motor score, axial subscore, tremor subscore, and FOG by a questionnaire and stand-walk-sit test were also assessed. The best DBS condition (60 Hz here) producing the least FOG was maintained for 3 to 8 weeks, and patients were assessed again. Changes in measurements between the 60 Hz and 130 Hz were analyzed using paired t test, with swallowing function as primary and the remainder as secondary outcomes. Changes between other DBS conditions were further explored with Bonferroni correction. Results: Compared with the routine 130 Hz, 60-Hz stimulation significantly reduced aspiration frequency by 57% on MBS study and perceived swallowing difficulty by 80% on questionnaire. It also significantly reduced FOG, and axial and parkinsonian symptoms. The benefits at 60-Hz stimulation persisted over the average 6-week assessment. Conclusions: Compared with the routine 130 Hz, the 60-Hz stimulation significantly improved swallowing function, FOG, and axial and parkinsonian symptoms in patients with PD treated with bilateral STN-DBS, which persisted over the 6-week study period. Classification of evidence: This study provides Class IV evidence that for patients with PD who experience FOG, STN-DBS at 60 Hz decreases aspiration events observed during MBS compared with DBS at 130 Hz. PMID:25540305

  5. Influences of interpolation error, electrode geometry, and the electrode-tissue interface on models of electric fields produced by deep brain stimulation.

    PubMed

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

    2014-02-01

    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

  6. CranialVault and its CRAVE tools: a clinical computer assistance system for Deep Brain Stimulation (DBS) therapy

    PubMed Central

    D’Haese, Pierre-François; Pallavaram, Srivatsan; Li, Rui; Remple, Michael S.; Kao, Chris; Neimat, Joseph S.; Konrad, Peter E.; Dawant, Benoit M.

    2010-01-01

    A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAVE (CRAnialVault Explorer) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information. PMID:20732828

  7. Electrode displacement after intracerebral hematoma as a complication of a deep brain stimulation procedure

    PubMed Central

    Servello, Domenico; Sassi, Marco; Bastianello, Stefano; Poloni, Guy Umberto; Mancini, Francesca; Pacchetti, Claudio

    2009-01-01

    Objectives: Deep brain stimulation (DBS) is nowadays considered a safe and effective procedure for various movement disorders in which conservative treatments have failed to show significant therapeutic results. One of the most common complications of definitive electrode positioning is intraparenchymal hemorrhage. Materials and methods: Authors report the case of a 55-year-old female patient treated for Parkinsons disease in which intraparenchymal hemorrhage developed after DBS procedure, leading to significant (about 8 mm at the neuroradiological controls) displacement of an otherwise correctly positioned DBS electrode. Results: After conservative management, the hematoma spontaneously resolved. Late neuroradiological controls documented correct, symmetrically positioned electrodes, comparable to the immediate postoperative controls. Conclusions: Six months follow-up endpoint results of the DBS treatment were considered satisfying by an independent neurologist, with modest residual neurological deficits, demonstrating that re-positioning of the electrode was unnecessary in this rare complication. PMID:19557113

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

    PubMed

    Xiao, YiZi; Pena, Edgar; Johnson, Matthew D

    2016-02-01

    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. 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. 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. 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. The algorithm provides an efficient, flexible determination of optimal electrode configurations for programming DBS arrays. PMID:26208259

  9. Standard Guidelines for Publication of Deep Brain Stimulation Studies in Parkinsons 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 Parkinsons 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

  10. Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation.

    PubMed

    Fluri, Felix; Bieber, Micheal; Volkmann, Jens; Kleinschnitz, Christoph

    2015-01-01

    Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson's disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 M? was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength. PMID:26485522

  11. Electrode array for neural stimulation

    SciTech Connect

    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.

  12. 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.

  13. Evaluation of High-Perimeter Electrode Designs for Deep Brain Stimulation

    PubMed Central

    Howell, Bryan; Grill, Warren M.

    2014-01-01

    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 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 perimeter or area had a greater effect on increasing stimulation efficiency. 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. The results indicated that: (1) area had a greater effect than perimeter on altering the electrode access resistance; (2) 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 (3) quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes. PMID:25029124

  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. Neural Stimulation via Fractal Electrodes

    NASA Astrophysics Data System (ADS)

    Montgomery, Rick; Watterson, William; Pilgrim, Ian; Fairley, Kurtis; Johnson, Darren; Linke, Heiner; Taylor, Richard

    2013-03-01

    A host of physical phenomena exhibit fractal geometry and benefit from its enhanced properties, which can include large surface area-to-volume ratios and high network connectivity. These properties are exploited in a fractal electrode designed for neural stimulation and recording. Presented are electric field studies of a fractal electrode with an emphasis on applications in retinal implants. Air Force Research Laboratory FA8650-05-1-5041

  16. Improvement of hand dexterity induced by stimulation of the peduncolopontine nucleus in a patient with advanced Parkinson's disease and previous long-lasting bilateral subthalamic DBS.

    PubMed

    Franzini, Angelo; Messina, Giuseppe; Zekaj, Edvin; Romito, Luigi; Cordella, Roberto

    2011-08-01

    We report the case of a patient already submitted to bilateral deep-brain stimulation (DBS) of the subthalamic nucleus (STN) who started to develop gait impairment, postural imbalance and frequent falls in the course of the disease and who subsequently underwent DBS of the right pedunculopontine nucleus (PPN) at our institute. An immediate clinical benefit in hand dexterity was observed with acute external stimulation and maintained after the definitive implant of the internal pulse generator (IPG) at 6 months' follow-up. The benefit on hand dexterity seemed to be related to the interactions between the PPN low-frequency stimulation and the bilateral STN high-frequency stimulation. PMID:21638144

  17. 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.

  18. Long-term effect on dystonia after pallidal deep brain stimulation (DBS) in three members of a family with a THAP1 mutation.

    PubMed

    Krause, P; Brggemann, N; Vlzmann, S; Horn, A; Kupsch, A; Schneider, G-H; Lohmann, K; Khn, A

    2015-12-01

    Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment in patients with severe dystonia. However, factors predicting outcome are largely unknown and motor improvement in DYT6 patients after DBS has been reported to be poorer as compared to, e.g., DYT1 patients. Here, we report the course of clinical improvement for up to 11years of pallidal DBS in three male patients belonging to the same family with early-onset generalized or segmental dystonia due to a heterozygous THAP1 gene mutation (DYT6). All patients showed an initial effective response to pallidal DBS with a mean of 56.911.7% improvement in the Burke-Fahn-Marsden Dystonia motor and 45.522.4% in the disability score at 1-year follow-up. The long-term outcome of pallidal DBS was favorable in two patients (39, 67% motor improvement, respectively). Our findings demonstrate that motor improvement is variable and may depend on disease severity, disease duration, and clinical presentation. Overall, our observation supports pallidal DBS as an important treatment option in patients with DYT6 dystonia. PMID:26486352

  19. 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 the original dimensions (1500 µm), with the opposite effect on the ECAP at longer contact-to-contact distances (2000 µm). Finally, acute edema reduced the single neuron and population ECAP signal energy, as well as LFP magnitude, and glial encapsulation had the opposite effect, after accounting for loss of cells in the peri-electrode space. Significance. This study determined recording conditions and electrode designs that influence ECAP and LFP recording fidelity.

  20. Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson disease

    PubMed Central

    Hill, K.K.; Campbell, M.C.; McNeely, M.E.; Karimi, M.; Ushe, M.; Tabbal, S.D.; Hershey, T.; Flores, H.P.; Hartlein, J.M.; Lugar, H.M.; Revilla, F.J.; Videen, T.O.; Earhart, G.M.; Perlmutter, J.S.

    2012-01-01

    Objectives The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS. Methods We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS. Results DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity related to premotor cortex rCBF changes during V-STN DBS (r = ?0.40, p = 0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r = ?0.43, p = 0.02). Conclusions DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location. PMID:23262122

  1. Dilemmas surrounding the diagnosis of deep brain stimulation electrode infection without associated wound complications: A series of two cases

    PubMed Central

    Nguyen, Ha Son; Doan, Ninh; Gelsomino, Michael; Shabani, Saman; Mueller, Wade

    2016-01-01

    Background: When wounds are benign, diagnosis of deep brain stimulation (DBS) electrode infection and associated intraparenchymal infection can be challenging. Only a couple, such cases exist in literature. Since infections of the central nervous system can be life-threatening, prompt diagnosis is necessary to prevent neurological injury. Employed within the appropriate context, magnetic resonance imaging (MRI) of the brain, as well as laboratory data and clinical presentation, may help guide diagnosis. Case Descriptions: Case 1 - A 55-year-old male with bilateral DBS electrodes and generators (49 days from last procedure), who presented with confusion and fever. Pertinent positive laboratory was white blood cell 20.5K. MRI of the brain showed edema with enhancement along the right DBS electrode. Wound exploration revealed gross purulence in the subgaleal space. The entire system was removed; cultures from subgaleal space revealed Propionibacterium acnes; cultures from electrode were negative. The patient was sent home on antibiotics. Case 2 - A 68-year-old male with a right DBS electrode (11 days from placement), who presented after an unwitnessed fall, followed by confusion and amnesia. Pertinent laboratory examinations were negative. MRI of the brain showed edema with enhancement along the DBS electrode. Wound exploration revealed no infection. The DBS system was left in place; final cultures were negative; no antibiotics were prescribed. Repeat MRI showed resolving fluid-attenuated inversion recovery (FLAIR) signal and contrast enhancement. Conclusions: Contrast enhancement, T2 FLAIR, and diffusion weighted imaging are influenced by postoperative changes. Caution is stressed regarding dependence on these features for acute diagnosis of infection and indication for electrode removal. Timing of the imaging after surgery must be considered. Other factors, such as systemic signs and abnormal laboratory data, should be evaluated. Based on these guidelines, retrospectively, the patient in Case 2 should not have been rushed for a wound exploration; close observation with serial imaging and laboratory data may have prevented an unnecessary procedure. PMID:26958428

  2. 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

  3. Mood response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

    PubMed

    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's disease (PD) improves motor functioning but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. The authors 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 and 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

  4. Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease.

    PubMed

    Cui, Zhiqiang; Pan, Longsheng; Song, Huifang; Xu, Xin; Xu, Bainan; Yu, Xinguang; Ling, Zhipei

    2016-01-01

    OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery. PMID:26274983

  5. 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

  6. New targets for DBS.

    PubMed

    Benabid, Alim Louis; Torres, Napoleon

    2012-01-01

    The specific effect of DBS at high frequency, discovered during a VIM thalamotomy, was extended to the older targets of ablative neurosurgery such as the pallidum, for tremor in Parkinson's disease (PD), dyskinesias, essential tremor, as well as the internal capsule to treat psychiatric disorders (OCD). A second wave of targets came from basic research, enabled by the low morbidity, reversibility, and adaptability of DBS. This was the case for the subthalamic nucleus (STN) which improves the triad of dopaminergic symptoms, and the pedunculopontine nucleus (PPN) for gait disorders in PD. The new concepts of the role of basal ganglia in psychiatric disorders indicate the subgenual cortex CG 25 for severe resistant depression, the accumbens nucleus for depression, anorexia nervosa, and addiction, and the thalamus intralaminar nuclei for minimally conscious states. Serendipity and a scientific approach have provided several instances where targets have produced unexpected effects (such as STN in OCD), as well as limbic effects observed during attempts at VMH stimulation for obesity: this might offer a novel way to treat mild cognitive impairment, or memory deficits reported in Alzheimer's disease. While these might provide solutions for as yet unsolved problems, attention must be paid to ethical considerations. PMID:22166437

  7. Numerical characterization of intraoperative and chronic electrodes in deep brain stimulation

    PubMed Central

    Paffi, Alessandra; Camera, Francesca; Apollonio, Francesca; dInzeo, Guglielmo; Liberti, Micaela

    2015-01-01

    An intraoperative electrode (microelectrode) is used in the deep brain stimulation (DBS) technique to pinpoint the brain target and to choose the best parameters for the electrical stimulus. However, when the intraoperative electrode is replaced with the chronic one (macroelectrode), the observed effects do not always coincide with predictions. To investigate the causes of such discrepancies, a 3D model of the basal ganglia has been considered and realistic models of both intraoperative and chronic electrodes have been developed and numerically solved. Results of simulations of the electric potential (V) and the activating function (AF) along neuronal fibers show that the different geometries and sizes of the two electrodes do not change the distributions and polarities of these functions, but rather the amplitudes. This effect is similar to the one produced by the presence of different tissue layers (edema or glial tissue) in the peri-electrode space. Conversely, an inaccurate positioning of the chronic electrode with respect to the intraoperative one (electric centers not coincident) may induce a completely different electric stimulation in some groups of fibers. PMID:25745397

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Three-dimensional localization of cortical electrodes in deep brain stimulation surgery from intraoperative fluoroscopy.

    PubMed

    Randazzo, Michael J; Kondylis, Efstathios D; Alhourani, Ahmad; Wozny, Thomas A; Lipski, Witold J; Crammond, Donald J; Richardson, R Mark

    2016-01-15

    Electrophysiological recordings from subdural electrocorticography (ECoG) electrodes implanted temporarily during deep brain stimulation (DBS) surgeries offer a unique opportunity to record cortical activity for research purposes. The optimal utilization of this important research method relies on accurate and robust localization of ECoG electrodes, and intraoperative fluoroscopy is often the only imaging modality available to visualize electrode locations. However, the localization of a three-dimensional electrode position using a two-dimensional fluoroscopic image is problematic due to the lost dimension orthogonal to the fluoroscopic image, a parallax distortion implicit to fluoroscopy, and variability of visible skull contour among fluoroscopic images. Here, we present a method to project electrodes visible on the fluoroscopic image onto a reconstructed cortical surface by leveraging numerous common landmarks to translate, rotate, and scale coregistered computed tomography (CT) and magnetic resonance imaging (MRI) reconstructed surfaces in order to recreate the coordinate framework in which the fluoroscopic image was acquired, while accounting for parallax distortion. Validation of this approach demonstrated high precision with an average total Euclidian distance between three independent reviewers of 1.65±0.68mm across 8 patients and 82 electrodes. Spatial accuracy was confirmed by correspondence between recorded neural activity over sensorimotor cortex during hand movement. This semi-automated interface reliably estimates the location of temporarily implanted subdural ECoG electrodes visible on intraoperative fluoroscopy to a cortical surface. PMID:26520771

  10. Neurophysiology of deep brain stimulation.

    PubMed

    Rosa, Manuela; Giannicola, Gaia; Marceglia, Sara; Fumagalli, Manuela; Barbieri, Sergio; Priori, Alberto

    2012-01-01

    We review the data concerning the neurophysiology of deep brain stimulation (DBS) in humans, especially in reference to Parkinson's disease. The electric field generated by DBS interacts with the brain in complex ways, and several variables could influence the DBS-induced biophysical and clinical effects. The neurophysiology of DBS comprises the DBS-induced effects per se as well as neurophysiological studies designed to record electrical activity directly from the basal ganglia (single-unit or local field potential) through the electrodes implanted for DBS. In the subthalamic nucleus, DBS locally excites and concurrently inhibits at single-unit level, synchronizes low-frequency activity, and desynchronizes beta activity and also induces neurochemical changes in cyclic guanosine monophosphate (cGMP) and GABA concentrations. DBS-induced effects at system level can be studied through evoked potentials, autonomic tests, spinal cord segmental system, motor cortical and brainstem excitability, gait, and decision-making tasks. All these variables are influenced by DBS, suggesting also distant effects on nonmotor structures of the brain. Last, advances in understanding the neurophysiological mechanisms underlying DBS led researchers to develop a new adaptive DBS technology designed to adapt stimulation settings to the individual patient's clinical condition through a closed-loop system controlled by signals from the basal ganglia. PMID:23206677

  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

    2015-01-01

    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

  12. 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

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

    PubMed

    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 ?s 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

  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 ?s 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. 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. PMID:22255884

  16. 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. PMID:23685268

  17. Electroconvulsive therapy in patients with deep brain stimulators.

    PubMed

    Vila-Rodriguez, Fidel; McGirr, Alex; Tham, Joseph; Hadjipavlou, George; Honey, Christopher R

    2014-09-01

    The scope of functional neurosurgery is expanding, and deep brain stimulation (DBS) indications with comorbid depressive disorders that are challenging to manage, such as movement disorders, are common. There is limited research or clinical experience on the safety and efficacy of electroconvulsive therapy (ECT) in patients with DBS electrodes. We present a case illustrating the challenges when faced with ECT for treatment-resistant depression in the context of preexisting DBS electrodes, and establish a database to collect cases of ECT in DBS patients. PMID:24625701

  18. Deep brain stimulation for refractory epilepsy

    PubMed Central

    Mandat, Tomasz; Kornakiewicz, Anna; Koziara, Henryk; Nauman, Pawe?

    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

  19. 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

  20. A Preliminary Report on Disordered Speech with Deep Brain Stimulation in Individuals with Parkinson's Disease

    PubMed Central

    Dromey, Christopher; Bjarnason, Suzy

    2011-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proven effective in treating the major motor symptoms of advanced Parkinson's disease (PD). The aim of this study was to learn which laryngeal and articulatory acoustic features changed in patients who were reported to have worse speech with stimulation. Six volunteers with PD who had bilateral STN electrodes were recorded with DBS turned on or off. Perceptual ratings reflected poorer speech performance with DBS on. Acoustic measures of articulation (corner vowel formants, diphthong slopes, and a spirantization index) and phonation (perturbation, long-term average spectrum) as well as verbal fluency scores showed mixed results with DBS. Some speakers improved while others became worse on individual measures. The magnitude of DBS effects was not predictable based on the patients' demographic characteristics. Future research involving adjustments to stimulator settings or electrode placement may be beneficial in limiting the negative effects of DBS on speech. PMID:22046577

  1. MRI-Related Heating near Deep Brain Stimulation Electrodes: More Data Are Needed

    PubMed Central

    Gupte, Akshay A.; Shrivastava, Devashish; Spaniol, Maggie A.; Abosch, Aviva

    2011-01-01

    Magnetic resonance imaging (MRI) of patients with implanted deep brain stimulation (DBS) devices poses a challenge for healthcare providers. As a consequence of safety concerns about magnetic field interactions with the device, induced electrical currents and thermal damage due to radiofrequency heating, a number of stringent guidelines have been proposed by the device manufacturer. Very few detailed investigations of these safety issues have been published to date, and the stringent manufacturer guidelines have gone unchallenged, leading some hospitals and imaging centers around the world to ban or restrict the use of MRI in DBS patients. The purpose of this review is to stimulate research towards defining appropriate guidelines for the use of MRI in patients with DBS. Additionally, this review is intended to help healthcare providers and researchers make sound clinical judgments about the use of MRI in the setting of implanted DBS devices. PMID:21494064

  2. Electrical stimulation causes rapid changes in electrode impedance of cell-covered electrodes

    PubMed Central

    Newbold, Carrie; Richardson, Rachael; Millard, Rodney; Seligman, Peter; Cowan, Robert; Shepherd, Robert

    2011-01-01

    Animal and clinical observations of a reduction in electrode impedance following electrical stimulation encouraged the development of an in vitro model of the electrode-tissue interface. This model was used previously to show an increase in impedance with cell and protein cover over electrodes. In this paper, the model was used to assess the changes in electrode impedance and cell cover following application of a charge-balanced biphasic current pulse train. Following stimulation, a large and rapid drop in total impedance (Zt) and access resistance (Ra) occurred. The magnitude of this impedance change was dependent on the current amplitude used, with a linear relationship determined between Ra and the resulting cell cover over the electrodes. The changes in impedance due to stimulation were shown to be transitory, with impedance returning to pre-stimulation levels several hours after cessation of stimulation. A loss of cells over the electrode surface was observed immediately after stimulation suggesting that the level of stimulation applied was creating localised changes to cell adhesion. Similar changes in electrode impedance were observed for in vivo and in vitro work, thus helping to verify the in vitro model, although the underlying mechanisms may differ. A change in the porosity of the cellular layer was proposed to explain the alterations in electrode impedance in vitro. These in vitro studies provide insight into the possible mechanisms occurring at the electrode-tissue interface in association with electrical stimulation. PMID:21572219

  3. Experimental and theoretical characterization of the voltage distribution generated by deep brain stimulation

    PubMed Central

    Miocinovic, Svjetlana; Lempka, Scott F.; Russo, Gary S.; Maks, Christopher B.; Butson, Christopher R.; Sakaie, Ken E.; Vitek, Jerrold L.; McIntyre, Cameron C.

    2008-01-01

    Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinsons disease and shows great promise for numerous other disorders. While the fundamental purpose of DBS is to modulate neural activity with electric fields, little is known about the actual voltage distribution generated in the brain by DBS electrodes and as a result it is difficult to accurately predict which brain areas are directly affected by the stimulation. The goal of this study was to characterize the spatial and temporal characteristics of the voltage distribution generated by DBS electrodes. We experimentally recorded voltages around active DBS electrodes in either a saline bath or implanted in the brain of a non-human primate. Recordings were made during voltage-controlled and current-controlled stimulation. The experimental findings were compared to volume conductor electric field models of DBS parameterized to match the different experiments. Three factors directly affected the experimental and theoretical voltage measurements: 1) DBS electrode impedance, primarily dictated by a voltage drop at the electrode-electrolyte interface and the conductivity of the tissue medium, 2) capacitive modulation of the stimulus waveform, and 3) inhomogeneity and anisotropy of the tissue medium. While the voltage distribution does not directly predict the neural response to DBS, the results of this study do provide foundational building blocks for understanding the electrical parameters of DBS and characterizing its effects on the nervous system. PMID:19118551

  4. Penetrating multichannel stimulation and recording electrodes in auditory prosthesis research.

    PubMed

    Anderson, David J

    2008-08-01

    Microelectrode arrays offer the auditory systems physiologists many opportunities through a number of electrode technologies. In particular, silicon substrate electrode arrays offer a large design space including choice of layout plan, range of surface areas for active sites, a choice of site materials and high spatial resolution. Further, most designs can double as recording and stimulation electrodes in the same preparation. Scala tympani auditory prosthesis research has been aided by mapping electrodes in the cortex and the inferior colliculus to assess the CNS responses to peripheral stimulation. More recently silicon stimulation electrodes placed in the auditory nerve, cochlear nucleus and the inferior colliculus have advanced the exploration of alternative stimulation sites for auditory prostheses. Multiplication of results from experimental effort by simultaneously stimulating several locations, or by acquiring several streams of data synchronized to the same stimulation event, is a commonly sought after advantage. Examples of inherently multichannel functions which are not possible with single electrode sites include (1) current steering resulting in more focused stimulation, (2) improved signal-to-noise ratio (SNR) for recording when noise and/or neural signals appear on more than one site and (3) current source density (CSD) measurements. Still more powerful are methods that exploit closely-spaced recording and stimulation sites to improve detailed interrogation of the surrounding neural domain. Here, we discuss thin-film recording/stimulation arrays on silicon substrates. These electrode arrays have been shown to be valuable because of their precision coupled with reproducibility in an ever expanding design space. The shape of the electrode substrate can be customized to accommodate use in cortical, deep and peripheral neural structures while flexible cables, fluid delivery and novel coatings have been added to broaden their application. The use of iridium oxide as the neural interface site material has increased the efficiency of charge transfer for stimulation and lowered impedance for recording electrodes. PMID:18343062

  5. 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.

  6. 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

  7. Alexithymia in patients with Parkinson’s disease treated with DBS of the subthalamic nucleus: a case-control study

    PubMed Central

    Castelli, Lorys; Tonello, Debora; Rizzi, Laura; Zibetti, Maurizio; Lanotte, Michele; Lopiano, Leonardo

    2014-01-01

    Objectives: To evaluate the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on alexithymia, a deficit in affective regulation, comparing patients with Parkinson’s disease (PD) submitted to STN-DBS (DBS group) to PD patients not yet treated with STN-DBS (pre-DBS group) and to healthy participants (C group). Methods: We recruited 27 consecutive STN-DBS PD patients, 38 consecutive pre-DBS patients and 27 healthy participants. Patients were assessed for alexithymia (Toronto Alexithymia Scale), depression, [beck depression inventory (BDI)], and cognitive functions (reasoning, memory, attentional, and executive tests). Results: The DBS patients performed worse than the pre-DBS patients in the corsi’s block-tapping test, in the phonemic fluency task and in the Frontal Assessment Battery. Around 30% of DBS (29.6%) and pre-DBS (31.6%) patients resulted alexithymic, compared with 14.8% in the C group. The results pointed out significantly higher alexithymia scores in both the DBS and pre-DBS groups compared with the C group, while no difference emerged between the DBS and pre-DBS groups. Pre-DBS group showed a significantly higher BDI score than the C group, while DBS group did not. Conclusion: Although the results suggest that STN-DBS does not affect alexithymia, both the DBS and pre-DBS patients reported higher prevalence (about 30%) of alexithymia than did healthy subjects (14.8%). PMID:25352821

  8. 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

  9. Chronic neural stimulation with thin-film, iridium oxide electrodes.

    PubMed

    Weiland, J D; Anderson, D J

    2000-07-01

    Experiments were conducted to assess the effect of chronic stimulation on the electrical properties of the electrode-tissue system, as measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Silicon, micromachined probes with multiple iridium oxide stimulating electrodes (400-1600 micron 2) were implanted in guinea pig cortex. A 10-17 day post-operative recovery period was followed by five days of monopolar stimulation, two hours/electrode each day using biphasic, constant current stimulation (5-100 microA, 100 microseconds/phase). EIS and CV data were taken before and after stimulation. The post-stimulation impedance [at mid-range frequencies (100 Hz-100 kHz)] consistently and significantly decreased relative to prestimulation levels. Impedance magnitude increased permanently at low frequencies (< 100 Hz), correlating to a change in the charge storage capacity (the area under a cyclic voltammagram). Impedance magnitude significantly increased during the recovery period, though this increase could be mostly reversed by applying small currents. A mathematical model of the electrode-tissue system impedance was used to analyze in vivo behavior. The data and modeling results shows that applying charge to the electrode can consistently reduce the impedance of the electrode-tissue system. Analysis of explanted probes suggests that the interaction between the tissue and electrode is dependent on whether chronic pulses were applied. It is hypothesized that the interface between the tissue and metal is altered by current pulsing, resulting in a temporary impedance shift. PMID:10916262

  10. 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.

  11. 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.

  12. Patient-Specific Analysis of the Relationship Between the Volume of Tissue Activated During DBS and Verbal Fluency

    PubMed Central

    Mikos, A.; Bowers, D.; Noecker, A.M.; McIntyre, C.C.; Won, M.; Chaturvedi, A.; Foote, K.D.; Okun, M.S.

    2010-01-01

    Deep brain stimulation (DBS) for the treatment of advanced Parkinsons disease involves implantation of a lead with four small contacts usually within the subthalamic nucleus (STN) or globus pallidus internus (GPi). While generally safe from a cognitive standpoint, STN DBS has been commonly associated with a decrease in the speeded production of words, a skill referred to as verbal fluency. Virtually all studies comparing pre-surgical to post-surgical verbal fluency performance have detected a decrease with DBS. The decline may be attributable in part to the surgical procedures, yet the relative contributions of stimulation effects are not known. In the present study, we used patient-specific DBS computer models to investigate the effects of stimulation on verbal fluency performance. Specifically, we investigated relationships of the volume and locus of activated STN tissue to verbal fluency outcome. Stimulation of different electrode contacts within the STN did not affect total verbal fluency scores. However, models of activation revealed subtle relationships between the locus and volume of activated tissue and verbal fluency performance. At ventral contacts, more tissue activation inside the STN was associated with decreased letter fluency performance. At optimal contacts, more tissue activation within the STN was associated with improved letter fluency performance. These findings suggest subtle effects of stimulation on verbal fluency performance, consistent with the functional non-motor subregions/somatopy of the STN. PMID:20362061

  13. Surface-Patterned Electrode Bioreactor for Electrical Stimulation

    PubMed Central

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Numata, Keiji; Montouri-Sorrentino, Chrystina; Cannizzaro, Christopher; Voldman, Joel

    2013-01-01

    We present a microscale cell culture system with an interdigitated microarray of excimer-laser-ablated indium tin oxide electrodes for electrical stimulation of cultured cells. The system has been characterized in a range of geometeries and stimulation regimes via electrochemical impedance spectroscopy and used to culture primary cardiomyocytes and human adipose derived stem cells. Over 6 days of culture with electrical stimulation (2 ms duration, 1 Hz, 180 ?m wide electrodes with 200 ?m spacing), both cell types exhibited enhanced proliferation, elongation and alignment, and adipose derived stem cells exhibited higher numbers of Connexin-43-composed gap junctions. PMID:20221556

  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; Bhrle, Christian P.; Lenartz, Doris; Maarouf, Mohammad; Treuer, Harald; Mai, Jrgen 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. Matching geometry and stimulation parameters of electrodes for deep brain stimulation experiments--numerical considerations.

    PubMed

    Gimsa, Ulrike; Schreiber, Ute; Habel, Beate; Flehr, Jrgen; van Rienen, Ursula; Gimsa, Jan

    2006-01-30

    Deep brain stimulation, the electric stimulation of basal ganglia nuclei, is a treatment for movement disorders such as Parkinson's disease. The underlying mechanisms are studied in animals, e.g. rodents. Designs and materials of commercially available microelectrodes, as well as experimentally applied driving signals vary tremendously. We used finite integration modeling to compare the electric field and current density distributions induced by various electrodes. Current density or field strength "hot spots", which are located particularly at sites of high curvature and material interfaces coincided with corrosion and erosion at poles and insulation, respectively, as shown by scanning electron microscopy of stainless steel electrodes. Cell constants, i.e. geometry factors relating the electrode impedance to the specific medium conductivity, were calculated to determine the electrode voltage for a given stimulation current. Nevertheless, for electrodes of the same cell constant but of different geometry, current and field distributions may be very dissimilar. We found geometry-dependent limiting values of the stimulation current, above which electric tissue damage may occur. These values limit the reach of the stimulation signal for a given electrode geometry. Also, electrode geometries determine the shape of the stimulated tissue volume. This study provides tools for choosing the most appropriate geometry for targeting different-sized brain areas. PMID:16095718

  16. 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.

  17. Controlling Parkinson's disease with adaptive deep brain stimulation.

    PubMed

    Little, Simon; Pogosyan, Alek; Neal, Spencer; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Brown, Peter

    2014-01-01

    Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power. Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism. PMID:25077449

  18. 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. PMID:17946862

  19. Micro-Reaction Chamber Electrodes for Neural Stimulation and Recording

    PubMed Central

    Shanmugasundaram, Balaji; Gluckman, Bruce J.

    2012-01-01

    Biocompatible electrodes with smaller geometric area are preferred to improve the selectivity of the neural recording and stimulation applications. We introduce the concept of a micro-reaction chamber (µRC) in which a volume within the electrode back plane is used to confine and sequester the electrochemical reactions used for charge passage. The µRC electrode design helps decrease impedance and improves the charge storage capacity without altering the geometry of the active site. Here we demonstrate that µRC electrodes fabricated from 50 µm diameter microwire have significantly improved charge storage capacity and lowered impedance at physiologically relevant frequencies in phosphate buffered saline solution compared with other designs. PMID:22254394

  20. Non-rectangular waveforms for neural stimulation with practical electrodes

    PubMed Central

    Sahin, Mesut; Tie, Yanmei

    2013-01-01

    Historically the rectangular pulse waveform has been the choice for neural stimulation. The strengthduration curve is thus defined for rectangular pulses. Not much attention has been paid to alternative waveforms to determine if the pulse shape has an effect on the strengthduration relation. Similarly the charge injection capacity of neural electrodes has also been measured with rectangular pulses. In this study we questioned if non-rectangular waveforms can generate a stronger stimulation effect, when applied through practical electrodes, by minimizing the neural activation threshold and maximizing the charge injection capacity of the electrode. First, the activation threshold parameters were studied with seven different pulse shapes using computer simulations of a local membrane model. These waveforms were rectangular, linear increase and decrease, exponential increase and decrease, Gaussian, and sinusoidal. The chronaxie time was found to be longer with all the non-rectangular pulses and some provided more energy efficient stimulation than the rectangular waveform. Second, the charge injection capacity of titanium nitride microelectrodes was measured experimentally for the same waveforms. Linearly decreasing ramp provided the best charge injection for all pulse widths tested from 0.02 to 0.5 ms. Finally, the most efficient waveform that maximized the charge injection capacity of the electrode while providing the lowest threshold charge for neural activation was searched. Linear and exponential decrease, and Gaussian waveforms were found to be the most efficient pulse shapes. PMID:17873425

  1. Pulse-clamp technique for single neuron stimulation electrode characterization.

    PubMed

    van Ooyen, Andre; Zagolla, Volker G; Ulrich, Christian; Schnakenberg, Uwe

    2009-01-01

    Miniaturized electrodes, structures and devices are necessary to achieve high target selectivity during stimulation in single neuron networks, while significant charge transfer is still demanded. A reliable test method is required to evaluate charge injection capability for high resolution neural stimulation applications that demand both a large amount of charge injection and a small electrode size. A circuit designed for the pulse-clamp technique was employed to characterize the electrode charge-storage capability of microelectrodes of sizes smaller than 300 microm in diameter. The circuit allows different electrodes and surface modifications to be quickly and accurately compared. Pulse-clamp measurements are performed on planar microelectrodes in 154 mM phosphate buffered saline (PBS) solution with 400 micros long pulses at charges up to 40 nC. The pulse-clamp and cyclic voltammetry results of sputtered iridium oxide film (SIROF) electrodes of different sizes show charge losses of less than 3% and a superior reversible charge injection capability compared to platinum microelectrodes of the same size, even at higher charge density levels. PMID:19964763

  2. Regional Personalized Electrodes to Select Transcranial Current Stimulation Target

    PubMed Central

    Tecchio, Franca; Cancelli, A.; Cottone, C.; Tomasevic, L.; Devigus, B.; Zito, G.; Ercolani, Matilde; Carducci, F.

    2013-01-01

    Rationale: Personalizing transcranial stimulations promises to enhance beneficial effects for individual patients. Objective: To stimulate specific cortical regions by developing a procedure to bend and position custom shaped electrodes; to probe the effects on cortical excitability produced when the properly customized electrode is targeting different cortical areas. Method: An ad hoc neuronavigation procedure was developed to accurately shape and place the personalized electrodes on the basis of individual brain magnetic resonance images (MRI) on bilateral primary motor (M1) and somatosensory (S1) cortices. The transcranial alternating current stimulation (tACS) protocol published by Feurra et al. (2011b) was used to test the effects on cortical excitability of the personalized electrode when targeting S1 or M1. Results: Neuronal excitability as evaluated by tACS was different when targeting M1 or S1, with the General Estimating Equation model indicating a clear tCS Effect (p?stimulating electrode. Significance: Through multimodal brain investigations continuous efforts in understanding the neuronal changes related to specific neurological or psychiatric diseases become more relevant as our ability to build the compensating interventions improves. An important step forward on this path is the ability to target the specific cortical area of interest, as shown in the present pilot work. PMID:23626529

  3. Electrochemical and Electrophysiological Performance of Platinum Electrodes Within the Ninety-Nine-Electrode Stimulating Nerve Cuff.

    PubMed

    Pe?lin, Polona; Mehle, Andra; Karpe, Bla; Rozman, Janez

    2015-10-01

    The trend in neural prostheses using selective nerve stimulation for electrical stimulation therapies is headed toward single-part systems having a large number of working electrodes (WEs), each of which selectively stimulate neural tissue or record neural response (NR). The present article reviews the electrochemical and electrophysiological performance of platinum WE within a ninety-nine-electrode spiral cuff for selective nerve stimulation and recording of peripheral nerves, with a focus on the vagus nerve (VN). The electrochemical properties of the WE were studied in vitro using the electrochemical impedance spectroscopy (EIS) technique. The equivalent circuit model (ECM) of the interface between the WE and neural tissue was extracted from the EIS data and simulated in the time domain using a preset current stimulus. Electrophysiological performance of in-space and fiber-type highly selective vagus nerve stimulation (VNS) was tested using an isolated segment of a porcine VN and carotid artery as a reference. A quasitrapezoidal current-controlled pulse (stimulus) was applied to the VN or arterial segment using an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate B-fibers and minimize the stimulation of A-fibers. The EIS results revealed capacitive charge transfer predominance, which is a highly desirable property. Electrophysiological performance testing indicated the potential existence of certain parameters and waveforms of the stimulus for which the contribution of the A-fibers to the NR decreased slightly and that of the B-fibers increased slightly. Findings show that the design of the stimulating electrodes, based on the EIS and ECM results, could act as a useful tool for nerve cuff development. PMID:26471140

  4. 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.

  5. Mechanisms Determining Safety and Performance of Brain Stimulating Electrodes

    PubMed Central

    Andre, Dana Lynn; Shanmugasundaram, Balaji; Mason, Jonathan; Drapaca, Corina; Gluckman, Bruce J.

    2013-01-01

    Electrical current is widely used to interact with or stimulate neural systems. Current transduction from device to tissue is mediated at the electrode-tissue interface by capacitive charge and electrochemistry. This charge-passing-capacity is frequency dependent. While safety parameters have been established for high-frequencies, safety has not been fully determined for novel materials and pulse frequencies significantly lower than 100 Hz. We are explicitly interested in safety parameters and performance of charge passing at low frequencies (?100 Hz) for neural systems. We present a visual study of pH during charge passing for electrodeposited iridium oxide electrodes. Clear reaction-diffusion waves are observed that extend many hundreds of micrometers from the electrode surface. PMID:19964485

  6. Mechanisms determining safety and performance of brain stimulating electrodes.

    PubMed

    Andre, Dana Lynn; Shanmugasundaram, Balaji; Mason, Jonathan; Drapaca, Corina; Gluckman, Bruce J

    2009-01-01

    Electrical current is widely used to interact with or stimulate neural systems. Current transduction from device to tissue is mediated at the electrode-tissue interface by capacitive charge and electrochemistry. This charge-passing-capacity is frequency dependent. While safety parameters have been established for high-frequencies, safety has not been fully determined for novel materials and pulse frequencies significantly lower than 100 Hz. We are explicitly interested in safety parameters and performance of charge passing at low frequencies (<100 Hz) for neural systems. We present a visual study of pH during charge passing for electrodeposited iridium oxide electrodes. Clear reaction-diffusion waves are observed that extend many hundreds of micrometers from the electrode surface. PMID:19964485

  7. 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 these series resistance increases observed with retinal proximity could be used as a metric of stimulus electrode placement.

  8. Deep brain stimulation of the forniceal area enhances memory functions in experimental dementia: the role of stimulation parameters.

    PubMed

    Hescham, Sarah; Lim, Lee Wei; Jahanshahi, Ali; Steinbusch, Harry W M; Prickaerts, Jos; Blokland, Arjan; Temel, Yasin

    2013-01-01

    Deep brain stimulation (DBS) is currently being evaluated as a potential therapy in improving memory functions in Alzheimer's disease. The target for DBS and the stimulation parameters to be used are unknown. Here, we implanted bilateral electrodes in the vicinity of the fornix, a key element of the memory circuitry, and applied DBS with different stimulation frequencies and amplitudes in an experimental model of dementia. Rats received scopolamine, a muscarinic acetylcholine receptor antagonist, to mimic memory impairment. Rats were then tested in the object location task with the following conditions: (i) with attachment of stimulation cable (off stimulation), and (ii) with DBS at various amplitudes (50 μA, 100 μA and 200 μA), 100 μs pulse width and 100 Hz or 10 Hz stimulation frequency. DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that the fornix is not sensitive to the frequency of stimulation, but rather to current levels. With the most optimal stimulation parameter, we found no side-effects on anxiety levels and general motor activity. These findings identify the fornix as a key region in controlling spatial memory functions. DBS of this region, using tailored stimulation parameters, has the potential to improve memory functions in conditions characterised by memory impairment. PMID:22405739

  9. Fidelity of frequency and phase entrainment of circuit-level spike activity during DBS.

    PubMed

    Agnesi, Filippo; Muralidharan, Abirami; Baker, Kenneth B; Vitek, Jerrold L; Johnson, Matthew D

    2015-08-01

    High-frequency stimulation is known to entrain spike activity downstream and upstream of several clinical deep brain stimulation (DBS) targets, including the cerebellar-receiving area of thalamus (VPLo), subthalamic nucleus (STN), and globus pallidus (GP). Less understood are the fidelity of entrainment to each stimulus pulse, whether entrainment patterns are stationary over time, and how responses differ among DBS targets. In this study, three rhesus macaques were implanted with a single DBS lead in VPLo, STN, or GP. Single-unit spike activity was recorded in the resting state in motor cortex during VPLo DBS, in GP during STN DBS, and in STN and pallidal-receiving area of motor thalamus (VLo) during GP DBS. VPLo DBS induced time-locked spike activity in 25% (n = 15/61) of motor cortex cells, with entrained cells following 7.5 7.4% of delivered pulses. STN DBS entrained spike activity in 26% (n = 8/27) of GP cells, which yielded time-locked spike activity for 8.7 8.4% of stimulus pulses. GP DBS entrained 67% (n = 14/21) of STN cells and 32% (n = 19/59) of VLo cells, which showed a higher fraction of pulses effectively inhibiting spike activity (82.0 9.6% and 86.1 16.6%, respectively). Latency of phase-locked spike activity increased over time in motor cortex (58%, VPLo DBS) and to a lesser extent in GP (25%, STN DBS). In contrast, the initial inhibitory phase observed in VLo and STN during GP DBS remained stable following stimulation onset. Together, these data suggest that circuit-level entrainment is low-pass filtered during high-frequency stimulation, most notably for glutamatergic pathways. Moreover, phase entrainment is not stationary or consistent at the circuit level for all DBS targets. PMID:26084905

  10. 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. PMID:22428054

  11. Ultra-nanocrystalline diamond electrodes: optimization towards neural stimulation applications

    NASA Astrophysics Data System (ADS)

    Garrett, David J.; Ganesan, Kumaravelu; Stacey, Alastair; Fox, Kate; Meffin, Hamish; Prawer, Steven

    2012-02-01

    Diamond is well known to possess many favourable qualities for implantation into living tissue including biocompatibility, biostability, and for some applications hardness. However, conducting diamond has not, to date, been exploited in neural stimulation electrodes due to very low electrochemical double layer capacitance values that have been previously reported. Here we present electrochemical characterization of ultra-nanocrystalline diamond electrodes grown in the presence of nitrogen (N-UNCD) that exhibit charge injection capacity values as high as 163 C cm-2 indicating that N-UNCD is a viable material for microelectrode fabrication. Furthermore, we show that the maximum charge injection of N-UNCD can be increased by tailoring growth conditions and by subsequent electrochemical activation. For applications requiring yet higher charge injection, we show that N-UNCD electrodes can be readily metalized with platinum or iridium, further increasing charge injection capacity. Using such materials an implantable neural stimulation device fabricated from a single piece of bio-permanent material becomes feasible. This has significant advantages in terms of the physical stability and hermeticity of a long-term bionic implant.

  12. Cognition and Mood in Parkinson Disease in STN versus GPi DBS: The COMPARE Trial

    PubMed Central

    Okun, Michael S.; Fernandez, Hubert H.; Wu, Samuel S.; Kirsch-Darrow, Lindsey; Bowers, Dawn; Bova, Frank; Suelter, Michele; Jacobson, Charles E.; Wang, Xinping; Gordon, Clifford W.; Zeilman, Pam; Romrell, Janet; Martin, Pam; Ward, Herbert; Rodriguez, Ramon L.; Foote, Kelly D.

    2009-01-01

    Objective There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD). Methods Fifty-two subjects with moderate-to-advanced PD were randomized to either unilateral STN or GPi DBS. Right or alternatively left sided stimulation was chosen to address the side of the body with the most bothersome symptoms. The co-primary outcome measures were the change in the 8 subscales of the Visual Analog Mood Scale (VAMS), and the change in the 2 versions of verbal fluency (i.e. semantic and letter), at 7 months post-DBS in the optimal setting compared to the pre-DBS state. In addition, at 7 months post-DBS, after subjects underwent initial evaluation off medications and on optimized DBS therapy, they were tested in four randomized and counterbalanced conditions (optimal DBS, ventral DBS, dorsal DBS, and off DBS) while remaining off medication. Secondary outcome measures then compared the differences in the VAMS items and verbal fluency subscales within the 4 DBS conditions at 7 months, and the change in the VAMS items and verbal fluency subscales from the pre-DBS state to the other 3 DBS conditions (ventral, dorsal and off ) at 7 months. Results Forty-five subjects (23 GPi and 22 STN) completed the protocol. The study revealed no significant difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes from pre- to post-DBS in the optimal setting (Hotelling's T2 test: p=0.16 and 0.08 respectively). When comparing the 4 DBS conditions at 7 months, subjects in both targets were less “happy”, less “energetic” and more “confused” when stimulated ventrally to the optimal stimulation site. When comparing the other 3 DBS conditions (ventral, dorsal and off DBS) to the pre-DBS state, the STN group showed a larger deterioration of letter verbal fluency scores than the GPi group, especially in the off DBS state. A 12-point mean improvement in the UPDRS motor subscale was seen post DBS, but there was no significant difference between targets. Interpretations There were no significant differences in in the co-primary outcome measures of mood and cognition between STN and GPi in the optimal DBS state.. However, adverse mood effects were noted when stimulating ventrally to the optimal site in both targets. Furthermore, a worsening for letter verbal fluency was noted in the 3 non-optimal post-DBS states in the STN target only. The persistence of deterioration in verbal fluency in the off DBS state at 7 months is, suggestive of a surgical rather than a stimulation-induced effect at the STN target. STN and GPi DBS resulted in similar motor improvement. PMID:19288469

  13. 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

  14. 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.

  15. Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

    PubMed Central

    Johnson, Matthew D.; Miocinovic, Svjetlana; McIntyre, Cameron C.; Vitek, Jerrold L.

    2008-01-01

    Summary Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. In this review three questions, essential to understanding the mechanisms of DBS, are discussed: 1) how does DBS affect neuronal tissue in the vicinity of the active electrode(s); 2) how do these changes translate into therapeutic benefit on motor symptoms; and 3) how do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view and suggested that while somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. While promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool. PMID:18394571

  16. Development of very large electrode arrays for epiretinal stimulation (VLARS)

    PubMed Central

    2014-01-01

    Background Retinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments. Methods Large area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices. Results Large area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices. Conclusions Large flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity. PMID:24502253

  17. 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

  18. 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

    2015-01-01

    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

  19. 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.

  20. Stimulation Stability and Selectivity of Chronically Implanted Multicontact Nerve Cuff Electrodes in the Human Upper Extremity

    PubMed Central

    Polasek, Katharine H.; Hoyen, Harry A.; Keith, Michael W.; Kirsch, Robert F.; Tyler, Dustin J.

    2010-01-01

    Nine spiral nerve cuff electrodes were implanted in two human subjects for up to three years with no adverse functional effects. The objective of this study was to look at the long term nerve and muscle response to stimulation through nerve cuff electrodes. The nerve conduction velocity remained within the clinically accepted range for the entire testing period. The stimulation thresholds stabilized after approximately 20 weeks. The variability in the activation over time was not different from muscle-based electrodes used in implanted functional electrical stimulation systems. Three electrodes had multiple, independent contacts to evaluate selective recruitment of muscles. A single muscle could be selectively activated from each electrode using single-contact stimulation and the selectivity was increased with the use of field steering techniques. The selectivity after three years was consistent with selectivity measured during the implant surgery. Nerve cuff electrodes are effective for chronic muscle activation and multichannel functional electrical stimulation in humans. PMID:19775987

  1. Closed-loop cortical neuromodulation in Parkinson's disease: An alternative to deep brain stimulation?

    PubMed

    Beuter, Anne; Lefaucheur, Jean-Pascal; Modolo, Julien

    2014-05-01

    Deep brain stimulation (DBS) is usually performed to treat advanced Parkinson's disease (PD) patients with electrodes permanently implanted in basal ganglia while the stimulator delivers electrical impulses continuously and independently of any feedback (open-loop stimulation). Conversely, in closed-loop stimulation, electrical stimulation is delivered as a function of neuronal activities recorded and analyzed online. There is an emerging development of closed-loop DBS in the treatment of PD and a growing discussion about proposing cortical stimulation rather than DBS for this purpose. Why does it make sense to "close the loop" to treat parkinsonian symptoms? Could closed-loop stimulation applied to the cortex become a valuable therapeutic strategy for PD? Can mathematical modeling contribute to the development of this technique? We review the various evidences in favor of the use of closed-loop cortical stimulation for the treatment of advanced PD, as an emerging technique which might offer substantial clinical benefits for PD patients. PMID:24555921

  2. 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.

  3. Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

    PubMed Central

    Nowak, Karl; Mix, Eilhard; Gimsa, Jan; Strauss, Ulf; Sriperumbudur, Kiran Kumar; Benecke, Reiner; Gimsa, Ulrike

    2011-01-01

    Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation. PMID:21603182

  4. The mechanisms of action of deep brain stimulation and ideas for the future development.

    PubMed

    Udupa, Kaviraja; Chen, Robert

    2015-10-01

    Deep brain stimulation (DBS) has been used as a treatment of movement disorders such as Parkinson's disease, dystonia, and essential tremor for over twenty years, and is a promising treatment for depression and epilepsy. However, the exact mechanisms of action of DBS are still uncertain, although different theories have emerged. This review summarizes the current understanding in this field. Different modalities used to investigate DBS such as electrophysiological, imaging and biochemical studies have revealed different mechanisms of DBS. The mechanisms may also be different depending on the structure targeted, the disease condition or the animal model employed. DBS may inhibit the target neuronal networks but activate the efferent axons. It may suppress pathological rhythms or impose new rhythms associated with beneficial effects, and involves neuronal networks with widespread connections. Different neurotransmitter systems such as dopamine and GABA upregulation are involved in the effects of DBS. There are also technical advances to prolong the battery life and specific targeting based on new electrode designs with multiple contacts which have the ability to steer the current toward a specific direction. There is ongoing work in closed loop or adaptive DBS using neural oscillations to provide the feedback signals. These oscillations need to be better characterized in a wide variety of clinical settings in future studies. Individualization of DBS parameters based on neural oscillations may optimize the clinical benefits of DBS. PMID:26296674

  5. 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.

  6. 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 ?, 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

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

    PubMed

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

    2013-04-01

    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 ?, 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

  8. 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. PMID:20615406

  9. Effects of STN DBS on Memory Guided Force Control in Parkinsons Disease (June 2007)

    PubMed Central

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

    2008-01-01

    This study examined the control of elbow force in nine patients with Parkinsons disease when visual feedback was available and when visual feedback was removed to determine how medication (Meds) and unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) affect memory guided force control. Patients were examined in each of four treatment conditions: 1) off treatment; 2) Meds; 3) STN DBS; and 4) Meds plus STN DBS. With visual feedback available, there was no difference in force output across treatment conditions. When visual feedback was removed force output drifted under the target in both the off-treatment and the Meds conditions. However, when on STN DBS or Meds plus STN DBS force output drifted above the target. As such, only STN DBS had a significant effect on force output in the vision removed condition. Increased force output when on STN DBS may have occurred due to disruptions in the basal ganglia-thalamo-cortical circuitry. We suggest that modulation of output of the internal segment of the globus pallidus by STN DBS may drive the effect of STN DBS on memory guided force control. PMID:17601184

  10. A new generation of double-sided intramuscular electrodes for multi-channel recording and stimulation.

    PubMed

    Poppendieck, Wigand; Muceli, Silvia; Dideriksen, Jakob; Rocon, Eduardo; Pons, Jose Luis; Farina, Dario; Hoffmann, Klaus-Peter

    2015-08-01

    In this work, a new generation of intramuscular multi-channel electrode for EMG recording and muscle stimulation is presented. The electrode is based on double-sided polyimide microtechnology, and features electrode contacts on both sides of a thin polyimide filament. The structure is attached to a cannula, allowing insertion and application of the electrode system similar to conventional intramuscular wire electrodes. In the presented design, the electrode has 12 small recording sites on one side of the structure, and 3 large stimulation sites on the other side. Applications of the system include diagnosis and treatment of tremor. To this end, the electrode has been successfully tested in tremor patients. In the future, the concept will be extended to other fields of application including intraneural electrodes. PMID:26737937

  11. Comparison of the efficacy of unipolar and bipolar electrode configuration during subthalamic deep brain stimulation.

    PubMed

    Deli, Gabriella; Balas, Istvan; Nagy, Ferenc; Balazs, Eva; Janszky, Jozsef; Komoly, Samuel; Kovacs, Norbert

    2011-01-01

    Deep brain stimulation of the subthalamic nuclei (STN) is a well established treatment in advanced Parkinson's disease (PD). Based on the clinical efficacy and elicited side-effects, both unipolar and bipolar stimulation modes may be applied. Bipolar stimulation usually produces a more focused and therefore thinner area of tissue activated during stimulation than unipolar stimulation does. The primary aim of our clinical study was to quantify the different clinical efficacy between these two stimulation modes. Twenty-one patients with PD previously underwent bilateral STN DBS implantation were involved in the study. Approximately three years after the implantation, we evaluated rigidity, tremor and bradykinesia according to the Unified Parkinson's disease Rating Scale in a practically off condition. Keeping the cathode of the chronic stimulation setting constant, the amplitude of stimulation was changed between 0 and 3.6 V by 0.2 V steps. Subsequently, the improvements in rigidity, tremor and bradykinesia were compared between unipolar and bipolar modes using 60 μs pulse-width and 130 Hz frequency. Within the examined amplitude range, unipolar stimulation usually had a significantly higher efficacy than bipolar stimulation; however, also with a higher rate of side-effects (19% vs. 0%). Depending on the evaluated parkinsonian symptoms, the efficacy of uni- and bipolar stimulation was different. To achieve the same level of improvement during bipolar stimulation, approximately 0.4-0.5 V higher amplitude was required than in unipolar mode. However in some cases, the efficacy of bipolar stimulation was unable the reach that of unipolar stimulation within the examined amplitude range. PMID:21106431

  12. 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 materialsthe 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 ?m 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 ?m). 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.

  13. [Deep brain stimulation for movement disorders: indications, results and complications].

    PubMed

    Fleury, Vanessa; Vingerhoets, François; Horvath, Judit; Pollak, Pierre; Burkhard, Pierre

    2015-04-29

    Movement disorders such as Parkinson's disease (PD), essential tremor (ET) and dystonia can benefit from deep brain stimulation (DBS). DBS is considered when symptoms are disabling despite optimal medical therapy. Contraindications include dementia, uncontrolled psychiatric disease and/or comorbid conditions with potential for evolution. Targets are the subthalamic nucleus for PD, the ventral intermediate nucleus for ET and the globus pallidus internus for dystonia. The beneficial effet of DBS has been well documented for symptom control. Optimal target localization of the electrodes reduces the occurrence of side-effects. Stimulation-induced adverse effects can usually be abolished by turning the stimulation off, changing the active contact or other stimulation parameters. PMID:26062221

  14. Anaesthetic management of a patient with deep brain stimulation implant for radical nephrectomy.

    PubMed

    Khetarpal, Monica; Yadav, Monu; Kulkarni, Dilip; Gopinath, R

    2014-07-01

    A 63-year-old man with severe Parkinson's disease (PD) who had been implanted with deep brain stimulators into both sides underwent radical nephrectomy under general anaesthesia with standard monitoring. Deep brain stimulation (DBS) is an alternative and effective treatment option for severe and refractory PD and other illnesses such as essential tremor and intractable epilepsy. Anaesthesia in the patients with implanted neurostimulator requires special consideration because of the interaction between neurostimulator and the diathermy. The diathermy can damage the brain tissue at the site of electrode. There are no standard guidelines for the anaesthetic management of a patient with DBS electrode in situ posted for surgery. PMID:25197118

  15. Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex

    NASA Astrophysics Data System (ADS)

    Wang, Chun; Brunton, Emma; Haghgooie, Saman; Cassells, Kahli; Lowery, Arthur; Rajan, Ramesh

    2013-08-01

    Objective. Cortical neural prostheses with implanted electrode arrays have been used to restore compromised brain functions but concerns remain regarding their long-term stability and functional performance. Approach. Here we report changes in electrode impedance and stimulation thresholds for a custom-designed electrode array implanted in rat motor cortex for up to three months. Main Results. The array comprises four 2000 µm long electrodes with a large annular stimulating surface (7860-15700 µm2) displaced from the penetrating insulated tip. Compared to pre-implantation in vitro values there were three phases of impedance change: (1) an immediate large increase of impedance by an average of two-fold on implantation; (2) a period of continued impedance increase, albeit with considerable variability, which reached a peak at approximately four weeks post-implantation and remained high over the next two weeks; (3) finally, a period of 5-6 weeks when impedance stabilized at levels close to those seen immediately post-implantation. Impedance could often be temporarily decreased by applying brief trains of current stimulation, used to evoke motor output. The stimulation threshold to induce observable motor behaviour was generally between 75-100 µA, with charge density varying from 48-128 µC cm-2, consistent with the lower current density generated by electrodes with larger stimulating surface area. No systematic change in thresholds occurred over time, suggesting that device functionality was not compromised by the factors that caused changes in electrode impedance. Significance. The present results provide support for the use of annulus electrodes in future applications in cortical neural prostheses.

  16. Enhancement of fear extinction with deep brain stimulation: evidence for medial orbitofrontal involvement.

    PubMed

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

    2015-06-01

    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

  17. 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. PMID:25101288

  18. Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

    PubMed Central

    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. PMID:25101288

  19. 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. PMID:22823512

  20. Neural origin of evoked potentials during thalamic deep brain stimulation.

    PubMed

    Kent, Alexander R; Grill, Warren M

    2013-08-01

    Closed-loop deep brain stimulation (DBS) systems could provide automatic adjustment of stimulation parameters and improve outcomes in the treatment of Parkinson's disease and essential tremor. The evoked compound action potential (ECAP), generated by activated neurons near the DBS electrode, may provide a suitable feedback control signal for closed-loop DBS. The objectives of this work were to characterize the ECAP across stimulation parameters and determine the neural elements contributing to the signal. We recorded ECAPs during thalamic DBS in anesthetized cats and conducted computer simulations to calculate the ECAP of a population of thalamic neurons. The experimental and computational ECAPs were similar in shape and had characteristics that were correlated across stimulation parameters (R(2) = 0.80-0.95, P < 0.002). The ECAP signal energy increased with larger DBS amplitudes (P < 0.0001) and pulse widths (P < 0.002), and the signal energy of secondary ECAP phases was larger at 10-Hz than at 100-Hz DBS (P < 0.002). The computational model indicated that these changes resulted from a greater extent of neural activation and an increased synchronization of postsynaptic thalamocortical activity, respectively. Administration of tetrodotoxin, lidocaine, or isoflurane abolished or reduced the magnitude of the experimental and computational ECAPs, glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphonopentanoic acid (APV) reduced secondary ECAP phases by decreasing postsynaptic excitation, and the GABAA receptor agonist muscimol increased the latency of the secondary phases by augmenting postsynaptic hyperpolarization. This study demonstrates that the ECAP provides information about the type and extent of neural activation generated during DBS, and the ECAP may serve as a feedback control signal for closed-loop DBS. PMID:23719207

  1. 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 s/phase biphasic pulses, the threshold charge densities were 24.0 11.2 and 7.7 3.2 C cm-2 for 50 and 125 m 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.

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

    PubMed

    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 s/phase biphasic pulses, the threshold charge densities were 24.0 11.2 and 7.7 3.2 C cm(-2) for 50 and 125 m 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. PMID:21593545

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

    PubMed Central

    Vargas Luna, Jos Luis; Krenn, Matthias; Corts Ramrez, 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:24514569

  5. Spinal cord stimulation with percutaneous and plate electrodes: side effects and quantitative comparisons.

    PubMed

    North, R B; Lanning, A; Hessels, R; Cutchis, P N

    1997-01-15

    Spinal cord stimulation is limited by the uncomfortable side effects experienced by the patient as the amplitude of stimulation is increased. These side effects include local segmental paresthesias or motor responses, which are objectively demonstrable as frequency-following muscle contractions, attributable to dorsal root stimulation. The authors present evidence for another mechanism of stimulation-evoked discomfort, namely recruitment of small fibers in ligamentum flavum, which occurs when electrodes are inserted percutaneously and their contacts are exposed circumferentially; this does not occur with plate electrodes with insulated dorsal surfaces. In a consecutive series of 79 patients with postsurgical lumbar pain syndromes, percutaneous four-contact electrodes were tested at levels from T-8 through T-12. At one or more levels, 46% of patients described paravertebral, nonradiating discomfort, unaccompanied by frequency-following muscle contractions. This was observed most commonly at the T-8 and T-9 levels. The effect was ameliorated in some cases by using multiple cathodes in parallel, which reduced the current density at individual contacts. In 10 of these patients, this side effect interfered with an otherwise successful trial to such a degree that an insulated plate electrode was selected for permanent implantation at the same level as the percutaneous electrode. This eliminated the uncomfortable side effect completely in all patients. Intraoperative testing with the insulated plate electrode inverted (that is, contacts dorsal) reproduced the side effect in the majority of patients, indicating that structures dorsal to the electrode, such as fibers in ligamentum flavum, mediate the effect. Postoperative testing by computerized techniques demonstrated improved coverage of pain by stimulation paresthesias, with lower stimulation power requirements, using the insulated plate electrode. This technical limitation of percutaneous spinal cord stimulation electrodes, which may confound treatment if unrecognized, has been found to have a straightforward solution which indicates the underlying mechanism. PMID:15096024

  6. 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 Parkinsons 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

  7. 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.

  8. A reliable method for intracranial electrode implantation and chronic electrical stimulation in the mouse brain

    PubMed Central

    2013-01-01

    Background Electrical stimulation of brain structures has been widely used in rodent models for kindling or modeling deep brain stimulation used clinically. This requires surgical implantation of intracranial electrodes and subsequent chronic stimulation in individual animals for several weeks. Anchoring screws and dental acrylic have long been used to secure implanted intracranial electrodes in rats. However, such an approach is limited when carried out in mouse models as the thin mouse skull may not be strong enough to accommodate the anchoring screws. We describe here a screw-free, glue-based method for implanting bipolar stimulating electrodes in the mouse brain and validate this method in a mouse model of hippocampal electrical kindling. Methods Male C57 black mice (initial ages of 6–8 months) were used in the present experiments. Bipolar electrodes were implanted bilaterally in the hippocampal CA3 area for electrical stimulation and electroencephalographic recordings. The electrodes were secured onto the skull via glue and dental acrylic but without anchoring screws. A daily stimulation protocol was used to induce electrographic discharges and motor seizures. The locations of implanted electrodes were verified by hippocampal electrographic activities and later histological assessments. Results Using the glue-based implantation method, we implanted bilateral bipolar electrodes in 25 mice. Electrographic discharges and motor seizures were successfully induced via hippocampal electrical kindling. Importantly, no animal encountered infection in the implanted area or a loss of implanted electrodes after 4–6 months of repetitive stimulation/recording. Conclusion We suggest that the glue-based, screw-free method is reliable for chronic brain stimulation and high-quality electroencephalographic recordings in mice. The technical aspects described this study may help future studies in mouse models. PMID:23914984

  9. A multi-pad electrode based functional electrical stimulation system for restoration of grasp

    PubMed Central

    2012-01-01

    Background Functional electrical stimulation (FES) applied via transcutaneous electrodes is a common rehabilitation technique for assisting grasp in patients with central nervous system lesions. To improve the stimulation effectiveness of conventional FES, we introduce multi-pad electrodes and a new stimulation paradigm. Methods The new FES system comprises an electrode composed of small pads that can be activated individually. This electrode allows the targeting of motoneurons that activate synergistic muscles and produce a functional movement. The new stimulation paradigm allows asynchronous activation of motoneurons and provides controlled spatial distribution of the electrical charge that is delivered to the motoneurons. We developed an automated technique for the determination of the preferred electrode based on a cost function that considers the required movement of the fingers and the stabilization of the wrist joint. The data used within the cost function come from a sensorized garment that is easy to implement and does not require calibration. The design of the system also includes the possibility for fine-tuning and adaptation with a manually controllable interface. Results The device was tested on three stroke patients. The results show that the multi-pad electrodes provide the desired level of selectivity and can be used for generating a functional grasp. The results also show that the procedure, when performed on a specific user, results in the preferred electrode configuration characteristics for that patient. The findings from this study are of importance for the application of transcutaneous stimulation in the clinical and home environments. PMID:23009589

  10. 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 ?m, spaced 60 ?m 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 ?s, 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.

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

    PubMed Central

    Meijs, Suzan; Fjorback, Morten; Jensen, Carina; Srensen, Sren; 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 Gttingen minipigs. Four of these were used for electrical stimulation and electrochemical measurements. Five electrodes were kept in Ringer's solution at 37.5C, 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

  12. 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 responsethe 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.

  13. Electrode spanning with partial tripolar stimulation mode in cochlear implants.

    PubMed

    Wu, Ching-Chih; Luo, Xin

    2014-12-01

    The perceptual effects of electrode spanning (i.e., the use of nonadjacent return electrodes) in partial tripolar (pTP) mode were tested on a main electrode EL8 in five cochlear implant (CI) users. Current focusing was controlled by ? (the ratio of current returned within the cochlea), and current steering was controlled by ? (the ratio of current returned to the basal electrode). Experiment 1 tested whether asymmetric spanning with ??=?0.5 can create additional channels around standard pTP stimuli. It was found that in general, apical spanning (i.e., returning current to EL6 rather than EL7) elicited a pitch between those of standard pTP stimuli on main electrodes EL8 and EL9, while basal spanning (i.e., returning current to EL10 rather than EL9) elicited a pitch between those of standard pTP stimuli on main electrodes EL7 and EL8. The pitch increase caused by apical spanning was more salient than the pitch decrease caused by basal spanning. To replace the standard pTP channel on the main electrode EL8 when EL7 or EL9 is defective, experiment 2 tested asymmetrically spanned pTP stimuli with various ?, and experiment 3 tested symmetrically spanned pTP stimuli with various ?. The results showed that pitch increased with decreasing ? in asymmetric spanning, or with increasing ? in symmetric spanning. Apical spanning with ? around 0.69 and basal spanning with ? around 0.38 may both elicit a similar pitch as the standard pTP stimulus. With the same ?, the symmetrically spanned pTP stimulus was higher in pitch than the standard pTP stimulus. A smaller ? was thus required for symmetric spanning to match the pitch of the standard pTP stimulus. In summary, electrode spanning is an effective field-shaping technique that is useful for adding spectral channels and handling defective electrodes with CIs. PMID:24865767

  14. 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.

  15. 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 ?s 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

  16. 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 Gttingen 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 (6.10.4 kg; mean SEM) that was lower than the nonstimulated VMH-DBS animals (9.41.3 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

  17. 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 Gttingen 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 (6.10.4 kg; mean SEM) that was lower than the nonstimulated VMH-DBS animals (9.41.3 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

  18. Brain Stimulation in Neurology and Psychiatry

    PubMed Central

    Little, Simon; Brown, Peter

    2012-01-01

    Feedback control of deep brain stimulation (DBS) in Parkinson's disease has great potential to improve efficacy, reduce side effects, and decrease the cost of treatment. In this, the timing and intensity of stimulation are titrated according to biomarkers that capture current clinical state. Stimulation may be at standard high frequency or intelligently patterned to directly modify specific pathological rhythms. The search for and validation of appropriate feedback signals are therefore crucial. Signals recorded from the DBS electrode currently appear to be the most promising source of feedback. In particular, beta-frequency band oscillations in the local field potential recorded at the stimulation target may capture variation in bradykinesia and rigidity across patients, but this remains to be confirmed within patients. Biomarkers that reliably reflect other impairments, such as tremor, also need to be established. Finally, whether brain signals are causally important needs to be established before stimulation can be specifically patterned rather than delivered at empirically defined high frequency. PMID:22830645

  19. Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects.

    PubMed

    Mestre, Tiago A; Lang, Anthony E; Okun, Michael S

    2016-03-01

    Deep brain stimulation (DBS) is a well-established treatment option for movement disorders, especially for Parkinson's disease (PD). There is a need to determine the role of expectation of benefit and the use of placebo to better understand the effects of electrode placement including the (micro)lesion effect. These factors must be understood to better interpret and attribute the therapeutic value of DBS. In this review, we critically present currently available data on the placebo, nocebo, lessebo, and lesion effects in the context of DBS. We provide a discussion of strategies that have the potential for controlling these effects in the setting of future DBS trials. We conclude that there is a need to standardize definitions for nocebo and (micro)lesion effects and that there are intrinsic limitations in defining the effect of expectation of benefit in DBS. These issues will be challenging to overcome especially with current technology and available study designs. New stimulation paradigms, better study designs, and the use of adaptive closed-loop DBS devices may facilitate a more accurate assessment of the placebo, nocebo, and lessebo effects in future DBS trials. © 2016 International Parkinson and Movement Disorder Society. PMID:26952118

  20. Selectivity for specific cardiovascular effects of vagal nerve stimulation with a multi-contact electrode cuff.

    PubMed

    Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

    2013-01-01

    The cardiovascular system can be influenced by electrically stimulating the vagal nerve. Selectivity for specific cardiac fibers may be limited when stimulating at the cervical level. Our objective was to increase effectiveness and selectivity for cardiovascular effects of vagal nerve stimulation by using local bipolar stimulation in one nerve cross section using a multi-contact cuff instead of less localized stimulation using a tripolar ring electrode. Both types of cuff electrodes were compared with respect to their relative effects on R-R interval (RRI), P-Q interval (PQI), left ventricular contractility (LVC), and left ventricular pressure (P(LV)) in seven pigs. Stimulation using the optimal bipolar configuration on the multi-contact cuff significantly affected RRI, PQI, LVC, and P(LV), whereas stimulation with the ring electrode only significantly affected RRI and PQI. The cardiovascular parameters that could be significantly influenced varied between the bipolar configurations. These novel findings may be relevant for optimizing electrode configurations for clinical cardiac applications of vagal nerve stimulation. PMID:22987542

  1. Non-invasive measurement of the input-output properties of peripheral nerve stimulating electrodes.

    PubMed

    Grill, W M; Mortimer, J T

    1996-03-01

    A non-invasive method was developed to determine the input-output (I/O) properties of peripheral nerve stimulating electrodes. An apparatus was fabricated to measure the 3-dimensional (3-D) isometric torque generated at the cat ankle joint by electrical activation of the sciatic nerve. The performance of the apparatus was quantified, and the utility of the method was demonstrated by measuring the recruitment properties of multiple contact nerve cuff electrodes. Torque-twitch waveforms, recruitment curves of peak torque as a function of stimulus current amplitude, and 2-D joint torque vectors were used to analyze the recruitment properties of the cuff. The peak of the twitch torque was an accurate measure of excitation even for muscles having fibers with varying speeds of contraction. The evoked twitch waveforms and torque vectors generated by selective stimulation of individual nerve branches with a hook electrode were compared to those produced by stimulation of the nerve trunk with the cuff electrode. These data allowed determination of the regions of the nerve trunk that were activated by different electrode geometries and stimulus parameters. The positional stability of electrode recruitment properties could be quantified by measuring I/O characteristics at different limb positions. The methods described are useful for characterization of neural stimulating electrodes and for studies of motor system physiology. PMID:8815307

  2. Approach for tunneling the lead in deep brain stimulation.

    PubMed

    Fabiano, Andrew J; Plunkett, Robert J

    2010-06-01

    The implantation of a deep brain stimulator (DBS) is often a staged procedure that involves stereotactic placement of the neurostimulator electrode, followed by connection of the electrode to a pulse generator during a separate operation. The authors describe a practical technique for the retrograde tunneling of the stimulator lead during the initial electrode implantation procedure. After DBS electrode placement and securing of the lead, the lead is covered with a protective cap and boot, which are then folded back to tunnel a redundant loop of the lead in a retrograde fashion into a subgaleal pocket. This technique facilitates connection of the lead to the pulse generator connecting wire at the subsequent operation and may reduce lead damage. PMID:19630498

  3. 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. PMID:26231574

  4. Optimized multi-electrode stimulation increases focality and intensity at target

    NASA Astrophysics Data System (ADS)

    Dmochowski, Jacek P.; Datta, Abhishek; Bikson, Marom; Su, Yuzhuo; Parra, Lucas C.

    2011-08-01

    Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25cm2), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality and intensity as compared to previous solutions and is thus expected to translate into improved patient safety and increased clinical efficacy.

  5. 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. PMID:23852740

  6. Deep brain stimulation of the subthalamic nucleus in the 6-hydroxydopamine rat model of Parkinson's disease: effects on sensorimotor gating.

    PubMed

    Lindemann, Christoph; Krauss, Joachim K; Schwabe, Kerstin

    2012-04-21

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effectively used to treat motor symptoms in Parkinson's disease (PD). Recently more attention has been paid to behavioral disturbances caused by PD itself and by STN DBS. In the 6-hydroxydopamine (6-OHDA) PD rat model we investigated the effect of STN DBS on deficient prepulse inhibition (PPI) induced by the dopamine (DA) receptor agonist apomorphine, which is an operative measure for disturbed sensorimotor gating seen in certain neuropsychiatric disturbances. Male Sprague Dawley rats with bilateral lesions of the nigrostriatal DA system (striatal injection of 6-OHDA or vehicle for sham-lesion) were bilaterally implanted with electrodes for DBS into the STN. After determination of individual thresholds rats were stimulated (130Hz, 80μs pulse width) or sham-stimulated for epochs of six days. On the sixth day of each epoch rats were tested for PPI of the acoustic startle response after apomorphine or vehicle injection in a within randomized cross-over design. Stimulation of the STN improved PPI in vehicle-treated (control) rats, but deteriorated PPI after apomorphine treatment. This effect was more pronounced in sham-lesioned rats. Furthermore, in lesioned rats the startle reaction was marginally enhanced without effect of stimulation or apomorphine treatment. These data suggest that STN DBS interacts with dopaminergic action. With respect to functional neurosurgery, STN DBS alone may improve certain aspects of psychiatric disturbances, but may have a different impact when combined with dopaminergic medication. PMID:22330948

  7. Olfactory hallucinations elicited by electrical stimulation via subdural electrodes: effects of direct stimulation of olfactory bulb and tract.

    PubMed

    Kumar, Gogi; Juhász, Csaba; Sood, Sandeep; Asano, Eishi

    2012-06-01

    In 1954, Penfield and Jasper briefly described that percepts of unpleasant odor were elicited by intraoperative electrical stimulation of the olfactory bulb in patients with epilepsy. Since then, few peer-reviewed studies have reported such phenomena elicited by stimulation mapping via subdural electrodes implanted on the ventral surface of the frontal lobe. Here, we determined what types of olfactory hallucinations could be reproduced by such stimulation in children with focal epilepsy. This study included 16 children (age range: 5 to 17 years) who underwent implantation of subdural electrodes to localize the presumed epileptogenic zone and eloquent areas. Pairs of electrodes were electrically stimulated, and clinical responses were observed. In case a patient reported a perception, she/he was asked to describe its nature. We also described the stimulus parameters to elicit a given symptom. Eleven patients reported a perception of smell in response to electrical stimulation while the remaining five did not. Nine patients perceived an unpleasant smell (like bitterness, smoke, or garbage) while two perceived a pleasant smell (like strawberry or good food). Such olfactory hallucinations were induced by stimulation proximal to the olfactory bulb or tract on either hemisphere but not by that of orbitofrontal gyri lateral to the medial orbital sulci. The range of stimulus parameters employed to elicit olfactory hallucinations was comparable to those for other sensorimotor symptoms. Our systematic study of children with epilepsy replicated stimulation-induced olfactory hallucinations. We failed to provide evidence that a positive olfactory perception could be elicited by conventional stimulation of secondary olfactory cortex alone. PMID:22554977

  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. PMID:25009455

  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. PMID:25009455

  10. Activation of ganglion cell axons following epiretinal electrical stimulation with hexagonal electrodes.

    PubMed

    Abramian, Miganoosh; Dokos, Socrates; Morley, John W; Lovell, Nigel H

    2010-01-01

    A hexagonal electrode configuration has been proposed as an advantageous alternative to conventional electrode arrangements used in retinal prosthesis design. In the present study, the aim was to characterize retinal ganglion cell axonal responses to epiretinal electrical stimulation. 50 and 125 microm disk electrodes, arranged in a hexagonal configuration, were tested using in vitro rabbit retinal preparations. 100 micros/phase anodic-first biphasic current pulses were applied to the inner retinal surface, and ganglion cell responses were recorded differentially with extracellular microelectrodes. Axonal activation thresholds were 4.7 2.5 microA for 50 microm, and 9.3 4.0 microA for 125 microm electrodes. With anodic monophasic pulses there was a 3.3 0.8 times increase in threshold, compared to anodic-first biphasic stimulation. Thresholds increased up to 20 times when stimulating electrodes were lifted 100 microm above the retinal surface. Overall, axonal activation thresholds were within the safe charge injection limits for platinum electrodes, given that these electrodes were positioned in close proximity to the retinal surface. PMID:21095832

  11. Deep brain stimulation in critical care conditions.

    PubMed

    Franzini, Angelo; Cordella, Roberto; Rizzi, Michele; Marras, Carlo E; Messina, Giuseppe; Zorzi, Giovanna; Caldiroli, Dario

    2014-04-01

    Some neurological conditions require admission to an intensive care unit (ICU) where deep sedation and mechanical ventilation are administered to improve the patient's condition. Nevertheless, these treatments are not always helpful in disease control. At this stage, deep brain stimulation (DBS) could become a viable alternative in the treatment of critical neurological conditions with long-lasting clinical benefit. The value of deep brain stimulation has been investigated in the treatment of patients who had undergone surgical electrode implants as an emergency procedure to treat acute life-threatening conditions requiring admission to neurological ICU (NICU). A before-and-after perspective study was examined of seven patients who were treated with DBS for status dystonicus (SD) and post-stroke severe hemiballismus. Bilateral globus pallidus internus (GPi) DBS was performed in five SD patients and unilateral ventralis oralis anterior and posterior (Voa/Vop) nucleus of the thalamus DBS in two post-stroke hemiballismus patients. Bilateral GPi-DBS allowed SD resolution in a time lapse varying from 1 week to 3 months. No clear improvements compared to the baseline clinical condition were observed. Unilateral Voa/Vop-DBS intervention controlled hemiballismus after 10 h, and the patient was discharged in 2 days. The other patient was transferred from the NICU to the neurosurgery ward after 13 days. No surgical complications were observed in any of the above procedures. Neurostimulation procedures could represent a valuable choice in critical care conditions, when involuntary movements are continuous, life-threatening and refractory to intensive care procedures. DBS is feasible, safe and effective in selected cases. PMID:24292857

  12. 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 visual prosthesis, while maintaining low power consumption. PMID:23991175

  13. The application of vagus nerve stimulation and deep brain stimulation in depression.

    PubMed

    Mohr, Pavel; Rodriguez, Mabel; Slav?kov, Anna; Hanka, Jan

    2011-01-01

    Despite the progress in the pharmacotherapy of depression, there is a substantial proportion of treatment-resistant patients. Recently, reversible invasive stimulation methods, i.e. vagus nerve stimulation (VNS) and deep brain stimulation (DBS), have been introduced into the management of treatment-resistant depression (TRD). VNS has already received regulatory approval for TRD. This paper reviews the available clinical evidence and neurobiology of VNS and DBS in TRD. The principle of VNS is a stimulation of the left cervical vagus nerve with a programmable neurostimulator. VNS was examined in 4 clinical trials with 355 patients. VNS demonstrated steadily increasing improvement with full benefit after 6-12 months, sustained up to 2 years. Patients who responded best had a low-to-moderate antidepressant resistance. However, the primary results of the only controlled trial were negative. DBS involves stereotactical implantation of electrodes powered by a pulse generator into the specific brain regions. For depression, the targeted areas are the subthalamic nucleus, internal globus pallidus, ventral internal capsule/ventral striatum, the subgenual cingulated region, and the nucleus accumbens. Antidepressant effects of DBS were examined in case series with a total number of 50 TRD patients. Stimulation of different brain regions resulted in a reduction of depressive symptoms. The clinical data on the use of VNS and DBS in TRD are encouraging. The major contribution of the methods is a novel approach that allows for precise targeting of the specific brain areas, nuclei and circuits implicated in the etiopathogenesis of neuropsychiatric disorders. For clinical practice, it is necessary to identify patients who may best benefit from VNS or DBS. PMID:21811087

  14. Two-Component Hearing Sensations Produced by Two-Electrode Stimulation in the Cochlea of a Deaf Patient

    NASA Astrophysics Data System (ADS)

    Tong, Y. C.; Dowell, R. C.; Blamey, P. J.; Clark, G. M.

    1983-02-01

    Dissimilarities in perception elicited by stimulation with two electrodes were estimated. A two-dimensional spatial configuration was found to be suitable to represent the dissimilarity data, and the two dimensions could be interpreted as corresponding to the position of the apical and basal electrode of the two-electrode combination. A speech-processing strategy that converts acoustic, first and second formants to two-electrode stimulation is proposed.

  15. Design and fabrication of a multi-electrode array for spinal cord epidural stimulation.

    PubMed

    Chang, Chih-Wei; Lo, Yi-Kai; Gad, Parag; Edgerton, Reggie; Liu, Wentai

    2014-01-01

    A detailed design, fabrication, characterization and test of a flexible multi-site platinum/polyimide based electrode array for electrical epidural stimulation in spinal cord prosthesis is described in this paper. Carefully designed 8.4 ?m-thick structure fabrication flow achieves an electrode surface modification with 3.8 times enhanced effective surface area without extra process needed. Measured impedance and phase of two type of electrodes are 2.350.21 K? and 2.100.11 K?, -34.258.07 and -27.718.27 at 1K Hz, respectively. The fabricated arrays were then in-vitro tested by a multichannel neural stimulation system in physiological saline to validate the capability for electrical stimulation. The measured channel isolation on adjacent electrode is about -34dB. Randles cell model was used to investigate the charging waveforms, the model parameters were then extracted by various methods. The measured charge transfer resistance, double layer capacitance, and solution resistance are 1.9 K?, 220 nF and 15 K?, respectively. The results show that the fabricated array is applicable for electrical stimulation with well characterized parameters. Combined with a multichannel stimulator, this system provides a full solution for versatile neural stimulation applications. PMID:25571566

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

    PubMed

    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 s/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 of the ECAP as a feedback signal for the tuning of DBS parameters. PMID:22510375

  17. 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 of the ECAP as a feedback signal for the tuning of DBS parameters.

  18. Gait and postural instability in Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

    PubMed

    Johnsen, Erik Lisbjerg

    2011-10-01

    In late stage Parkinson's disease (PD), medical treatment may not control the symptoms adequately, and the patient may become eligible for bilateral high frequency deep brain stimulation (DBS) in the subthalamic nucleus (STN). The effect of STN DBS on gait and postural instability is not always as predictable as the effect on clinical symptoms tremor, rigidity and bradykinesia. This may relate to the type of gait disorder or the stimulating electrode localization in the STN. We sought to evaluate the effect of STN DBS on gait performance during overground walking and gait initiation--assessed with 3D optokinetic movement analyses--and to compare the DBS effect with stimulation site localized on peri-operative MRI. The stimulation sites were grouped according to STN borders visualised on pre-operative MRI, and the active stimulation site was compared with clinical improvement and gait parameters. STN DBS is associated with improved movement amplitude while movement duration may be unaffected by both disease and stimulation. This may imply an improvement primarily on hypokinesia including gait hypokinesia. PMID:21975157

  19. 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. PMID:25810510

  20. Deep Brain Stimulation of Different Pedunculopontine Targets in a Novel Rodent Model of Parkinsonism

    PubMed Central

    Winn, Philip

    2015-01-01

    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. PMID:25810510

  1. Microsample analyses via DBS: challenges and opportunities.

    PubMed

    Henion, Jack; Oliveira, Regina V; Chace, Donald H

    2013-10-01

    The use of DBS is an appealing approach to employing microsampling techniques for the bioanalysis of samples, as has been demonstrated for the past 50 years in the metabolic screening of metabolites and diseases. In addition to its minimally invasive sample collection procedures and its economical merits, DBS microsampling benefits from the very high sensitivity, selectivity and multianalyte capabilities of LC-MS, which has been especially well demonstrated in newborn screening applications. Only a few microliters of a biological fluid are required for analysis, which also translates to significantly reduced demands on clinical samples from patients or from animals. Recently, the pharmaceutical industry and other arenas have begun to explore the utility and practicality of DBS microsampling. This review discusses the basis for why DBS techniques are likely to be part of the future, as well as offering insights into where these benefits may be realized. PMID:24138627

  2. Effects of STN DBS on Rigidity in Parkinsons Disease

    PubMed Central

    Shapiro, Mark B.; Vaillancourt, David E.; Sturman, Molly M.; Metman, Leo Verhagen; Bakay, Roy A. E.; Corcos, Daniel M.

    2008-01-01

    We quantified the effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and medication on Parkinsonian rigidity using an objective measure of work about the elbow joint during a complete cycle of imposed 1-Hz sinusoidal oscillations. Resting and activated rigidity were analyzed in four experimental conditions: 1) off treatment; 2) on DBS; 3) on medication; and 4) on DBS plus medication. Rigidity at the elbow joint was also assessed using the Unified Parkinsons Disease Rating Scale (UPDRS). We tested ten patients who received STN DBS and ten age-matched neurologically healthy control subjects. The activated rigidity condition increased work in both Parkinsons disease (PD) patients and control subjects. In PD patients, STN DBS reduced both resting and activated rigidity as indicated by work and the UPDRS rigidity score. This is the first demonstration that STN stimulation reduces rigidity using an objective measure such as work. In contrast, the presurgery dose of antiparkinsonian medication did not significantly improve the UPDRS rigidity score and reduced work only in the activated rigidity condition. Our results suggest that STN DBS may be more effective in alleviating rigidity in the upper limb of PD patients than medications administered at presurgery dosage level. PMID:17601186

  3. Effects of anterior thalamic nucleus deep brain stimulation in chronic epileptic rats.

    PubMed

    Covolan, Luciene; de Almeida, Antônio-Carlos G; 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

  4. 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

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

    PubMed Central

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

    2013-01-01

    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. Here, we have compared the effect of single-electrode stimulation at sub-threshold levels to the effect of stimulating as many as seven electrodes in combination. 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%). 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. PMID:23985904

  6. 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.

  7. 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.

  8. 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 ?m 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

  9. 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.

  10. An Implantable Versatile Electrode-Driving ASIC for Chronic Epidural Stimulation in Rats.

    PubMed

    Giagka, Vasiliki; Eder, Clemens; Donaldson, Nick; Demosthenous, Andreas

    2015-06-01

    This paper presents the design and testing of an electrode driving application specific integrated circuit (ASIC) intended for epidural spinal cord electrical stimulation in rats. The ASIC can deliver up to 1 mA fully programmable monophasic or biphasic stimulus current pulses, to 13 electrodes selected in any possible configuration. It also supports interleaved stimulation. Communication is achieved via only 3 wires. The current source and the control of the stimulation timing were kept off-chip to reduce the heat dissipation close to the spinal cord. The ASIC was designed in a 0.18- ?m high voltage CMOS process. Its output voltage compliance can be up to 25 V. It features a small core area (<;0.36 mm(2)) and consumes a maximum of 114 ?W during a full stimulation cycle. The layout of the ASIC was developed to be suitable for integration on the epidural electrode array, and two different versions were fabricated and electrically tested. Results from both versions were almost indistinguishable. The performance of the system was verified for different loads and stimulation parameters. Its suitability to drive a passive epidural 12-electrode array in saline has also been demonstrated. PMID:25134089

  11. Contribution of oxygen reduction to charge injection on platinum and sputtered iridium oxide neural stimulation electrodes.

    PubMed

    Cogan, Stuart F; Ehrlich, Julia; Plante, Timothy D; Gingerich, Marcus D; Shire, Douglas B

    2010-09-01

    The extent to which oxygen reduction occurs on sputtered iridium oxide (SIROF) and platinum neural stimulation electrodes was quantified by cyclic voltammetry and voltage-transient measurements in oxygen-saturated physiological saline. Oxygen reduction was the dominant charge-admittance reaction on platinum electrodes during slow-sweep-rate cyclic voltammetry, contributing approximately 12 mC/cm(2) (88% of total charge) to overall cathodal charge capacity. For a 300-nm-thick SIROF electrode, oxygen reduction was a minor reaction contributing 1.3 mC/cm(2), approximately 3% of total charge. During current pulsing with platinum electrodes, oxygen reduction was observed at a level of 7% of the total injected charge. There was no indication of oxygen reduction on pulsed SIROF electrodes. A sweep-rate-dependent contribution of oxygen reduction was observed on penetrating SIROF microelectrodes (nominal surface area 2000 microm(2)) and is interpreted in terms of rate-limited diffusion of oxygen in electrolyte that penetrates the junction between the insulation and electrode shaft. For typical neural stimulation pulses, no oxygen reduction could be observed on penetrating SIROF microelectrodes. Based on the in vivo concentration of dissolved oxygen, it is estimated that oxygen reduction on platinum microelectrodes will contribute less than 0.5% of the total injected charge and considerably less on SIROF electrodes. PMID:20515708

  12. Sensing-enabled hippocampal deep brain stimulation in idiopathic nonhuman primate epilepsy.

    PubMed

    Lipski, W J; DeStefino, V J; Stanslaski, S R; Antony, A R; Crammond, D J; Cameron, J L; Richardson, R M

    2015-02-15

    Epilepsy is a debilitating condition affecting 1% of the population worldwide. Medications fail to control seizures in at least 30% of patients, and deep brain stimulation (DBS) is a promising alternative treatment. A modified clinical DBS hardware platform was recently described (PC+S) allowing long-term recording of electrical brain activity such that effects of DBS on neural networks can be examined. This study reports the first use of this device to characterize idiopathic epilepsy and assess the effects of stimulation in a nonhuman primate (NHP). Clinical DBS electrodes were implanted in the hippocampus of an epileptic NHP bilaterally, and baseline local field potential (LFP) recordings were collected for seizure characterization with the PC+S. Real-time automatic detection of ictal events was demonstrated and validated by concurrent visual observation of seizure behavior. Seizures consisted of large-amplitude 8- to 25-Hz oscillations originating from the right hemisphere and quickly generalizing, with an average occurrence of 0.71 ± 0.15 seizures/day. Various stimulation parameters resulted in suppression of LFP activity or in seizure induction during stimulation under ketamine anesthesia. Chronic stimulation in the awake animal was studied to evaluate how seizure activity was affected by stimulation configurations that suppressed broadband LFPs in acute experiments. This is the first electrophysiological characterization of epilepsy using a next-generation clinical DBS system that offers the ability to record and analyze neural signals from a chronically implanted stimulating electrode. These results will direct further development of this technology and ultimately provide insight into therapeutic mechanisms of DBS for epilepsy. PMID:25429118

  13. 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 ? 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.

  14. Surface electrical stimulation for treating swallowing disorders after stroke: a review of the stimulation intensity levels and the electrode placements.

    PubMed

    Poorjavad, Marziyeh; Talebian Moghadam, Saeed; Nakhostin Ansari, Noureddin; Daemi, Mostafa

    2014-01-01

    Neuromuscular electrical stimulation (NMES) for treating dysphagia is a relatively new therapeutic method. There is a paucity of evidence about the use of NMES in patients with dysphagia caused by stroke. The present review aimed to introduce and discuss studies that have evaluated the efficacy of this method amongst dysphagic patients following stroke with emphasis on the intensity of stimulation (sensory or motor level) and the method of electrode placement on the neck. The majority of the reviewed studies describe some positive effects of the NMES on the neck musculature in the swallowing performance of poststroke dysphagic patients, especially when the intensity of the stimulus is adjusted at the sensory level or when the motor electrical stimulation is applied on the infrahyoid muscles during swallowing. PMID:24804147

  15. Surface Electrical Stimulation for Treating Swallowing Disorders after Stroke: A Review of the Stimulation Intensity Levels and the Electrode Placements

    PubMed Central

    Poorjavad, Marziyeh; Talebian Moghadam, Saeed; Daemi, Mostafa

    2014-01-01

    Neuromuscular electrical stimulation (NMES) for treating dysphagia is a relatively new therapeutic method. There is a paucity of evidence about the use of NMES in patients with dysphagia caused by stroke. The present review aimed to introduce and discuss studies that have evaluated the efficacy of this method amongst dysphagic patients following stroke with emphasis on the intensity of stimulation (sensory or motor level) and the method of electrode placement on the neck. The majority of the reviewed studies describe some positive effects of the NMES on the neck musculature in the swallowing performance of poststroke dysphagic patients, especially when the intensity of the stimulus is adjusted at the sensory level or when the motor electrical stimulation is applied on the infrahyoid muscles during swallowing. PMID:24804147

  16. Reward circuit DBS improves Parkinson's gait along with severe depression and OCD.

    PubMed

    Williams, Nolan R; Hopkins, Thomas R; Short, E Baron; Sahlem, Gregory L; Snipes, Jonathan; Revuelta, Gonzalo J; George, Mark S; Takacs, Istvan

    2016-04-01

    A 59-year-old Caucasian man with a past history of Parkinson's disease (PD) status post-bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), who also had treatment-resistant (TR) obsessive-compulsive disorder (OCD), and treatment-resistant depression (TRD), presented for further evaluation and management of his TR OCD. After an unsuccessful attempt to treat his OCD by reprogramming his existing STN DBS, he was offered bilateral ventral capsule/ventral striatum (VC/VS) DBS surgery. In addition to the expected improvement in OCD symptoms, he experienced significant improvement in both PD-related apathy and depression along with resolution of suicidal ideation. Furthermore, the patient's festinating gait dramatically improved. This case demonstrates that DBS of both the STN and VC/VS appears to have an initial signal of safety and tolerability. This is the first instance where both the STN and the VC/VS DBS targets have been implanted in an individual and the first case where a patient with PD has received additional DBS in mood-regulatory circuitry. PMID:26644268

  17. 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.

  18. 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

  19. Deep Brain Stimulation with Simultaneous fMRI in Rodents

    PubMed Central

    Younce, John Robert; Albaugh, Daniel L; Shih, Yen-Yu Ian

    2014-01-01

    In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS. PMID:24561922

  20. Deep brain stimulation with simultaneous FMRI in rodents.

    PubMed

    Younce, John Robert; Albaugh, Daniel L; Shih, Yen-Yu Ian

    2014-01-01

    In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal. Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS. PMID:24561922

  1. Amorphous and crystalline IrO 2 thin films as potential stimulation electrode coatings

    NASA Astrophysics Data System (ADS)

    Thanawala, Sachin S.; Baird, Ronald J.; Georgiev, Daniel G.; Auner, Gregory W.

    2008-06-01

    Amorphous and crystalline iridium oxide thin films with potential use as coating materials for stimulation electrodes were studied. Characterization of these films by cyclic voltammetry and impedance spectroscopy has revealed a considerable decrease in impedance and an increase in charge capacity of iridium oxide thin films after an electrochemical activation process in 0.9% NaCl solution. The surface morphology of these films was studied by scanning electron microscopy. The two types of IrO 2 films were also compared under conditions relevant to applications as stimulation electrodes. The results indicate that amorphous IrO 2 films have significantly higher charge storage capacity and lower impedance than crystalline IrO 2 films. This makes the amorphous films a preferable coating material for stimulation applications.

  2. Chronic posttraumatic movement disorder alleviated by insertion of meso-diencephalic deep brain stimulating electrode.

    PubMed

    Hooper, J; Simpson, P; Whittle, I R

    2001-10-01

    Incapacitating and drug-resistant posttraumatic movement disorders have successfully been treated by stereotactic thalamotomy. We describe the case of a young man with a posttraumatic hemiballismoid type movement disorder of the left arm, persistent for 2 years, who was selected for treatment with a thalamic deep brain stimulator. However, placement of the stimulating electrode tip at the junction of the zona incerta and subthalamic regions caused abolition of the movement disorder, and the pulse generator was not required. Reassessment over a 44-month period using multiple clinical and functional tests has confirmed continued benefit. This case adds to the reports of alleviation of movement disorders following either stereotactic thalamic mapping or placement of stimulating electrodes without macroscopic thalamic lesioning. PMID:11708550

  3. Measurement of evoked potentials during thalamic deep brain stimulation

    PubMed Central

    Kent, Alexander R.; Swan, Brandon D.; Brocker, David T.; Turner, Dennis A.; Gross, Robert E.; Grill, Warren M.

    2014-01-01

    Background Deep brain stimulation (DBS) treats the symptoms of several movement disorders, but optimal selection of stimulation parameters remains a challenge. The evoked compound action potential (ECAP) reflects synchronized neural activation near the DBS lead, and may be useful for feedback control and automatic adjustment of stimulation parameters in closed-loop DBS systems. Objectives Determine the feasibility of recording ECAPs in the clinical setting, understand the neural origin of the ECAP and sources of any stimulus artifact, and correlate ECAP characteristics with motor symptoms. Methods The ECAP and tremor response were measured simultaneously during intraoperative studies of thalamic DBS, conducted in patients who were either undergoing surgery for initial lead implantation or replacement of their internal pulse generator. Results There was large subject-to-subject variation in stimulus artifact amplitude, which model-based analysis suggested may have been caused by glial encapsulation of the lead, resulting in imbalances in the tissue impedance between the contacts. ECAP recordings obtained from both acute and chronically implanted electrodes revealed that specific phase characteristics of the signal varied systematically with stimulation parameters. Further, a trend was observed in some patients between the energy of the initial negative and positive ECAP phases, as well as secondary phases, and changes in tremor from baseline. A computational model of thalamic DBS indicated that direct cerebellothalamic fiber activation dominated the clinically measured ECAP, suggesting that excitation of these fibers is critical in DBS therapy. Conclusions This work demonstrated that ECAPs can be recorded in the clinical setting and may provide a surrogate feedback control signal for automatic adjustment of stimulation parameters to reduce tremor amplitude. PMID:25457213

  4. 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. PMID:22847280

  5. Underlying Neurobiology and Clinical Correlates of Mania Status-Post Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s disease: A Review of the Literature

    PubMed Central

    Chopra, Amit; Tye, Susannah J.; Lee, Kendall H.; Sampson, Shirlene; Matsumoto, Joseph; Adams, Andrea; Klassen, Bryan; Stead, Matt; Fields, Julie A.; Frye, Mark A

    2013-01-01

    Introduction Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson’s disease (PD). Methods We review the current literature to identify the clinical correlates associated with STN DBS-induced hypomania/mania in PD patients. Results Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male patients and/or early onset PD. Conclusion STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanism(s) of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight towards development of future DBS mood stabilization therapies. PMID:22450620

  6. Deep brain stimulation, ethics, and society.

    PubMed

    Bell, Emily; Racine, Eric

    2010-01-01

    Discussion surrounding ethical and social issues in deep brain stimulation (DBS) has increased. This article introduces a special section on the ethics of DBS in The Journal of Clinical Ethics. PMID:20866015

  7. Electrochemical Characterization of Implantable High Aspect Ratio Nanoparticle Platinum Electrodes for Neural Stimulations

    NASA Astrophysics Data System (ADS)

    Hu, Zhiyu; Zhou, Dao Min; Greenberg, Robert; Thundat, Thomas

    Two-dimensional (2D) and three-dimensional (3D) patternable conductive structures such as entire neural stimulation circuit are created by using metal nanoparticles and a nanopowder molding process. Fabricated structures retain a height-to-width ratio of up to 10:1. The described process is able to fuse the stimulating electrode, connection trace, and contact pad into one continuous, integrated structure where different sections can have different heights, widths, and shapes. The batch process is suitable for mass production, and the fabricated electrode is robust and very flexible. Additionally, the completed structure can be packed onto a biocompatible flexible substrate, such as poly-dimethylsiloxane, parylene, and polyimide as well as other temperature-sensitive or vacuum-sensitive materials at room temperature which make it more suitable for biomedical applications. Experimental data show that the electrodes and wires have about the same electrical resistivities as their bulk materials and desirable electrochemical properties, including low impedance. The nanoscale feature on the electrode surface enhanced the interface and contact quality between electrode and bio-substrate that led to better electrochemical performance.

  8. 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, 7נ12 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. PMID:22595310

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

    NASA Astrophysics Data System (ADS)

    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.

  10. 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.

  11. 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

  12. Evaluation of different stimulation and measurement patterns based on internal electrode: application in cardiac impedance tomography.

    PubMed

    Nasehi Tehrani, J; Oh, T I; Jin, C; Thiagalingam, A; McEwan, A

    2012-11-01

    The conductivity distribution around the thorax is altered during the cardiac cycle due to the blood perfusion, heart contraction and lung inflation. Previous studies showed that these bio-impedance changes are appropriate for non-invasive cardiac function imaging using Electrical Impedance Tomography (EIT) techniques. However, the spatial resolution is presently low. One of the main obstacles in cardiac imaging at the heart location is the large impedance variation of the lungs by respiration and muscles on the dorsal and posterior side of the body. In critical care units there is a potential to insert an internal electrode inside the esophagus directly behind the heart in the same plane of the external electrodes. The aim of the present study is to evaluate different current stimulation and measurement patterns with both external and internal electrodes. Analysis is performed with planar arrangement of 16 electrodes for a simulated 3D cylindrical tank and pig thorax model. In our study we evaluated current injection patterns consisting of adjacent, diagonal, trigonometric, and radial to the internal electrode. The performance of these arrangements was assessed using quantitative methods based on distinguishability, sensitivity and GREIT (Graz consensus Reconstruction algorithm for Electrical Impedance Tomography). Our evaluation shows that an internal electrode configuration based on the trigonometric injection patterns has better performance and improves pixel intensity of the small conductivity changes related to heart near 1.7 times in reconstructed images and also shows more stability with different levels of added noise. For the internal electrode, when we combined radial or adjacent injection with trigonometric injection pattern, we found an improvement in amplitude response. However, the combination of diagonal with trigonometric injection pattern deteriorated the shape deformation (correlation coefficient r=0.344) more than combination of radial and trigonometric injection (correlation coefficient r=0.836) for the perturbations in the area close to the center of the cylinder. We also find that trigonometric stimulation pattern performance is degraded in a realistic thorax model with anatomical asymmetry. For that reason we recommend using internal electrodes only for voltage measurements and as a reference electrode during trigonometric stimulation patterns in practical measurements. PMID:23017828

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

    NASA Astrophysics Data System (ADS)

    Kempe, Ren; 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.

  14. A Long Term Effects of a New Onset Psychosis after DBS Treated with Quetiapine in a Patient with Parkinson's Disease

    PubMed Central

    Perini, Giulia; Pizzighello, Silvia; Vestri, Alec; Ferri, Giovanni; Toffanin, Tommaso; Follador, Halima; Martinuzzi, Andrea

    2015-01-01

    Deep Brain Stimulation represents a therapeutic option for PD patients. In this paper, we present and discuss a case of acute delirium and psychosis manifesting after DBS in a 58-years-old man affected by Parkinson's Disease. We highlight the importance of an exhaustive psychiatric evaluation in candidates for DBS and we underline the severity and non-reversibility of some adverse events associated with the implantation, suggesting the use of Quetiapine in the management of these effects. Acute psychosis may be listed as a potential severe adverse event associated with DBS, even in patients without a clear cut previous history of psychiatric disorders. PMID:25670958

  15. Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform

    PubMed Central

    Hallfors, Nicholas; Khan, Asif; Dickey, Michael D.; Taylor, Anne Marion

    2015-01-01

    Electrical stimulation of nervous tissue is used clinically for the treatment of multiple neurological disorders and experimentally for basic research. With the increase of optical probes to record neuronal activity, simple and user-friendly methods are desired to stimulate neurons and their subcellular compartments for biological experimentation. Here we describe the novel integration of liquid metal electrodes with microfluidic culture platforms to accomplish this goal. We integrated electrode and cell channels into a single poly(dimethylsiloxane) (PDMS) chip, eliminating entirely the need to align electrodes with microchannels. We designed the electrode channels such that the metal can be injected by hand and when the device is non-covalently bound to glass. We demonstrated the biocompatibility of the electrodes for long-term cultures (12 days) using hippocampal neurons. We demonstrated the use of these electrodes to depolarize neurons and recorded neuronal activity using the calcium indicator dye, Fluo-4. We established optimal stimulation parameters that induce neuronal spiking without inducing damage. We showed that the liquid metal electrode evoked larger calcium responses in somata than bath electrodes using the same stimulus parameters. Lastly we demonstrated the use of these liquid metal electrodes to target and depolarize axons. In summary, the integration of liquid metal electrodes with neuronal culture platforms provides a user-friendly and targeted method to stimulate neurons and their subcellular compartments, thus providing a novel tool for future biological investigations. PMID:23232866

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

    PubMed

    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. PMID:20332553

  17. Local Glutamate Release in the Rat Ventral Lateral Thalamus Evoked by High-Frequency Stimulation

    PubMed Central

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

    2010-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:20332553

  18. 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

    2015-01-01

    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. PMID:25495574

  19. Aligned Nanofibers from Polypyrrole/Graphene as Electrodes for Regeneration of Optic Nerve via Electrical Stimulation.

    PubMed

    Yan, Lu; Zhao, Bingxin; Liu, Xiaohong; Li, Xuan; Zeng, Chao; Shi, Haiyan; Xu, Xiaoxue; Lin, Tong; Dai, Liming; Liu, Yong

    2016-03-23

    The damage of optic nerve will cause permanent visual field loss and irreversible ocular diseases, such as glaucoma. The damage of optic nerve is mainly derived from the atrophy, apoptosis or death of retinal ganglion cells (RGCs). Though some progress has been achieved on electronic retinal implants that can electrically stimulate undamaged parts of RGCs or retina to transfer signals, stimulated self-repair/regeneration of RGCs has not been realized yet. The key challenge for development of electrically stimulated regeneration of RGCs is the selection of stimulation electrodes with a sufficient safe charge injection limit (Qinj, i.e., electrochemical capacitance). Most traditional electrodes tend to have low Qinj values. Herein, we synthesized polypyrrole functionalized graphene (PPy-G) via a facile but efficient polymerization-enhanced ball milling method for the first time. This technique could not only efficiently introduce electron-acceptor nitrogen to enhance capacitance, but also remain a conductive platform-the π-π conjugated carbon plane for charge transportation. PPy-G based aligned nanofibers were subsequently fabricated for guided growth and electrical stimulation (ES) of RGCs. Significantly enhanced viability, neurite outgrowth and antiaging ability of RGCs were observed after ES, suggesting possibilities for regeneration of optic nerve via ES on the suitable nanoelectrodes. PMID:26926578

  20. PPNa-DBS for gait and balance disorders in Parkinson's disease: a double-blind, randomised study.

    PubMed

    Welter, Marie-Laure; Demain, Adele; Ewenczyk, Claire; Czernecki, Virginie; Lau, Brian; El Helou, Amine; Belaid, Hayat; Yelnik, Jrme; Franois, Chantal; Bardinet, Eric; Karachi, Carine; Grabli, David

    2015-06-01

    Gait and balance disorders are the major source of motor disabilities in advanced forms of Parkinson's disease (PD). Low-frequency stimulation of the pedunculopontine nucleus area (PPNa-DBS) has been recently proposed to treat these symptoms with variable clinical results. To further understand the effects of PPNa-DBS on resistant gait and balance disorders, we performed a randomised double-blind cross-over study in six PD patients. Evaluation included clinical assessment of parkinsonian disability, quality of life and neurophysiological recordings of gait. Evaluations were done 1 month before, 4 and 6 months after surgery with four double-blinded conditions assessed: with and without PPNa-DBS, with and without levodopa treatment. Four patients completed the study and two patients were excluded from the final analysis because of peri-operative adverse events (haematoma, infection). Clinically, the combination of PPNa-DBS and levodopa treatment produced a significant decrease of the freezing episodes. The frequency of falls also decreased in three out of four patients. From a neurophysiological point of view, PPNa-DBS significantly improved the anticipatory postural adjustments and double-stance duration, but not the length and speed of the first step. Interestingly, step length and speed improved after surgery without PPNa-DBS, suggesting that the lesioning effect of PPNa-DBS surgery alleviates parkinsonian akinesia. Quality of life was also significantly improved with PPNa-DBS. These results suggest that PPNa-DBS could improve gait and balance disorders in well-selected PD patients. However, this treatment may be riskier than others DBS surgeries in these patients with an advanced form of PD. PMID:25904205

  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 Feij

    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. Combined use of transcranial magnetic stimulation and metal electrode implants: a theoretical assessment of safety considerations

    NASA Astrophysics Data System (ADS)

    Golestanirad, Laleh; Rouhani, Hossein; Elahi, Behzad; Shahim, Kamal; Chen, Robert; Mosig, Juan R.; Pollo, Claudio; Graham, Simon J.

    2012-12-01

    This paper provides a theoretical assessment of the safety considerations encountered in the simultaneous use of transcranial magnetic stimulation (TMS) and neurological interventions involving implanted metallic electrodes, such as electrocorticography. Metal implants are subject to magnetic forces due to fast alternating magnetic fields produced by the TMS coil. The question of whether the mechanical movement of the implants leads to irreversible damage of brain tissue is addressed by an electromagnetic simulation which quantifies the magnitude of imposed magnetic forces. The assessment is followed by a careful mechanical analysis determining the maximum tolerable force which does not cause irreversible tissue damage. Results of this investigation provide useful information on the range of TMS stimulator output powers which can be safely used in patients having metallic implants. It is shown that conventional TMS applications can be considered safe when applied on patients with typical electrode implants as the induced stress in the brain tissue remains well below the limit of tissue damage.

  3. Neural electrode degradation from continuous electrical stimulation: comparison of sputtered and activated iridium oxide.

    PubMed

    Negi, Sandeep; Bhandari, Rajmohan; Rieth, Loren; Van Wagenen, Rick; Solzbacher, Florian

    2010-01-30

    The performance of neural electrodes in physiological fluid, especially in chronic use, is critical for the success of functional electrical stimulation devices. Tips of the Utah electrode arrays (UEAs) were coated with sputtered iridium oxide film (SIROF) and activated iridium oxide film (AIROF) to study the degradation during charge injection consistent with functional electrical stimulation (FES). The arrays were subjected to continuous biphasic, cathodal first, charge balanced (with equal cathodal and anodal pulse widths) current pulses for 7h (>1 million pulses) at a frequency of 50 Hz. The amplitude and width of the current pulses were varied to determine the damage threshold of the coatings. Degradation was characterized by scanning electron microscopy, inductively coupled plasma mass spectrometry, electrochemical impedance spectroscopy and cyclic voltammetry. The injected charge and charge density per phase were found to play synergistic role in damaging the electrodes. The damage threshold for SIROF coated electrode tips of the UEA was between 60 nC with a charge density of 1.9 mC/cm(2) per phase and 80 nC with a charge density of 1.0 mC/cm(2) per phase. While for AIROF coated electrode tips, the threshold was between 40 nC with a charge density of 0.9 mC/cm(2) per phase and 50 nC with a charge density of 0.5 mC/cm(2) per phase. Compared to AIROF, SIROF showed higher damage threshold and therefore is highly recommended to be used as a stimulation material. PMID:19878693

  4. Neural Electrode Degradation from Continuous Electrical Stimulation: Comparison of Sputtered and Activated Iridium Oxide

    PubMed Central

    Negi, Sandeep; Bhandari, Rajmohan; Rieth, Loren; Van Wagenen, Rick; Solzbacher, Florian

    2009-01-01

    The performance of neural electrodes in physiological fluid, especially in chronic use, is critical for the success of functional electrical stimulation devices. Tips of the Utah Electrode Arrays (UEA) were coated with sputtered iridium oxide film (SIROF) and activated iridium oxide film (AIROF) to study the degradation during charge injection consistent with functional electrical stimulation (FES). The arrays were subjected to continuous biphasic, cathodal first, charge balanced (with equal cathodal and anodal pulse widths) current pulses for 7 hours (> 1 million pulses) at a frequency of 50 Hz. The amplitude and width of the current pulses were varied to determine the damage threshold of the coatings. Degradation was characterized by scanning electron microscopy, inductively coupled plasma mass spectrometry, electrochemical impedance spectroscopy and cyclic voltammetry. The injected charge and charge density per phase were found to play synergistic role in damaging the electrodes. The damage threshold for SIROF coated electrode tips of the UEA was between 60 nC with a charge density of 1.9 mC/cm2 per phase and 80 nC with a charge density of 1.0 mC/cm2 per phase. While for AIROF coated electrode tips, the threshold was between 40 nC with a charge density of 0.9 mC/cm2 per phase, and 50 nC with a charge density of 0.5 mC/cm2 per phase. Compared to AIROF, SIROF showed higher damage threshold and therefore is highly recommended to be used as a stimulation material. PMID:19878693

  5. An ultra small array of electrodes for stimulating multiple inputs into a single neuron.

    PubMed

    Smith, Spencer L; Judy, Jack W; Otis, Thomas S

    2004-02-15

    We have developed an ultra small, translucent array of electrodes for use in the parasaggital cerebellar slice preparation. This positionable array is capable of stimulating multiple independent bundles of parallel fibers (PFs), which synapse onto a single Purkinje neuron. On a silicon substrate, a low-stress silicon nitride film was used both as a structural layer and as electrical insulation. Evaporated gold pads and interconnects were sandwiched between two such layers. A bulk anisotropic silicon etch released the individual arrays. The electrodes are supported within a 2-microm-thick cantilever of translucent silicon nitride. In one design, eight 4-microm-wide square electrodes are arranged on 8-microm-centers. Another design, half the scale of the first, was also tested. The array was mounted on a micromanipulator and can be visualized by an upright microscope. It can then be positioned in the dendritic arbor of a Purkinje neuron while not disturbing a recording pipette at the soma. Paired-pulse facilitation experiments have confirmed that the electrodes are capable of stimulating non-overlapping bundles of PFs. This device will be useful for exploring spatiotemporal synaptic integration in single neurons. Potential applications in experiments on cerebellar LTD are also discussed. PMID:14757351

  6. Deep brain stimulation: how does it work?

    PubMed

    Agnesi, Filippo; Johnson, Matthew D; Vitek, Jerrold L

    2013-01-01

    Chronic deep brain stimulation (DBS) has become a widely accepted surgical treatment for medication-refractory movement disorders and is under evaluation for a variety of neurological disorders. In order to create opportunities to improve treatment efficacy, streamline parameter selection, and foster new potential applications, it is important to have a clear and comprehensive understanding of how DBS works. Although early hypothesis proposed that high-frequency electrical stimulation inhibited neuronal activity proximal to the active electrode, recent studies have suggested that the output of the stimulated nuclei is paradoxically activated by DBS. Such regular, time-locked output is thought to override the transmission of pathological bursting and oscillatory activity through the stimulated nuclei, as well as inducing synaptic plasticity and network reorganization. This chapter reviews electrophysiological experiments, biochemical analyses, computer modeling and imaging studies positing that, although general principles exist, the therapeutic mechanism(s) of action depend both on the site of stimulation and on the disorder being treated. PMID:24112883

  7. Technological Advances in Deep Brain Stimulation.

    PubMed

    Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

    2015-01-01

    Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware. PMID:26406128

  8. How to Culture, Record and Stimulate Neuronal Networks on Micro-electrode Arrays (MEAs)

    PubMed Central

    Hales, Chadwick M.; Rolston, John D.; Potter, Steve M.

    2010-01-01

    For the last century, many neuroscientists around the world have dedicated their lives to understanding how neuronal networks work and why they stop working in various diseases. Studies have included neuropathological observation, fluorescent microscopy with genetic labeling, and intracellular recording in both dissociated neurons and slice preparations. This protocol discusses another technology, which involves growing dissociated neuronal cultures on micro-electrode arrays (also called multi-electrode arrays, MEAs). There are multiple advantages to using this system over other technologies. Dissociated neuronal cultures on MEAs provide a simplified model in which network activity can be manipulated with electrical stimulation sequences through the array's multiple electrodes. Because the network is small, the impact of stimulation is limited to observable areas, which is not the case in intact preparations. The cells grow in a monolayer making changes in morphology easy to monitor with various imaging techniques. Finally, cultures on MEAs can survive for over a year in vitro which removes any clear time limitations inherent with other culturing techniques.1 Our lab and others around the globe are utilizing this technology to ask important questions about neuronal networks. The purpose of this protocol is to provide the necessary information for setting up, caring for, recording from and electrically stimulating cultures on MEAs. In vitro networks provide a means for asking physiologically relevant questions at the network and cellular levels leading to a better understanding of brain function and dysfunction. PMID:20517199

  9. Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache.

    PubMed

    Fontaine, Denys; Lanteri-Minet, Michel; Ouchchane, Lemlih; Lazorthes, Yves; Mertens, Patrick; Blond, Serge; Geraud, G; Fabre, Nelly; Navez, Malou; Lucas, Christian; Dubois, Francois; Sol, Jean Christophe; Paquis, Philippe; Lemaire, Jean Jacques

    2010-04-01

    Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located <2 mm from the centres of effective contacts were: the mesencephalic grey substance (5/5), the red nucleus (4/5), the fascicle retroflexus (4/5), the fascicle longitudinal dorsal (3/5), the nucleus of ansa lenticularis (3/5), the fascicle longitudinal medial (1/5) and the thalamus superficialis medial (1/5). The contact coordinates (Wilcoxon test) and the structures (Fisher's exact test) were not significantly different between responders and non-responders. These findings suggest that failure of deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems. PMID:20237130

  10. Acute and long-term ventricular stimulation thresholds with a new, iridium oxide-coated electrode.

    PubMed

    Del Bufalo, A G; Schlaepfer, J; Fromer, M; Kappenberger, L

    1993-06-01

    Efforts have been made to design electrodes that significantly reduce not only the acute and chronic stimulation thresholds, but also attenuate the early peaking phenomenon and polarization. At two voltage levels (2.7 V and 5.4 V, respectively), we evaluated the right ventricular stimulation thresholds obtained with a new, iridium oxide-coated electrode in ten patients who received a VVI pacemaker. Measurements were made at implant and at multiple intervals for 1 year. Pulse width stimulation thresholds at implant were as follow: 0.04 +/- 0.008 msec at 2.7 V, 0.03 +/- 0.004 msec at 5.4 V; values at 2 weeks were 0.14 +/- 0.06 msec at 2.7 V, 0.07 +/- 0.025 msec at 5.4 V; values at 3 months were 0.09 +/- 0.03 msec at 2.7 V, 0.05 +/- 0.01 msec at 5.4 V; values at 1 year were 0.08 +/- 0.02 msec at 2.7 V, 0.04 +/- 0.01 msec at 5.4 V. The maximal increase of 0.11 +/- 0.05 msec occurred at 2.7 V, 2 weeks after implant. Our results indicate that this new electrode provides low acute and long-term stimulation thresholds, as well as an attenuated early peaking phenomenon, being able to stimulate safely at 2.7 V even early after implant. PMID:7686652

  11. Cortical evoked potentials from pallidal stimulation in patients with primary generalized dystonia.

    PubMed

    Tisch, Stephen; Rothwell, John C; Zrinzo, Ludvic; Bhatia, Kailash P; Hariz, Marwan; Limousin, Patricia

    2008-01-30

    Deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for primary generalized dystonia. However, the physiological mechanisms of improvement are not fully understood. Cortical activity in response to pallidal stimulation was recorded in 6 patients with primary generalized dystonia >6 months after bilateral GPi DBS. Scalp electroencephalogram was recorded using 60 surface electrodes during 10 Hz bipolar pallidal DBS at each electrode contact pair. Anatomical position of the electrode contacts in relation to the GPi, medial medullary lamina and globus pallidus externus (GPe) was determined from the postoperative stereotactic MRI. In all six patients an evoked potential (EP) was observed with average onset latency of 10.9 ms +/- 0.77, peak latency 26.6 ms +/- 1.6, distributed mainly over the ipsilateral hemisphere, maximal centrally. The mean amplitude of this potential was larger with stimulation in posteroventral GPi than in GPe (3.36 microV vs. 0.50 microV, P < 0.0001). The EP was absent in one patient-side, ipsilateral to a previous thalamotomy. Low frequency GPi stimulation produces an EP distributed centrally over the ipsilateral hemisphere. The latency and distribution of the EP are consistent with stimulation of pallidothalamic neurons projecting to the sensorimotor cortex. Because the EP is larger and more consistently present with stimulation of posteroventral GPi than GPe, it may provide a physiological tool to identify contacts within the optimal surgical target. PMID:18044698

  12. Subretinal electrode implantation in the P23H rat for chronic stimulations

    PubMed Central

    Salzmann, J; Linderholm, O P; Guyomard, J?L; Paques, M; Simonutti, M; Lecchi, M; Sommerhalder, J; Dubus, E; Pelizzone, M; Bertrand, D; Sahel, J; Renaud, P; Safran, A B; Picaud, S

    2006-01-01

    Background In age related macular degeneration and inherited dystrophies, preservation of retinal ganglion cells has been demonstrated. This finding has led to the development of various models of subretinal or epiretinal implant in order to restore vision. This study addresses the development of a polyimide subretinal electrode platform in the dystrophic P23H rat in vivo. Methods A technique was developed for implanting a subretinal electrode into the subretinal space and stabilising the distal extremity of the cabling on the rat cranium in order to allow future electrical stimulations of the retina. Results In vivo imaging of the retina with the scanning laser ophthalmoscope demonstrated reabsorption of the surgically induced retinal detachment and the absence of major tissue reactions. These in vivo observations were confirmed by retinal histology. The extraocular fixation system on the rat cranium was effective in stabilising the distal connector for in vivo stimulation. Conclusion This study demonstrates that a retinal implant can be introduced into the subretinal space of a dystrophic rat with a stable external connection for repeatable electrical measurements and stimulation. This in vivo model should therefore allow us to evaluate the safety and efficacy of electrical stimulations on dystrophic retina. PMID:16754649

  13. Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

    PubMed

    Segar, David J; Chodakiewitz, Yosef G; Torabi, Radmehr; Cosgrove, G Rees

    2015-06-01

    Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation. PMID:26030700

  14. 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; Krger, 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. PMID:22450824

  15. 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.

  16. Measures to Evaluate the Effects of DBS on Speech Production

    PubMed Central

    Weismer, Gary; Yunusova, Yana; Bunton, Kate

    2011-01-01

    The purpose of this paper is to review and evaluate measures of speech production that could be used to document effects of Deep Brain Stimulation (DBS) on speech performance, especially in persons with Parkinson disease (PD). A small set of evaluative criteria for these measures is presented first, followed by consideration of several speech physiology and speech acoustic measures that have been studied frequently and reported on in the literature on normal speech production, and speech production affected by neuromotor disorders (dysarthria). Each measure is reviewed and evaluated against the evaluative criteria. Embedded within this review and evaluation is a presentation of new data relating speech motions to speech intelligibility measures in speakers with PD, amyotrophic lateral sclerosis (ALS), and control speakers (CS). These data are used to support the conclusion that at the present time the slope of second formant transitions (F2 slope), an acoustic measure, is well suited to make inferences to speech motion and to predict speech intelligibility. The use of other measures should not be ruled out, however, and we encourage further development of evaluative criteria for speech measures designed to probe the effects of DBS or any treatment with potential effects on speech production and communication skills. PMID:24932066

  17. 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

  18. Evaluation of a suture electrode for direct bladder stimulation in a lower motor neuron lesioned animal model.

    PubMed

    Walter, J S; Wheeler, J S; Cai, W; King, W W; Wurster, R D

    1999-06-01

    The purpose of this study was to evaluate a "suture" type electrode for direct bladder stimulation in an animal model of a lower motor neuron lesion. During an initial surgery, five male cats were instrumented under anesthesia using multistranded, 316 LVM, stainless-steel, wire electrodes implanted on the bladder wall serosa above the trigone area. Electrodes were constructed with a needle attached to the end that was removed after suturing the electrode in place. Additional instrumentation included urinary bladder catheters (tubes) for pressure recording and filling, and hook type electrodes for leg and pelvic floor electromyography recording. Chronic bladder filling and stimulation studies were conducted in tethered animals three to four weeks following surgery. To test these electrodes in a spinal cord injury model, a lower motor neuron lesion was performed including the sacral cord and complete nerve roots at L6 and below. These animals were evaluated during weeks 3 and 10 after injury. Direct bladder stimulation induced active contractions and voiding both before and after spinal cord injury. Effective stimulation parameters consisted of 40 pulses per s, 300 micros to 1 ms pulse duration, a stimulation period from 3 to 4 s, and a stimulation current from 10 to 40 mA. Fluoroscopy revealed an open membranous urethra during stimulation and following stimulation. A small diameter penile urethra was observed to limit flow. Postmortem evaluation of the suture electrode revealed no abnormalities such as corrosion, migration into the bladder lumen or displacement. These findings indicate that suture electrodes are suitable and effective for short-term implantation in the lower motor neuron animal model. PMID:10391586

  19. Thalamic stimulation and functional magnetic resonance imaging: localization of cortical and subcortical activation with implanted electrodes. Technical note.

    PubMed

    Rezai, A R; Lozano, A M; Crawley, A P; Joy, M L; Davis, K D; Kwan, C L; Dostrovsky, J O; Tasker, R R; Mikulis, D J

    1999-03-01

    The utility of functional magnetic resonance (fMR) imaging in patients with implanted thalamic electrodes has not yet been determined. The aim of this study was to establish the safety of performing fMR imaging in patients with thalamic deep brain stimulators and to determine the value of fMR imaging in detecting cortical and subcortical activity during stimulation. Functional MR imaging was performed in three patients suffering from chronic pain and two patients with essential tremor. Two of the three patients with pain had undergone electrode implantation in the thalamic sensory ventralis caudalis (Vc) nucleus and the other had undergone electrode implantation in both the Vc and the periventricular gray (PVG) matter. Patients with tremor underwent electrode implantation in the ventralis intermedius (Vim) nucleus. Functional MR imaging was performed during stimulation by using a pulse generator connected to a transcutaneous extension lead. Clinically, Vc stimulation evoked paresthesias in the contralateral body, PVG stimulation evoked a sensation of diffuse internal body warmth, and Vim stimulation caused tremor arrest. Functional images were acquired using a 1.5-tesla MR imaging system. The Vc stimulation at intensities provoking paresthesias resulted in activation of the primary somatosensory cortex (SI). Stimulation at subthreshold intensities failed to activate the SI. Additional stimulation-coupled activation was observed in the thalamus, the secondary somatosensory cortex (SII), and the insula. In contrast, stimulation of the PVG electrode did not evoke paresthesias or activate the SI, but resulted in medial thalamic and cingulate cortex activation. Stimulation in the Vim resulted in thalamic, basal ganglia, and SI activation. An evaluation of the safety of the procedure indicated that significant current could be induced within the electrode if a faulty connecting cable (defective insulation) came in contact with the patient. Simple precautions, such as inspection of wires for fraying and prevention of their contact with the patient, enabled the procedure to be conducted safely. Clinical safety was further corroborated by performing 86 MR studies in patients in whom electrodes had been implanted with no adverse clinical effects. This is the first report of the use of fMR imaging during stimulation with implanted thalamic electrodes. The authors' findings demonstrate that fMR imaging can safely detect the activation of cortical and subcortical neuronal pathways during stimulation and that stimulation does not interfere with imaging. This approach offers great potential for understanding the mechanisms of action of deep brain stimulation and those underlying pain and tremor generation. PMID:10067936

  20. DBS pay television: Picture signal scrambling

    NASA Astrophysics Data System (ADS)

    Knee, M. J.

    1985-10-01

    Picture signal scrambling methods suitable for a direct broadcast by satellite DBS MAC pay television channel are described. They use a technique known as rotation scrambling, which is shown to meet the likely requirements for picture quality, security against piracy, scrambling effectiveness and cost. The methods have been tested using experimental equipment and the results have led to an agreement within the EBU to incorporate them into the MAC specification.

  1. 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.

  2. Microthalamotomy effect during deep brain stimulation: potential involvement of adenosine and glutamate efflux.

    PubMed

    Chang, Su-Youne; Shon, Young Min; Agnesi, Filippo; Lee, Kendall H

    2009-01-01

    Deep brain stimulation (DBS) of the thalamus is widely used in humans to treat essential tremor and tremor dominant Parkinson's disease. After DBS lead implantation, tremor is often reduced even without electrical stimulation. Often called "microthalamotomy" effect, the exact mechanism is unknown, although it is presumed to be due to micro lesioning. Here, we tested whether microthalamotomy effect may, in fact, be mediated via release of neurotransmitters adenosine and glutamate, using fast scan cyclic voltammetry (FSCV) and amperometry, respectively. Implantation of microelectrodes into the ventrolateral (VL) thalamus of the rat resulted in transient rise in adenosine and glutamate level from mechanical stimulation. Similarly, high frequency stimulation (100 - 130 Hz) of the VL thalamus also resulted in adenosine and glutamate release. These results suggest that glutamate and adenosine release may be an important and unappreciated mechanism whereby mechanical stimulation via electrode implantation procedure may achieve the microthalamotomy effect. PMID:19964296

  3. Microthalamotomy effect during Deep Brain Stimulation: Potential Involvement of Adenosine and Glutamate Efflux

    PubMed Central

    Chang, Su-Youne; Shon, Young Min; Agnesi, Filippo; Lee, Kendall H.

    2010-01-01

    Deep brain stimulation (DBS) of the thalamus is widely used in humans to treat essential tremor and tremor dominant Parkinsons disease. After DBS lead implantation, tremor is often reduced even without electrical stimulation. Often called microthalamotomy effect, the exact mechanism is unknown, although it is presumed to be due to micro lesioning. Here, we tested whether microthalamotomy effect may, in fact, be mediated via release of neurotransmitters adenosine and glutamate, using fast scan cyclic voltammetry (FSCV) and amperometry, respectively. Implantation of microelectrodes into the ventrolateral (VL) thalamus of the rat resulted in transient rise in adenosine and glutamate level from mechanical stimulation. Similarly, high frequency stimulation (100 130 Hz) of the VL thalamus also resulted in adenosine and glutamate release. These results suggest that glutamate and adenosine release may be an important and unappreciated mechanism whereby mechanical stimulation via electrode implantation procedure may achieve the microthalamotomy effect. PMID:19964296

  4. Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor

    PubMed Central

    Dembek, Till A.; Becker, Johannes; Raethjen, Jan; Hartinger, Mariam; Meister, Ingo G.; Runge, Matthias; Maarouf, Mohammad; Fink, Gereon R.; Timmermann, Lars

    2014-01-01

    Objective: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). Methods: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. Results: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a noncurrent-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. Conclusion: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. Classification of evidence: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control. PMID:24443448

  5. Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial

    PubMed Central

    Weintraub, Daniel; Duda, John E; Carlson, Kimberly; Luo, Ping; Sagher, Oren; Stern, Matthew; Follett, Kenneth A; Reda, Domenic; Weaver, Frances M

    2015-01-01

    Background The risk of suicide behaviours post–deep brain stimulation (DBS) surgery in Parkinson's disease (PD) remains controversial. We assessed if suicide ideation and behaviours are more common in PD patients (1) randomised to DBS surgery versus best medical therapy (BMT); and (2) randomised to subthalamic nucleus (STN) versus globus pallidus interna (GPi) DBS surgery. Methods In Phase 1 of the Veterans Affairs CSP 468 study, 255 PD patients were randomised to DBS surgery (n=121) or 6 months of BMT (n=134). For Phase 2, a total of 299 patients were randomised to STN (n=147) or GPi (n=152) DBS surgery. Patients were assessed serially with the Unified Parkinson's Disease Rating Scale Part I depression item, which queries for suicide ideation; additionally, both suicide behaviour adverse event data and proxy symptoms of increased suicide risk from the Parkinson's Disease Questionnaire (PDQ-39) and the Short Form Health Survey (SF-36) were collected. Results In Phase 1, no suicide behaviours were reported, and new-onset suicide ideation was rare (1.9% for DBS vs 0.9% for BMT; Fisher's exact p=0.61). Proxy symptoms of relevance to suicide ideation were similar in the two groups. Rates of suicide ideation at 6 months were similar for patients randomised to STN versus GPi DBS (1.5% vs 0.7%; Fisher's exact p=0.61), but several proxy symptoms were worse in the STN group. Conclusions Results from the randomised, controlled phase of a DBS surgery study in PD patients do not support a direct association between DBS surgery and an increased risk for suicide ideation and behaviours. PMID:23667214

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

    PubMed

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

    2015-08-01

    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. PMID:26737885

  7. Selective stimulation of the human femoral nerve with a flat interface nerve electrode

    NASA Astrophysics Data System (ADS)

    Schiefer, M. A.; Polasek, K. H.; Triolo, R. J.; Pinault, G. C. J.; Tyler, D. J.

    2010-04-01

    In humans, we tested the hypothesis that a flat interface nerve electrode (FINE) placed around the femoral nerve trunk can selectively stimulate each muscle the nerve innervates. In a series of intraoperative trials during routine vascular surgeries, an eight-contact FINE was placed around the femoral nerve between the inguinal ligament and the first nerve branching point. The capability of the FINE to selectively recruit muscles innervated by the femoral nerve was assessed with electromyograms (EMGs) of the twitch responses to electrical stimulation. At least four of the six muscles innervated by the femoral nerve were independently and selectively recruited in all subjects. Of these, at least one muscle was a hip flexor and at least two were knee extensors. Results from the intraoperative experiments were used to estimate the potential for the electrode to restore knee extension and hip flexion through functional electrical stimulation. Normalized EMGs and biomechanical simulations were used to estimate joint moments and functional efficacy. Estimated knee extension moments exceed the threshold required for the sit-to-stand transition.

  8. Postoperative delirium in Parkinson's disease patients following deep brain stimulation surgery.

    PubMed

    Carlson, Jonathan D; Neumiller, Joshua J; Swain, Lindy D W; Mark, Jamie; McLeod, Pam; Hirschauer, Jeff

    2014-07-01

    Deep brain stimulation (DBS) surgery is an effective treatment for patients with advanced Parkinson's disease. Delirium in hospitalized Parkinson's disease patients is common and often leads to prolonged hospital stays. This study reports on the incidence and etiology of postoperative delirium following DBS surgery. Patients (n=59) with advanced Parkinson's disease underwent bilateral (n=56) or unilateral (n=3) DBS electrode implant surgery, followed 1 week later with surgical placement of DBS generators. The development of delirium during either hospital stay was evaluated retrospectively from the hospital chart. Potential causes of delirium were evaluated, including history of delirium, opiate equivalents, medication administration delays and missed doses during hospitalization, and Parkinson's disease duration. Delirium following implantation of DBS electrodes was common (22% of patients). It was less commonly associated with generator placement (10%). A history of delirium, age, and disease duration were positive predictors of delirium. Opiate equivalent doses were negatively correlated with delirium. Missed Parkinson's medication doses (53% of patients) and delayed administration (81% of patients) were common, and had a slight relation with delirium. Delirium was not related to complexity of medication regimen or use of dementia medications. Despite the presence of delirium most patients still only required a single night in the hospital post-surgery (67%). Prolonged hospital stay was due not only to delirium but also severe off states and other medical issues. Recognition and expectant management of delirium is best accomplished in a multidisciplinary setting, including the patient's family and nursing, pharmacy and neurological surgery staff. PMID:24518269

  9. 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-Ray Spectroscopy (EDS), and Electron Spectroscopy for Chemical Analysis (ESCA). Representative tissue/electrode interfaces were created through subcutaneous implantation and harvest from Balb/C mice after 7, 28 and 56 days. The recovered, formalin preserved conductive implant/tissue specimens were examined by Electrical Impedance Spectroscopy (EIS) over the range from 0.1 Hz to 100,000 Hz, in Bode plot and Nyquist plot formats. After EIS the implants were extracted from the tissue for surface examination by SEM and the separated tissue capsules were evaluated by histological examination in hematoxylin and eosin (H&E)-stained light microscopic thin sections. The differential findings were that the RFGDT PyC and Ta implants had significantly increased interface resistance and capacitance over their sterilized-only controls, correlating with more flattened cellular layers retained on the RFGDT specimens. The cpTi specimens, earlier identified as promoting hard tissue-to-surface integration in dental implants, showed only marginal improvements in soft tissue attachment following RFGDT. These experimental findings were confirmed through equivalent circuit modeling by the conversion from a standard Randles model with constant phase elements, which described the pre-implant materials, to a modified Randles model with additional resistance and capacitance to describe the implants with well-integrated surface coatings. Future work with RFGDT-modified electrode materials must include actual signal acquisition/stimulation trials in implant host tissues, to assess possible improvements in electrical energy-transfer efficiency and battery lifetime extensions.

  10. 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.

  11. Iridium oxide deposited by pulsed dc-sputtering for stimulation electrodes

    NASA Astrophysics Data System (ADS)

    van Ooyen, A.; Topalov, G.; Ganske, G.; Mokwa, W.; Schnakenberg, U.

    2009-07-01

    A pulsed-dc reactive sputtering technique was used for iridium oxide thin-film deposition. Pulsing frequency and oxygen flow were varied over several deposition cycles, regarding stimulation electrode applications. Surface and electrochemical analysis were performed for deposition evaluation. The results show the influence of the oxygen flow to the morphology and the electrochemical properties of the reactively sputtered films. Optimal surface structure and electrochemical properties for films deposited at 0.016 mbar working pressure, 100 kHz pulse frequency and 1 s pulsewidth can be achieved at oxygen flows around 8 to 10 sccm.

  12. Efficient search and fit methods to find nerve stimulation parameters for multi-contact electrodes.

    PubMed

    Freeberg, Max J; Schiefer, Matthew A; Triolo, Ronald J

    2011-01-01

    This paper describes a method to efficiently sample EMG recruitment space over a wide range of pulse amplitude (PA) and pulse width (PW). A gradient based search method is developed to find high information areas of a recruitment surface. This search method is first examined in the context of simulated EMG recruitment data and its ability to sample and subsequently fit Gompertz-Function-inspired surfaces to it. The search method is then used to determine parameters when stimulating through an 8 contact flat interface nerve electrode (FINE). The recorded EMG recruitment data are then used to validate the Gompertz surface fitting method as well as the search method. PMID:22256009

  13. 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.

  14. 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

  15. Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders.

    PubMed

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2015-10-01

    Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

  16. Deep brain stimulation as a tool for improving cognitive functioning in Alzheimer's dementia: a systematic review.

    PubMed

    Hardenacke, Katja; Shubina, Elena; Bührle, Christian Philipp; Zapf, Alexandra; Lenartz, Doris; Klosterkötter, Joachim; Visser-Vandewalle, Veerle; Kuhn, Jens

    2013-01-01

    Deep brain stimulation (DBS) is an established, in selected cases therapeutically effective, non-lesional treatment method delivering current rectangular pulses into dysfunctional brain structures via chronically implanted stimulation electrodes. DBS is a recognized method applied in movement disorders and is increasingly evaluated as a possible therapeutic option for psychiatric diseases such as refractory obsessive-compulsive disorders, Gilles de la Tourette syndrome, major depression, and substance-related addiction. Latest research indicates that DBS may be a method for improving cognitive functions in Alzheimer's dementia (AD). Translational data in healthy and AD animals appear to support this notion. Nevertheless, many aspects remain unclear, particularly with regard to the optimal target structure. The objective of this review is to present a systematic overview regarding published research on DBS and cognitive functioning in animal and human studies as well as to provide a systematic overview of the feasibility and efficacy of the treatment. We describe three studies investigating the effects of DBS in patients with dementia, using either the fornix or the nucleus basalis of Meynert (NBM) as a target. In total, we identified 25 animal studies with 10 brain structures being targeted: fornix, NBM, anterior caudate nucleus, dorsal striatum, anterior thalamic nucleus, midline thalamic nuclei, central thalamus, lateral hypothalamus, hippocampus (entorhinal cortex, perforant path), and amygdala. Considering the wide and diverse spectrum of targets, we add to this review a supposition about possible underlying mechanisms of operation and recommendations for further research. PMID:24363647

  17. 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.

  18. High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson's disease

    PubMed Central

    Whitmer, Diane; de Solages, Camille; Hill, Bruce; Yu, Hong; Henderson, Jaimie M.; Bronte-Stewart, Helen

    2012-01-01

    Parkinson's disease (PD) is marked by excessive synchronous activity in the beta (835 Hz) band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS) within the subthalamic nucleus (STN) region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and is of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI) to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway (HDP) between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05). Cortical signals over the estimated origin of the HDP also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially-specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network. PMID:22675296

  19. The anteromedial GPi as a new target for deep brain stimulation in obsessive compulsive disorder.

    PubMed

    Nair, Girish; Evans, Andrew; Bear, Renee E; Velakoulis, Dennis; Bittar, Richard G

    2014-05-01

    Deep brain stimulation (DBS) is now well established in the treatment of intractable movement disorders. Over the past decade the clinical applications have expanded into the realm of psychosurgery, including depression and obsessive compulsive disorder (OCD). The optimal targets for electrode placement in psychosurgery remain unclear, with numerous anatomical targets reported for the treatment of OCD. We present four patients with Tourette's syndrome and prominent features of OCD who underwent DBS of the anteromedial globus pallidus internus (GPi) to treat their movement disorder. Their pre-operative and post-operative OCD symptoms were compared, and responded dramatically to surgery. On the basis of these results, we propose the anteromedial (limbic) GPi as a potential surgical target for the treatment of OCD, and furnish data supporting its further investigation as a DBS target for the treatment of psychiatric conditions. PMID:24524950

  20. 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

  1. 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.

  2. 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. PMID:26471198

  3. Lateralized effect of pallidal stimulation on self-mutilation in Lesch-Nyhan disease.

    PubMed

    Abel, Taylor J; Dalm, Brian D; Grossbach, Andrew J; Jackson, Adam W; Thomsen, Teri; Greenlee, Jeremy D W

    2014-12-01

    Lesch-Nyhan disease (LND) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. This syndrome is characterized by hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia. The authors describe the case of a 15-year-old boy who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. This case is the first reported instance of LND treated with DBS in which the stimulation was interrupted and the self-mutilation returned in a lateralized fashion. The findings indicate that the neurobehavioral aspect of LND is lateralized and that contralateral GPi stimulation is responsible for lateralized improvement in self-injurious behavior. PMID:25303157

  4. 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.

  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. Reliability of percutaneous intramuscular electrodes for upper extremity functional neuromuscular stimulation in adolescents with C5 tetraplegia.

    PubMed

    Smith, B T; Betz, R R; Mulcahey, M J; Triolo, R J

    1994-09-01

    Chronically indwelling percutaneous intramuscular electrodes were implanted in the upper extremity muscles of five adolescents with C5 or C5-6 tetraplegia in an effort to provide lateral and palmar prehension using the neuroprosthetic system designed by Case Western Reserve University. The responses from 177 electrodes were evaluated at 3-month intervals and included measurements of electrical impedance and an assessment of recruitment properties. Electrode failures were categorized as breakage, an altered stimulated response or adverse sensation during stimulation. Survival probabilities were generated for all electrodes, each muscle group, the volar and dorsal exit sites, intrinsic and extrinsic muscles, and according to the subjects' time postinjury. The overall probability of an electrode surviving to 6 months was 0.75 and the 1 year survival probability was 0.56. Among muscle groups, the finger extensor and thumb adductor electrodes had the highest proportion of failures and the poorest survival likelihoods within the first year after implant. According to the Breslow test, significantly smaller survival chances were predicted for electrodes exiting dorsally and for the newly-injured adolescents (< 1 year postinjury). The cumulative survival likelihoods of this study are smaller than those reported in adult applications using the same electrode design. Factors that may account for the disparate results are discussed. PMID:8085926

  7. Comparison of VIM and STN DBS for Parkinsonian Resting and Postural/Action Tremor

    PubMed Central

    Parihar, Raminder; Alterman, Ron; Papavassiliou, Efstathios; Tarsy, Daniel; Shih, Ludy C.

    2015-01-01

    Background Resting tremor is common in Parkinsons disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD. Methods We carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinsons Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest. Results A total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up. Discussion This study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor. PMID:26196027

  8. [Bowstringing as a complication of deep brain stimulation].

    PubMed

    Castro Bouzas, Daniel; Serramito Garca, Ramn; Relova Quinteiro, Jos Luis; Castro Garca, Alfonso; Ares Pensado, Begoa; Sesar Ignacio, Angel; Gelabert-Gonzlez, Miguel

    2013-01-01

    Deep brain stimulation (DBS) is an established surgical therapy for intractable movement disorders, such as Parkinson's disease, essential tremor and dystonia. As the number of treated patients has increased rapidly, new sets of problems about complications of DBS have arisen. Bowstringing is defined as abnormal tethering of leads between the pulse generators and stimulating electrode, associated with pain and contracture of the neck over the extension cable. We report the case of a 56-year-old woman with a history of advanced Parkinson's disease who had been treated by implantation of a bilateral, subthalamic nucleus, deep brain stimulator. A car accident caused the rupture of the right electrode, which was replaced. Six months after the replacement the patient presented disabling pain and tension in the neck where deep brain extension cables were located. A cervical incision was performed to excise scar tissue. Bowstringing is a rare complication of DBS and although patients sometimes report discomfort and tension in the cervical region, surgical procedures are not normally required. PMID:23246336

  9. Streamlining deep brain stimulation surgery by reversing the staging order.

    PubMed

    van Horne, Craig G; Vaughan, Scott W; Massari, Carla; Bennett, Michael; Asfahani, Wissam S Z; Quintero, Jorge E; Gerhardt, Greg A

    2015-05-01

    Deep brain stimulation (DBS) is approved for several clinical indications; however, the sequencing of DBS surgery and the timeline for implementing stimulation therapy are not standardized. In over 140 cases so far, the authors have reversed the sequencing for staged implantation of DBS systems that was conducive to minimizing patient anxiety and discomfort while providing the opportunity to shorten the time between implantation and programming for therapeutic management of symptoms. Stage I was performed with the patient under general anesthesia and consisted of implantation of the pulse generator and lead extensions and placement of the bur holes. Stage II was completed 1-7 days later, using only local anesthesia, and included stereotactic frame-based microelectrode recordings, semi-microstimulation and macrostimulation, and testing and placement of the stimulating electrodes. Stage I lasted approximately 90 minutes, whereas Stage II lasted approximately 230 minutes. All patients tolerated the procedures and received a complete implanted system. Deep brain stimulation therapy was typically initiated on the same day as lead implantation. When sequencing was reversed and bur holes were placed during the first stage while a patient was under general anesthesia, the patient was able to tolerate the second awake stage and was able to begin stimulation therapy within 48 hours of the second stage. PMID:25748305

  10. Pacing electrode selection in a quadripolar left heart lead determines presence or absence of phrenic nerve stimulation.

    PubMed

    Thibault, Bernard; Karst, Edward; Ryu, Kyungmoo; Paiement, Patrice; Farazi, Taraneh G

    2010-05-01

    A 60-year-old ischaemic patient presented for routine cardiac resynchronization therapy (CRT)-D implantation. An investigational quadripolar left ventricular lead was placed in the posterolateral vein. Phrenic nerve stimulation (PNS) was observed, but it occurred during pacing from only one of the four electrodes. A lead with multiple pacing electrodes is a potential alternative to physical adjustment of the lead or discontinuing CRT when PNS occurs. PMID:20080902

  11. 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.

  12. Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve

    NASA Astrophysics Data System (ADS)

    Fisher, L. E.; Tyler, D. J.; Anderson, J. S.; Triolo, R. J.

    2009-08-01

    This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 N m. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 N m in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications.

  13. Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve

    PubMed Central

    Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

    2010-01-01

    This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 Nm. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 Nm in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications. PMID:19602729

  14. Deep Brain Stimulation as a Tool for Improving Cognitive Functioning in Alzheimer’s Dementia: A Systematic Review

    PubMed Central

    Hardenacke, Katja; Shubina, Elena; Bührle, Christian Philipp; Zapf, Alexandra; Lenartz, Doris; Klosterkötter, Joachim; Visser-Vandewalle, Veerle; Kuhn, Jens

    2013-01-01

    Deep brain stimulation (DBS) is an established, in selected cases therapeutically effective, non-lesional treatment method delivering current rectangular pulses into dysfunctional brain structures via chronically implanted stimulation electrodes. DBS is a recognized method applied in movement disorders and is increasingly evaluated as a possible therapeutic option for psychiatric diseases such as refractory obsessive-compulsive disorders, Gilles de la Tourette syndrome, major depression, and substance-related addiction. Latest research indicates that DBS may be a method for improving cognitive functions in Alzheimer’s dementia (AD). Translational data in healthy and AD animals appear to support this notion. Nevertheless, many aspects remain unclear, particularly with regard to the optimal target structure. The objective of this review is to present a systematic overview regarding published research on DBS and cognitive functioning in animal and human studies as well as to provide a systematic overview of the feasibility and efficacy of the treatment. We describe three studies investigating the effects of DBS in patients with dementia, using either the fornix or the nucleus basalis of Meynert (NBM) as a target. In total, we identified 25 animal studies with 10 brain structures being targeted: fornix, NBM, anterior caudate nucleus, dorsal striatum, anterior thalamic nucleus, midline thalamic nuclei, central thalamus, lateral hypothalamus, hippocampus (entorhinal cortex, perforant path), and amygdala. Considering the wide and diverse spectrum of targets, we add to this review a supposition about possible underlying mechanisms of operation and recommendations for further research. PMID:24363647

  15. 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.

  16. 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. PMID:25529183

  17. Using MDEFT MRI Sequences to Target the GPi in DBS Surgery

    PubMed Central

    Fichtner, Jens; Debove, Ines; Lachenmayer, Lenard; Schpbach, Michael; Oertel, Markus Florian; Wiest, Roland; Pollo, Claudio

    2015-01-01

    Objective Recent advances in different MRI sequences have enabled direct visualization and targeting of the Globus pallidus internus (GPi) for DBS surgery. Modified Driven Equilibrium Fourier Transform (MDEFT) MRI sequences provide high spatial resolution and an excellent contrast of the basal ganglia with low distortion. In this study, we investigate if MDEFT sequences yield accurate and reliable targeting of the GPi and compare direct targeting based on MDEFT sequences with atlas-based targeting. Methods 13 consecutive patients considered for bilateral GPi-DBS for dystonia or PD were included in this study. Preoperative targeting of the GPi was performed visually based on MDEFT sequences as well as by using standard atlas coordinates. Postoperative CT imaging was performed to calculate the location of the implanted leads as well as the active electrode(s). The coordinates of both visual and atlas based targets were compared. The stereotactic coordinates of the lead and active electrode(s) were calculated and projected on the segmented GPi. Results On MDEFT sequences the GPi was well demarcated in most patients. Compared to atlas-based planning the mean target coordinates were located significantly more posterior. Subgroup analysis showed a significant difference in the lateral coordinate between dystonia (LAT = 19.33 0.90) and PD patients (LAT = 20.67 1.69). Projected on the segmented preoperative GPi the active contacts of the DBS electrode in both dystonia and PD patients were located in the inferior and posterior part of the structure corresponding to the motor part of the GPi. Conclusions MDEFT MRI sequences provide high spatial resolution and an excellent contrast enabling precise identification and direct visual targeting of the GPi. Compared to atlas-based targeting, it resulted in a significantly different mean location of our target. Furthermore, we observed a significant variability of the target among the PD and dystonia subpopulation suggesting accurate targeting for each individual patient. PMID:26366574

  18. Probabilistic Modeling of Selective Stimulation of the Human Sciatic Nerve with a Flat Interface Nerve Electrode

    PubMed Central

    Schiefer, Matthew A.; Tyler, Dustin J.; Triolo, Ronald J.

    2012-01-01

    Ankle control is critical to both standing balance and efficient walking. This hypothesis presented in this paper is that a Flat Interface Nerve Electrode (FINE) placed around the sciatic nerve with a fixed number of contacts at predetermined locations and without a priori knowledge of the nerves underlying neuroanatomy can selectively control each ankle motion. Models of the human sciatic nerve surrounded by a FINE of varying size were created and used to calculate the probability of selective activation of axons within any arbitrarily designated, contiguous group of fascicles. Simulations support the hypothesis and suggest that currently available implantable technology cannot selectively recruit each target plantar flexor individually but can restore plantar flexion or dorsiflexion from a site on the sciatic nerve without spillover to antagonists. Successful activation of individual ankle muscles in 90% of the population can be achieved by utilizing bipolar stimulation and/or by using a cuff with at least 20 contacts. PMID:22222951

  19. 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. PMID:17429407

  20. 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.

  1. Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS

    PubMed Central

    2012-01-01

    The field of non-pharmacological therapies for treatment resistant depression (TRD) is rapidly evolving and new somatic therapies are valuable options for patients who have failed numerous other treatments. A major challenge for clinicians (and patients alike) is how to integrate the results from published clinical trials in the clinical decision-making process. We reviewed the literature for articles reporting results for clinical trials in particular efficacy data, contraindications and side effects of somatic therapies including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS) and deep brain stimulation (DBS). Each of these devices has an indication for patients with different level of treatment resistance, based on acuteness of illness, likelihood of response, costs and associated risks. ECT is widely available and its effects are relatively rapid in severe TRD, but its cognitive adverse effects may be cumbersome. TMS is safe and well tolerated, and it has been approved by FDA for adults who have failed to respond to one antidepressant, but its use in TRD is still controversial as it is not supported by rigorous double-blind randomized clinical trials. The options requiring surgical approach are VNS and DBS. VNS has been FDA-approved for TRD, however it is not indicated for management of acute illness. DBS for TRD is still an experimental area of investigation and double-blind clinical trials are underway. PMID:22901565

  2. 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.

  3. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... make a determination of whether its signal level(s) will exceed the EPFD limit at any DBS customer of record sites. To assist in making this determination, the MVDDS provider can use the EPFD contour model... operations, the MVDDS licensee shall provide the following information to the DBS licensee(s): (i)...

  4. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... make a determination of whether its signal level(s) will exceed the EPFD limit at any DBS customer of record sites. To assist in making this determination, the MVDDS provider can use the EPFD contour model... operations, the MVDDS licensee shall provide the following information to the DBS licensee(s): (i)...

  5. 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)?, 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. PMID:20600170

  6. Deep Brain Stimulation for Parkinson's Disease

    MedlinePLUS

    ... Enhancing Diversity Find People About NINDS NINDS Deep Brain Stimulation for Parkinson's Disease Information Page Condensed from ... and Information Publicaciones en Español What is Deep Brain Stimulation for Parkinson's Disease? Deep brain stimulation (DBS) ...

  7. DBS -- An rlogin multiplexer and output logger for DA systems

    SciTech Connect

    Oleynik, G.; Appleton, L.; Udumula, L.; Votava, M.

    1994-04-01

    DART Bootstrap Services (dbs) is the first component of run-control for the DART Data Acquisition system -- the DA for the 96` round of experiments at Fermilab -- though it has potential usefulness as a powerful tool in other distributed applications. dbs is an rlogin session multiplexer. It allows a user, running a single program, to start up any number of remote login sessions, feed shell commands to them, and collect their output into a single (or multiple) log files (a server keeps the sessions open and collects their output). From this program, any session can be attached to interactively so it appears just like an rlogin session -- dbs becomes transparent. When finished with this interactive mode, the user can escape back to dbs and attach to a different session if so desired. Among many other useful features, dbs supplies a mechanism for cleanup (deletion) of all processes created under a session, allowing a fresh start.

  8. 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. PMID:26037016

  9. Continuous stimulation of the pedunculopontine tegmental nucleus at 40 Hz affects preparative and executive control in a delayed sensorimotor task and reduces rotational movements induced by apomorphine in the 6-OHDA parkinsonian rat.

    PubMed

    Capozzo, Annamaria; Vitale, Flora; Mattei, Claudia; Mazzone, Paolo; Scarnati, Eugenio

    2014-09-01

    The pedunculopontine tegmental nucleus (PPTg) relays basal ganglia signals to the thalamus, lower brainstem and spinal cord. Using the 6-hydroxydopamine (6-OHDA) rat model of parkinsonism, we investigated whether deep brain stimulation (DBS) of the PPTg (40 Hz, 60 μs, 200-400 μA) may influence the preparative and executive phases in a conditioned behavioural task, and the motor asymmetries induced by apomorphine. In the conditioned task, rats had to press two levers according to a fixed delay paradigm. The 6-OHDA lesion was placed in the right medial forebrain bundle, i.e. contralaterally to the preferred forepaw used by rats to press levers in the adopted task. The stimulating electrode was implanted in the right PPTg, i.e. contralateral to left side, which was expected to be most affected. The lesion significantly reduced correct responses from 63.4% to 16.6%. PPTg-DBS effects were episodic; however, when rats successfully performed in the task (18.9%), reaction time (468.8 ± 36.5 ms) was significantly increased (589.9 ± 45.9 ms), but not improved by PPTg-DBS (646.7 ± 33.8 ms). Movement time was significantly increased following the lesion (649.2 ± 42.6 ms vs. 810.9 ± 53.0 ms), but significantly reduced by PPTg-DBS (820.4 ± 39.4 ms) compared to sham PPTg-DBS (979.8 ± 47.6 ms). In a second group of lesioned rats, rotations induced by apomorphine were significantly reduced by PPTg-DBS compared to sham PPTg-DBS (12.2 ± 0.6 vs. 9.5 ± 0.4 mean turns/min). Thus, it appears that specific aspects of motor deficits in 6-OHDA-lesioned rats may be modulated by PPTg-DBS. PMID:24959863

  10. 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…

  11. Matrix-addressable, active electrode arrays for neural stimulation using organic semiconductors-cytotoxicity and pilot experiments in vivo.

    PubMed

    Feili, Dara; Schuettler, Martin; Stieglitz, Thomas

    2008-03-01

    Organic field effect transistors can be integrated into micromachined polyimide-based neural stimulation electrode arrays in order to build active switching matrices. With this approach, a matrix of N x M electrode contacts requires only N + M interconnects to a stimulator when active switching elements are used instead of N x M interconnects. In this paper, we demonstrated that pentacene-based organic field effect transistors (OFETs) can be used to drive stimulation currents through neural electrodes in a physiological-like environment. In order to prove the general applicability as an implant material, the cytotoxicity of pentacene was evaluated with respect to potential effects on cell viability. The results of these tests indicate that extracts from pentacene inhibit neither proliferation nor metabolism of the tested mouse fibroblasts. However, some effect on cell spreading was observed when cells were in direct contact to pentacene for 48 h. In pilot experiments it was demonstrated for the very first time that pentacene transistors can be used as switching elements, acting as voltage-controlled current sources, capable of driving currents suitable for electrical stimulation of a peripheral nerve via a tripolar cuff electrode. PMID:18310812

  12. Nucleus Accumbens Deep Brain Stimulation Results in Insula and Prefrontal Activation: A Large Animal fMRI Study

    PubMed Central

    Knight, Emily J.; Min, Hoon-Ki; Hwang, Sun-Chul; Marsh, Michael P.; Paek, Seungleal; Kim, Inyong; Felmlee, Joel P.; Abulseoud, Osama A.; Bennet, Kevin E.; Frye, Mark A.; Lee, Kendall H.

    2013-01-01

    Background Deep Brain Stimulation (DBS) of the nucleus accumbens (NAc) has previously been investigated clinically for the treatment of several psychiatric conditions, including obsessive-compulsive disorder and treatment resistant depression. However, the mechanism underlying the therapeutic benefit of DBS, including the brain areas that are activated, remains largely unknown. Here, we utilized 3.0 T functional Magnetic Resonance Imaging (fMRI) changes in Blood Oxygenation Level-Dependent (BOLD) signal to test the hypothesis that NAc/internal capsule DBS results in global neural network activation in a large animal (porcine) model Methods Animals (n?=?10) were implanted in the NAc/internal capsule with DBS electrodes and received stimulation (1, 3, and 5 V, 130 Hz, and pulse widths of 100 and 500 sec). BOLD signal changes were evaluated using a gradient echo-echo planar imaging (GRE-EPI) sequence in 3.0 T MRI. We used a normalized functional activation map for group analysis and applied general linear modeling across subjects (FDR<0.001). The anatomical location of the implanted DBS lead was confirmed with a CT scan Results We observed stimulation-evoked activation in the ipsilateral prefrontal cortex, insula, cingulate and bilateral parahippocampal region along with decrease in BOLD signal in the ipsilateral dorsal region of the thalamus. Furthermore, as the stimulation voltage increased from 3 V to 5 V, the region of BOLD signal modulation increased in insula, thalamus, and parahippocampal cortex and decreased in the cingulate and prefrontal cortex. We also demonstrated that right and left NAc/internal capsule stimulation modulates identical areas ipsilateral to the side of the stimulation Conclusions Our results suggest that NAc/internal capsule DBS results in modulation of psychiatrically important brain areas notably the prefrontal cortex, cingulate, and insular cortex, which may underlie the therapeutic effect of NAc DBS in psychiatric disorders. Finally, our fMRI setup in the large animal may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS PMID:23441210

  13. Effects of Deep Brain Stimulation and Medication on Strength, Bradykinesia, and Electromyographic Patterns of the Ankle Joint in Parkinsons Disease

    PubMed Central

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

    2008-01-01

    We investigated the control of movement in 12 patients with Parkinsons 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. PMID:16124011

  14. 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 distal and axial signs in PD.

  15. A method for direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode.

    PubMed

    Shyu, Bai-Chuang; Lin, Chun-Yu; Sun, Jyh-Jang; Sylantyev, Sergiy; Chang, Chen

    2004-08-15

    Recent fMRI studies are of interest in exploring long-range interactions between different brain structures and the functional activation of specific brain regions by known neuroanatomical pathways. One of the experimental approaches requires the invasive implantation of an intracranial electrode to excite specific brain structures. In the present report, we describe a procedure for the production of a glass-coated carbon fiber electrode and the use of this electrode for direct activation of the brain in fMRI studies. The glass-coated carbon fiber microelectrode was implanted in the medial thalamus of anaesthetized rats and T2*-weighted gradient echo images in the sagittal plane obtained on a 4.7 T system (Biospec BMT 47/40) during electrical stimulation of the medial thalamus. The image quality obtained using this electrode was acceptable without reduction of the signal-to-noise ratio and image distortion. Cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral anterior cingulate cortex were significantly increased by about 4-5% during medial thalamus stimulation. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocingulate activation. PMID:15196834

  16. 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.

  17. 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-Mungua, 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

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

    PubMed

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

    2012-07-01

    Epilepsy affects approximately 1% 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

  19. Feasibility of combining gait robot and multichannel functional electrical stimulation with intramuscular electrodes.

    PubMed

    McCabe, Jessica P; Dohring, Mark E; Marsolais, E Byron; Rogers, Jean; Burdsall, Richard; Roenigk, Kristen; Pundik, Svetlana; Daly, Janis J

    2008-01-01

    After stroke rehabilitation, many survivors of stroke exhibit persistent gait deficits. In previous work, we demonstrated significant gains in gait kinematics for survivors of chronic stroke using multichannel functional electrical stimulation with intramuscular electrodes (FES-IM). For this study, we tested the feasibility of combining FES-IM and gait robot technologies for treating persistent gait deficits after stroke. Six subjects, >or= 6 months after stroke, received 30-minute intervention sessions of combined FES-IM and gait robotics 4 days a week for 12 weeks. Feasibility was assessed according to three factors: (1) performance of the interface of the two technologies during intervention sessions, (2) clinicians' success in using two technologies simultaneously, and (3) subject satisfaction. FES-IM system hardware and software design features combined with the gait robot technology proved feasible to use. Each technology alone provided unique advantages and disadvantages of gait practice characteristics. Because of the unique advantages and disadvantages of each technology, gait deficits need to be accurately identified and a judicious treatment plan properly targeted before FES-IM, a gait robot, or both combined are selected. PMID:19165689

  20. 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.

  1. 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 Central

    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. PMID:26509113

  2. Adaptive deep brain stimulation in Parkinson's disease

    PubMed Central

    Beudel, M.; Brown, P.

    2016-01-01

    Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application. PMID:26411502

  3. Adaptive deep brain stimulation in Parkinson's disease.

    PubMed

    Beudel, M; Brown, P

    2016-01-01

    Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application. PMID:26411502

  4. Transcutaneous focal electrical stimulation via concentric ring electrodes reduces synchrony induced by pentylenetetrazole in beta and gamma bands in rats.

    PubMed

    Besio, Walter G; Liu, Xiang; Wang, Liling; Medvedev, Andrei V; Koka, Kanthaiah

    2011-04-01

    Epilepsy is a neurological disorder that affects approximately one percent of the world population. Anti-epileptic drugs are ineffective in 25~30% of cases. Electrical stimulation to control seizures may be an additive therapy. We applied noninvasive transcutaneous focal electrical stimulation (TFES) via concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We found a significant increase in synchrony within the beta-gamma bands during seizures and that TFES significantly reduced the synchrony of the beta-gamma activity and increased synchrony in the delta band. PMID:21442777

  5. Recording of the Neural Activity Induced by the Electrical Subthalamic Stimulation Using Ca2+ Imaging

    NASA Astrophysics Data System (ADS)

    Tamura, Atsushi; Yagi, Tetsuya; Osanai, Makoto

    The basal ganglia (BG) have important roles in some kind of motor control and learning. Parkinson's disease is one of the motor impairment disease. Recently, to recover a motor severity in patients of Parkinsonism, the stimulus electrode is implanted to the subthalamic nucleus, which is a part of the basal ganglia, and the deep brain stimulation (DBS) is often conducted. However, the effects of the DBS on the subthalamic neurons have not been elucidated. Thus, to analyze the effects of the electrical stimulation on the subthalamic neurons, we conducted the calcium imaging at the mouse subthalamic nucleus. When the single stimulus was applied to the subthalamic nucleus, the intracellular calcium ([Ca2+]i) transients were observed. In the case of application of the single electrical stimulation, the [Ca2+]i arose near the stimulus position. When 100 Hz 10-100 times tetanic stimulations were applied, the responded area and the amplitudes of [Ca2+]i transients were increased. The [Ca2+]i transients were disappeared almost completely on the action potential blockade, but blockade of the excitatory and the inhibitory synaptic transmission had little effects on the responded area and the amplitudes of the [Ca2+]i transients. These results suggested that the electrical stimulation to the subthalamic neurons led to activate the subthalamic neurons directly but not via synaptic transmissions. Thus, DBS may change the activity of the subthalamic neurons, hence, may alter the input-output relationship of the subthalamic neurons

  6. Pillar-shaped stimulus electrode array for high-efficiency stimulation of fully implantable epiretinal prosthesis

    NASA Astrophysics Data System (ADS)

    Lee, Kang-Wook; Watanabe, Yoshinobu; Kigure, Chikashi; Fukushima, Takafumi; Koyanagi, Mitsumasa; Tanaka, Tetsu

    2012-10-01

    We developed a pillar-shaped microelectrode array (MEA) with varying heights for enhancing the spherical conformity of fully implantable epiretinal prosthesis comprising a 3D stacked retinal chip. The fabricated MEA is composed of 100 pillar electrodes with heights ranging from 60 to 80 m. The Pt-coated Cu pillar electrode with a surface diameter of 70 m and a height of 75 m and the Pt planar electrode with a surface diameter of 70 m have 24.6 and 125 k? impedances, respectively, at 1 kHz in vitro experiment. The pillar electrode shows lower impedance than the planar electrode because of a larger surface area. However, to avoid cross-talking between pillar electrodes, we developed a sidewall passivation process of the pillar electrode by using the surface tension of polyimide. The impedance of the isolated pillar electrode 116 k? at 1 kHz is similar to the impedance of the planar electrode, because they have similar electrode surface areas. The pillar-shaped MEA shows a better spherical conformity.

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

    PubMed

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

    2013-05-01

    Epilepsy affects approximately 1% 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

  8. 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.

  9. Electrode

    SciTech Connect

    Endoh, E.; Oda, Y.; Otouma, H.

    1981-03-10

    An electrode is prepared by etching an alloy substrate comprising a first metallic component selected from the group consisting of chromium, manganese, tantalum, niobium, vanadium, titanium, silicon, zirconium, germanium, scandium, yttrium and lanthanum and a second metallic component selected from the group consisting of iron, nickel, tungsten, copper, silver, cobalt and molybdenum to remove at least part of the first metallic component.

  10. 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 m 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 m 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 m 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 m with 95% confidence and the intracortical stimulation method estimates it within 69.3 m. We propose that these methods can be used to estimate the in situ location of laminar electrodes implanted in the rat motor cortex.

  11. High frequency activation data used to validate localization of cortical electrodes during surgery for deep brain stimulation.

    PubMed

    Kondylis, Efstathios D; Randazzo, Michael J; Alhourani, Ahmad; Wozny, Thomas A; Lipski, Witold J; Crammond, Donald J; Richardson, R Mark

    2016-03-01

    Movement related synchronization of high frequency activity (HFA, 76-100 Hz) is a somatotopic process with spectral power changes occurring during movement in the sensorimotor cortex (Miller et al., 2007) [1]. These features allowed movement-related changes in HFA to be used to functionally validate the estimations of subdural electrode locations, which may be placed temporarily for research in deep brain stimulation surgery, using the novel tool described in Randazzo et al. (2015) [2]. We recorded electrocorticography (ECoG) signals and localized electrodes in the region of the sensorimotor cortex during an externally cued hand grip task in 8 subjects. Movement related HFA was determined for each trial by comparing HFA spectral power during movement epochs to pre-movement baseline epochs. Significant movement related HFA was found to be focal in time and space, occurring only during movement and only in a subset of electrodes localized to the pre- and post-central gyri near the hand knob. To further demonstrate the use of movement related HFA to aid electrode localization, we provide a sample of the electrode localization tool, with data loaded to allow readers to map movement related HFA onto the cortical surface of a sample patient. PMID:26862560

  12. High frequency activation data used to validate localization of cortical electrodes during surgery for deep brain stimulation

    PubMed Central

    Kondylis, Efstathios D.; Randazzo, Michael J.; Alhourani, Ahmad; Wozny, Thomas A.; Lipski, Witold J.; Crammond, Donald J.; Richardson, R. Mark

    2015-01-01

    Movement related synchronization of high frequency activity (HFA, 76100Hz) is a somatotopic process with spectral power changes occurring during movement in the sensorimotor cortex (Miller et al., 2007) [1]. These features allowed movement-related changes in HFA to be used to functionally validate the estimations of subdural electrode locations, which may be placed temporarily for research in deep brain stimulation surgery, using the novel tool described in Randazzo et al. (2015)[2]. We recorded electrocorticography (ECoG) signals and localized electrodes in the region of the sensorimotor cortex during an externally cued hand grip task in 8 subjects. Movement related HFA was determined for each trial by comparing HFA spectral power during movement epochs to pre-movement baseline epochs. Significant movement related HFA was found to be focal in time and space, occurring only during movement and only in a subset of electrodes localized to the pre- and post-central gyri near the hand knob. To further demonstrate the use of movement related HFA to aid electrode localization, we provide a sample of the electrode localization tool, with data loaded to allow readers to map movement related HFA onto the cortical surface of a sample patient. PMID:26862560

  13. 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 target finalization during DBS surgery for PD.

  14. Deep brain stimulation of the subthalamic nucleus preferentially alters the translational profile of striatopallidal neurons in an animal model of Parkinson's disease.

    PubMed

    Visanji, Naomi P; Kamali Sarvestani, Iman; Creed, Meaghan C; Shams Shoaei, Zahra; Nobrega, José N; Hamani, Clement; Hazrati, Lili-Naz

    2015-01-01

    Deep brain stimulation targeting the subthalamic nucleus (STN-DBS) is an effective surgical treatment for the motor symptoms of Parkinson's disease (PD), the precise neuronal mechanisms of which both at molecular and network levels remain a topic of debate. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP) with bacterial artificial chromosome expression (Bac), to selectively identify changes in translational gene expression in either Drd1a-expressing striatonigral or Drd2-expressing striatopallidal medium spiny neurons (MSNs) of the striatum following STN-DBS. 6-hydroxydopamine lesioned mice received either 5 days stimulation via a DBS electrode implanted in the ipsilateral STN or 5 days sham treatment (no stimulation). Striatal polyribosomal RNA was selectively purified from either Drd2 or Drd1a MSNs using the TRAP method and gene expression profiling performed. We identified eight significantly altered genes in Drd2 MSNs (Vps33b, Ppp1r3c, Mapk4, Sorcs2, Neto1, Abca1, Penk1, and Gapdh) and two overlapping genes in Drd1a MSNs (Penk1 and Ppp1r3c) implicated in the molecular mechanisms of STN-DBS. A detailed functional analysis, using a further 728 probes implicated in STN-DBS, suggested an increased ability to receive excitation (mediated by increased dendritic spines, increased calcium influx and enhanced excitatory post synaptic potentials) accompanied by processes that would hamper the initiation of action potentials, transport of neurotransmitters from soma to axon terminals and vesicular release in Drd2-expressing MSNs. Finally, changes in expression of several genes involved in apoptosis as well as cholesterol and fatty acid metabolism were also identified. This increased understanding of the molecular mechanisms induced by STN-DBS may reveal novel targets for future non-surgical therapies for PD. PMID:26106299

  15. Deep brain stimulation of the subthalamic nucleus preferentially alters the translational profile of striatopallidal neurons in an animal model of Parkinson's disease

    PubMed Central

    Visanji, Naomi P.; Kamali Sarvestani, Iman; Creed, Meaghan C.; Shams Shoaei, Zahra; Nobrega, Jos N.; Hamani, Clement; Hazrati, Lili-Naz

    2015-01-01

    Deep brain stimulation targeting the subthalamic nucleus (STN-DBS) is an effective surgical treatment for the motor symptoms of Parkinson's disease (PD), the precise neuronal mechanisms of which both at molecular and network levels remain a topic of debate. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP) with bacterial artificial chromosome expression (Bac), to selectively identify changes in translational gene expression in either Drd1a-expressing striatonigral or Drd2-expressing striatopallidal medium spiny neurons (MSNs) of the striatum following STN-DBS. 6-hydroxydopamine lesioned mice received either 5 days stimulation via a DBS electrode implanted in the ipsilateral STN or 5 days sham treatment (no stimulation). Striatal polyribosomal RNA was selectively purified from either Drd2 or Drd1a MSNs using the TRAP method and gene expression profiling performed. We identified eight significantly altered genes in Drd2 MSNs (Vps33b, Ppp1r3c, Mapk4, Sorcs2, Neto1, Abca1, Penk1, and Gapdh) and two overlapping genes in Drd1a MSNs (Penk1 and Ppp1r3c) implicated in the molecular mechanisms of STN-DBS. A detailed functional analysis, using a further 728 probes implicated in STN-DBS, suggested an increased ability to receive excitation (mediated by increased dendritic spines, increased calcium influx and enhanced excitatory post synaptic potentials) accompanied by processes that would hamper the initiation of action potentials, transport of neurotransmitters from soma to axon terminals and vesicular release in Drd2-expressing MSNs. Finally, changes in expression of several genes involved in apoptosis as well as cholesterol and fatty acid metabolism were also identified. This increased understanding of the molecular mechanisms induced by STN-DBS may reveal novel targets for future non-surgical therapies for PD. PMID:26106299

  16. 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.

  17. Deep brain stimulation for obesity: past, present, and future targets.

    PubMed

    Dupr, 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. PMID:26030707

  18. Postmortem volumetric analysis of the nucleus accumbens in male heroin addicts: implications for deep brain stimulation.

    PubMed

    Müller, Ulf J; Truebner, Kurt; Schiltz, Kolja; Kuhn, Jens; Mawrin, Christian; Dobrowolny, Henrik; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

    2015-12-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is increasingly investigated in neuropsychiatric disorders. DBS requires computer-assisted 3D planning to implant the stimulation electrode precisely. Recently, there has been a debate about the true dimensions of NAc in healthy as well as in mentally ill individuals. Knowing its true dimensions in different neuropsychiatric disorders may improve even more precise targeting of NAc for therapeutic DBS. Volumes of NAc of heroin addicts (n = 14) and healthy controls (n = 12) were calculated by using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1478.85 ± 62.34 vs. mean 1352.38 ± 103.24 cm(3)), as the heroin group was more than 10 years younger (p = 0.001). However, the mean volume of the NAc in heroin addicts was smaller than in controls (0.528 ± 0.166 vs. 0.623 ± 0.196 cm(3); p = 0.019). This group effect did not significantly differ between the hemispheres. When assessed separately, left-hemispheric NAc volume was 15 % lower (p = 0.020), while right-hemispheric NAc volume was 16 % lower (p = 0.047) in the heroin-addicted group compared to controls. Based on these diagnosis-related differences, we believe it is important to further analyze NAc volumes in different psychiatric disorders to further improve precise targeting and electrode placement. PMID:26189034

  19. Technical and economic models of a DBS system for Canada

    NASA Astrophysics Data System (ADS)

    Roscoe, O. S.

    A comprehensive, multidisciplinary study program to develop information regarding the possible implementation of a direct broadcasting satellite system for Canada was completed in 1983. The program included market studies and technical and economic modeling of alternative DBS systems. Both 50 dBW and 54 dBW edge-of-coverage EIRP systems were modeled, with both 4 and 6 beam coverage. It is estimated that an eight to ten channel system for Canada would cost between $400 million and $650 million (1982 Canadian dollars). The main requirement for DBS television service is in rural Canada. Market forecasts are that up to 2-1/2 million households would purchase DBS home receivers. Allowing for a real rate of return of 6 percent, the monthly cost per household for delivery of all channels would range from $5 to $7.

  20. 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. PMID:26159102

  1. Subthalamic nucleus deep brain stimulation in elderly patients analysis of outcome and complications

    PubMed Central

    Vesper, Jan; Haak, Susanne; Ostertag, Christoph; Nikkhah, Guido

    2007-01-01

    Background There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. Methods Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age ? 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. Results Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. Conclusion DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate. PMID:17367531

  2. 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.

  3. 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; Jaki?, 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??m 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 560700?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

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

    PubMed

    Forneris, Jacopo; Traina, Paolo; Monticone, Daniele Gatto; Amato, Giampiero; Boarino, Luca; Brida, Giorgio; Degiovanni, Ivo P; Enrico, Emanuele; Moreva, Ekaterina; Grilj, Veljko; Skukan, Natko; Jaki?, 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 ?m 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

  5. 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.

  6. Fabrication and functional demonstration of a smart electrode with a built-in CMOS microchip for neural stimulation of a retinal prosthesis.

    PubMed

    Noda, Toshihiko; Fujisawa, Takumi; Kawasaki, Ryohei; Tashiro, Hiroyuki; Takehara, Hiroaki; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

    2015-08-01

    In this study, we propose an advanced architecture of a smart electrode for neural stimulation of a retinal prosthesis. A feature of the proposed architecture is embedding CMOS microchips into the core of the stimulus electrodes. Microchip integration without dead space on the array is possible. Additionally, higher durability can be expected because the microchips are protected by the stimulus electrodes like a metal casing. Dedicated circular-shaped CMOS microchips were designed and fabricated. The microchip measured 400 ?m in diameter. Stimulus electrodes that had a microcavity for embedding the microchip were also fabricated. In the assembly process, the CMOS microchip was mounted on a flexible substrate, and then the stimulus electrode was mounted to cover the microchip. The microchip was completely built into the inside of the electrode. By performing an ex-vivo experiment using the extracted eyeball of a pig, stimulus function of the electrode was demonstrated successfully. PMID:26737011

  7. 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

  8. Weight Changes in STN versus GPi DBS: Results from the COMPARE Parkinson’s Disease DBS Cohort

    PubMed Central

    Locke, Maren; Wu, Samuel; Foote, Kelly; Sassi, Marco; Jacobson, Charles; Rodriguez, Ramon; Fernandez, Hubert; Okun, Michael

    2011-01-01

    Background Parkinson’s patients, on average, gain weight following DBS. Objective To determine potential differences in weight gain when comparing the STN versus the GPi target. Methods A retrospective analysis was performed on the prospective randomized cohort of NIH COMPARE DBS patients who received unilateral STN or GPi DBS. Baseline weights were recorded prior to DBS surgery and at 6, 12, and 18 months post-operatively. Relationships between weight change and changes in BDI score, UPDRS motor score (part III) (also the dyskinesia duration and disability subscores from UPDRS IV), and HY stage were determined via Spearman’s rank order correlation coefficients. Regression analyses were performed to investigate the effects of potential factors on weight change over time. Results Patients in the COMPARE DBS cohort gained a significant amount of weight-a mean of 4.86 lbs (SD 8.73) (p-value = 0.0006), but there was no significant difference between STN and GPi targets (weight gain of 4.29± 6.79 and 5.38±10.32 pounds, respectively; p-value = 0.684). Weight gain did not correlate with BDI score change, UPDRS motor score, dyskinesia duration, dyskinesia disability change, or the HY stage (p-values were0.617, 0.210, and 0.305 respectively). No specific variable was associated with weight gain, and there were no differences in binge eating post-surgery in either target. Conclusion There were significant changes in weight over time following DBS therapy. However, neither BDI score change nor UPDRS score change or dyskinesia was correlated with weight gain. No significant factor was associated with the weight change. PMID:21273927

  9. Hindlimb movement in the cat induced by amplitude-modulated stimulation using extra-spinal electrodes

    NASA Astrophysics Data System (ADS)

    Tai, Changfeng; Wang, Jicheng; Shen, Bing; Wang, Xianchun; Roppolo, James R.; de Groat, William C.

    2008-06-01

    Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of the L5-S1 spinal cord or the L5-S1 dorsal/ventral roots was investigated before and after acute spinal cord transection at the T13-L1 level. Stimulation of the spinal cord or dorsal/ventral root at the same spinal segment induced similar movements including coordinated multi-joint flexion or extension. The induced movements changed from flexion to extension when the stimulation was moved from rostral (L5) to caudal (S1) spinal segments. Stimulation of a dorsal or ventral root on one side induced only ipsilateral hindlimb movement. However, stimulation on the dorsal surface of the spinal cord along the midline or across the spinal cord induced bilateral movements. The extension induced by stimulation of L7 dorsal root produced the largest ground reaction force that was strong enough to support body weight. Dorsal root stimulation induced a larger ground reaction force than ventral root stimulation and produced a more graded recruitment curve. Stepping at different speeds could be generated by combined stimulation of the rostral (L5) and the caudal (L6/L7) spinal segments with an appropriate timing between the different stimulation channels. Acute transection of the spinal cord did not change the responses indicating that the induced movements did not require the involvement of the supraspinal locomotor centers. The methods and the stimulation strategy developed in this study might be utilized to restore locomotor function after spinal cord injury.

  10. Pedunculopontine stimulation from primate to patient.

    PubMed

    Pereira, Erlick A C; Nandi, Dipankar; Jenkinson, Ned; Stein, John F; Green, Alexander L; Aziz, Tipu Z

    2011-10-01

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinson's disease and related disorders. Here we summarise our non-human primate investigations of relevance to our surgical targeting of the PPN and relate the primate research to initial clinical experience of PPN DBS. PMID:21448675

  11. Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation.

    PubMed Central

    Wikswo, J P; Lin, S F; Abbas, R A

    1995-01-01

    Traditional cable analyses cannot explain complex patterns of excitation in cardiac tissue with unipolar, extracellular anodal, or cathodal stimuli. Epifluorescence imaging of the transmembrane potential during and after stimulation of both refractory and excitable tissue shows distinctive regions of simultaneous depolarization and hyperpolarization during stimulation that act as virtual cathodes and anodes. The results confirm bidomain model predictions that the onset (make) of a stimulus induces propagation from the virtual cathode, whereas stimulus termination (break) induces it from the virtual anode. In make stimulation, the virtual anode can delay activation of the underlying tissue, whereas in break stimulation this occurs under the virtual cathode. Thus make and break stimulations in cardiac tissue have a common mechanism that is the result of differences in the electrical anisotropy of the intracellular and extracellular spaces and provides clear proof of the validity of the bidomain model. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:8599628

  12. Emotion recognition in Parkinson's disease after subthalamic deep brain stimulation: differential effects of microlesion and STN stimulation.

    PubMed

    Aiello, Marilena; Eleopra, Roberto; Lettieri, Christian; Mondani, Massimo; D'Auria, Stanislao; Belgrado, Enrico; Piani, Antonella; De Simone, Luca; Rinaldo, Sara; Rumiati, Raffaella I

    2014-02-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) has acquired a relevant role in the treatment of Parkinson's disease (PD). Despite being a safe procedure, it may expose patients to an increased risk to experience cognitive and emotional difficulties. Impairments in emotion recognition, mediated both by facial and prosodic expressions, have been reported in PD patients treated with such procedure. However, it is still unclear whether the STN per se is responsible for such changes or whether others factors like the microlesion produced by the electrode implantation may also play a role. In this study we evaluated facial emotions discrimination and emotions recognition using both facial and prosodic expressions in 12 patients with PD and 13 matched controls. Patients' were tested in four conditions: before surgery, both in on and off medication, and after surgery, respectively few days after STN implantation before turning stimulator on and few months after with stimulation on. We observed that PD patients were impaired in discriminating and recognizing facial emotions, especially disgust, even before DBS implant. Microlesion caused by surgical procedure was found to influence patients' performance on the discrimination task and recognition of sad facial expression while, after a few months of STN stimulation, impaired disgust recognition was again prominent. No impairment in emotional prosody recognition was observed both before and after surgery. Our study confirms that PD patients may experience a deficit in disgust recognition and provides insight into the differential effect of microlesion and stimulation of STN on several tasks assessing emotion recognition. PMID:24342106

  13. 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…

  14. Acute and Chronic Mood and Apathy Outcomes from a Randomized Study of Unilateral STN and GPi DBS

    PubMed Central

    Okun, Michael S.; Wu, Samuel S.; Fayad, Sarah; Ward, Herbert; Bowers, Dawn; Rosado, Christian; Bowen, Lauren; Jacobson, Charles; Butson, Christopher; Foote, Kelly D.

    2014-01-01

    Objective To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD). Background There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction. Methods A standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed. Results Thirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases. Conclusions There were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach. PMID:25469706

  15. Symptomatic treatment of memory decline in Alzheimer's disease by deep brain stimulation: a feasibility study.

    PubMed

    Fontaine, Denys; Deudon, Audrey; Lemaire, Jean Jacques; Razzouk, Micheline; Viau, Philippe; Darcourt, Jacques; Robert, Philippe

    2013-01-01

    Recent studies have suggested that memory circuits can be modulated by deep brain stimulation (DBS). This propriety might be used to slow down cognitive decline in patients suffering from Alzheimer's disease (AD). We conducted a prospective study to evaluate the feasibility and safety of DBS in AD patients with mild cognitive decline. Inclusion criteria were: patients (<70 years old) with AD diagnosed for less than 2 years, predominant impairment of episodic memory, and Mini-Mental Status Exam (MMSE) score between 20 and 24. The fornix was stimulated bilaterally by electrodes implanted stereotactically in the hypothalamus. Clinical, biological, neuropsychological, and imaging evaluations were conducted 3 months before surgery and 3, 6, and 12 months thereafter. During the one year-period of inclusion, 110 patients with recently diagnosed AD and predominant impairment of episodic memory were screened. Only 9 patients (8.2%) fulfilled all the inclusion criteria. Finally, just one patient accepted to be operated (acceptance rate 11.1%) and completed the study. No complications occurred and the stimulation was perfectly tolerated. After one year of stimulation, the memory scores (MMSE, ADAS-Cog, Free and Cued Selective Reminding Test) were stabilized compared to baseline, and mesial temporal lobes metabolism increased. This pilot study provides new data about the safety of fornix DBS in the hypothalamus. However, it suggests that only a small proportion of AD patients might be interested in this approach and that the acceptance of DBS by AD patients was low, raising questions about the relevance of this approach to meet the expectations of these patients. PMID:23168448

  16. 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. PMID:23232663

  17. Deep Brain Stimulation of the Subthalamic and Pedunculopontine Nucleus in a Patient with Parkinson's Disease

    PubMed Central

    Liu, Huan-Guang; Zhang, Kai; Yang, An-Chao

    2015-01-01

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel therapy developed to treat Parkinson's disease. We report a patient who underwent bilateral DBS of the PPN and subthalamic nucleus (STN). He suffered from freezing of gait (FOG), bradykinesia, rigidity and mild tremors. The patient underwent bilateral DBS of the PPN and STN. We compared the benefits of PPN-DBS and STN-DBS using motor and gait subscores. The PPN-DBS provided modest improvements in the gait disorder and freezing episodes, while the STN-DBS failed to improve the dominant problems. This special case suggests that PPN-DBS may have a unique role in ameliorating the locomotor symptoms and has the potential to provide improvement in FOG. PMID:25932301

  18. Deep brain stimulation of the subthalamic and pedunculopontine nucleus in a patient with Parkinson's disease.

    PubMed

    Liu, Huan-Guang; Zhang, Kai; Yang, An-Chao; Zhang, Jian-Guo

    2015-04-01

    Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel therapy developed to treat Parkinson's disease. We report a patient who underwent bilateral DBS of the PPN and subthalamic nucleus (STN). He suffered from freezing of gait (FOG), bradykinesia, rigidity and mild tremors. The patient underwent bilateral DBS of the PPN and STN. We compared the benefits of PPN-DBS and STN-DBS using motor and gait subscores. The PPN-DBS provided modest improvements in the gait disorder and freezing episodes, while the STN-DBS failed to improve the dominant problems. This special case suggests that PPN-DBS may have a unique role in ameliorating the locomotor symptoms and has the potential to provide improvement in FOG. PMID:25932301

  19. 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

  20. 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.

  1. 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.

  2. Intact Lexicon Running Slowly Prolonged Response Latencies in Patients with Subthalamic DBS and Verbal Fluency Deficits

    PubMed Central

    Ehlen, Felicitas; Krugel, Lea K.; Vonberg, Isabelle; Schoenecker, Thomas; Khn, Andrea A.; Klostermann, Fabian

    2013-01-01

    Background Verbal Fluency is reduced in patients with Parkinsons disease, particularly if treated with deep brain stimulation. This deficit could arise from general factors, such as reduced working speed or from dysfunctions in specific lexical domains. Objective To test whether DBS-associated Verbal Fluency deficits are accompanied by changed dynamics of word processing. Methods 21 Parkinsons disease patients with and 26 without deep brain stimulation of the subthalamic nucleus as well as 19 healthy controls participated in the study. They engaged in Verbal Fluency and (primed) Lexical Decision Tasks, testing phonemic and semantic word production and processing time. Most patients performed the experiments twice, ON and OFF stimulation or, respectively, dopaminergic drugs. Results Patients generally produced abnormally few words in the Verbal Fluency Task. This deficit was more severe in patients with deep brain stimulation who additionally showed prolonged response latencies in the Lexical Decision Task. Slowing was independent of semantic and phonemic word priming. No significant changes of performance accuracy were obtained. The results were independent from the treatment ON or OFF conditions. Conclusion Low word production in patients with deep brain stimulation was accompanied by prolonged latencies for lexical decisions. No indication was found that the latter slowing was due to specific lexical dysfunctions, so that it probably reflects a general reduction of cognitive working speed, also evident on the level of Verbal Fluency. The described abnormalities seem to reflect subtle sequelae of the surgical procedure for deep brain stimulation rather than of the proper neurostimulation. PMID:24236114

  3. Flexible Nerve Stimulation Electrode with Iridium Oxide Sputtered on Liquid Crystal Polymer

    PubMed Central

    Wang, Kevin; Liu, Chung-Chiun; Durand, Dominique M.

    2009-01-01

    Current electrode designs require flexible substrates that absorb little moisture and provide large charge injection capability. Sputtered iridium oxide films have superior charge injection capabilities versus noble metals and can adhere to various substrates. Liquid crystal polymers (LCP) have very little water absorption compared to other flexible substrates. Therefore, the combination of sputtered iridium oxide film on liquid crystal polymer substrate was studied using 50Hz, 100?s duration, 10mA biphasic current waveforms for 700 hours at 67C in bicarbonate buffer saline. Scanning electron micrograph (SEM) analysis showed no delamination and approximately 1% of electrode material was lost to the bicarbonate buffer. The charge injection limit and the cathodic charge storage capacity within the water window were 4.6 +/? 1.0mC/cm2 and 31.5 +/? 6.6mC/cm2 respectively. Additional electrochemical analysis revealed significant charge imbalance attributed to oxygen reduction within the water window. These results, along with the flexible, chemically inert, biocompatible substrate, indicate that sputtered iridium oxide films on liquid crystal polymer could become the method of choice for flexible substrate nerve electrodes. PMID:19224713

  4. Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

    PubMed Central

    Chang, Su-Youne; Kimble, Christopher J.; Kim, Inyong; Paek, Seungleal B.; Kressin, Kenneth R.; Boesche, Joshua B.; Whitlock, Sidney V.; Eaker, Diane R.; Kasasbeh, Aimen; Horne, April E.; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.

    2014-01-01

    Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application. PMID:24116724

  5. Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats

    PubMed Central

    2013-01-01

    Background Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. Methods We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1100Hz and 110V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. Results In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1Hz stimulation in the absence of any anesthesia. Conclusions Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles. PMID:23336733

  6. Stimulants

    MedlinePLUS

    Stimulants are drugs that increase your heart rate, breathing rate, and brain function. Some stimulants affect only a specific organ, such as the heart, lungs, brain, or nervous system. Epinephrine ...

  7. Influence of propofol and fentanyl on deep brain stimulation of the subthalamic nucleus.

    PubMed

    Kim, Wonki; Song, In Ho; Lim, Yong Hoon; Kim, Mi-Ryoung; Kim, Young Eun; Hwang, Jae Ha; Kim, In Keyoung; Song, Sang Woo; Kim, Jin Wook; Lee, Woong-Woo; Kim, Han-Joon; Kim, Cheolyoung; Kim, Hee Chan; Kim, In Young; Park, Hee Pyoung; Kim, Dong Gyu; Jeon, Beom Seok; Paek, Sun Ha

    2014-09-01

    We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7 16.8 spikes/sec, n=78) and the right side MERs (35.5 17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients. PMID:25246748

  8. 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

  9. Selectivity of Direct and Network-mediated Stimulation of the Retinal Ganglion Cells with Epi-, Sub- and Intra-Retinal Electrodes

    PubMed Central

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

    2014-01-01

    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 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, ?<5ms) originating in RGCs, medium latency (ML, 340ms) 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 0.5ms. 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 10ms. Latency of all three types of responses decreased with increasing strength of the stimulus. Significance These results define optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs. PMID:24608166

  10. Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 μm CMOS chip.

    PubMed

    Huys, Roeland; Braeken, Dries; Jans, Danny; Stassen, Andim; Collaert, Nadine; Wouters, Jan; Loo, Josine; Severi, Simone; Vleugels, Frank; Callewaert, Geert; Verstreken, Kris; Bartic, Carmen; Eberle, Wolfgang

    2012-04-01

    To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 μm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks. PMID:22337001

  11. 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

  12. Could deep brain stimulation help with driving for patients with Parkinson's?

    PubMed

    Buhmann, Carsten; Gerloff, Christian

    2014-09-01

    For mobility impaired people with Parkinson's disease (PD), driving a car is important to maintain independency. But driving ability is getting worse with disease progression. Meanwhile surgical treatment with deep brain stimulation (DBS) of the subthalamic nucleus is done routinely in advanced PD, but it is unknown how DBS might affect driving. In a driving simulator setting, we found PD patients undergone DBS surgery to drive safer than even less clinically affected PD patients treated with medication alone. Furthermore, patients with DBS surgery drove better under stimulation than under medication. In conclusion, DBS of the subthalamic nucleus appears to be beneficial for driving in PD patients, potentially due to non-motor effects on controlling the vehicle in the simulator setting. Nevertheless, results of this first pilot study on driving in PD patients with DBS should not encourage patients or physicians to consider DBS only to improve or regain driving competence. PMID:24930934

  13. REACHING TO PROPRIOCEPTIVELY DEFINED TARGETS IN PARKINSONS DISEASE: EFFECTS OF DEEP BRAIN STIMULATION THERAPY

    PubMed Central

    LEE, D.; HENRIQUES, D. Y.; SNIDER, J.; SONG, D.; POIZNER, H.

    2013-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) provides a unique window into human brain function since it can reversibly alter the functioning of specific brain circuits. Basal gangliacortical circuits are thought to be excessively noisy in patients with Parkinsons disease (PD), based in part on the lack of specificity of proprioceptive signals in basal gangliathalamiccortical circuits in monkey models of the disease. PD patients are known to have deficits in proprioception, but the effects are often subtle, with paradigms typically restricted to one or two joint movements in a plane. Moreover, the effects of STN DBS on proprioception are virtually unexplored. We tested the following hypotheses: first, that PD patients will show substantial deficits in unconstrained, multi-joint proprioception, and, second, that STN DBS will improve multi-joint proprioception. Twelve PD patients with bilaterally implanted electrodes in the subthalamic nucleus and 12 age-matched healthy subjects were asked to position the left hand at a location that was proprioceptively defined in 3D space with the right hand. In a second condition, subjects were provided visual feedback during the task so that they were not forced to rely on proprioception. Overall, with STN DBS switched off, PD patients showed significantly larger proprioceptive localization errors, and greater variability in endpoint localizations than the control subjects. Visual feedback partially normalized PD performance, and demonstrated that the errors in proprioceptive localization were not simply due to a difficulty in executing the movements or in remembering target locations. Switching STN DBS on significantly reduced localization errors from those of control subjects when patients moved without visual feedback relative to when they moved with visual feedback (when proprioception was not required). However, this reduction in localization errors without vision came at the cost of increased localization variability. PMID:23590906

  14. 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. PMID:25161150

  15. 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

  16. 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 to be recruited to future fMRI experiments performed under the specific conditions defined by our protocol, with no likelihood of confound by inappropriate stimulus delivery. PMID:26061738

  17. 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

  18. The present indication and future of deep brain stimulation.

    PubMed

    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

  19. 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. PMID:25296166

  20. Nonmotor Symptoms and Subthalamic Deep Brain Stimulation in Parkinson's Disease.

    PubMed

    Kim, Han-Joon; Jeon, Beom S; Paek, Sun Ha

    2015-05-01

    Subthalamic deep brain stimulation (STN DBS) is an established treatment for the motor symptoms in patients with advanced Parkinson's disease (PD). In addition to improvements in motor symptoms, many studies have reported changes in various nonmotor symptoms (NMSs) after STN DBS in patients with PD. Psychiatric symptoms, including depression, apathy, anxiety, and impulsivity, can worsen or improve depending on the electrical stimulation parameters, the locations of the stimulating contacts within the STN, and changes in medications after surgery. Global cognitive function is not affected by STN DBS, and there is no increase in the incidence of dementia after STN DBS compared to that after medical treatment, although clinically insignificant declines in verbal fluency have been consistently reported. Pain, especially PD-related pain, improves with STN DBS. Evidence regarding the effects of STN DBS on autonomic symptoms and sleep-related problems is limited and remains conflicting. Many symptoms of nonmotor fluctuations, which are occasionally more troublesome than motor fluctuations, improve with STN DBS. Although it is clear that NMSs are not target symptoms for STN DBS, NMSs have a strong influence on the quality of life of patients with PD, and clinicians should thus be aware of these NMSs when deciding whether to perform surgery and should pay attention to changes in these symptoms after STN DBS to ensure the optimal care for patients. PMID:26090080

  1. 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 connected to the already existing WebBioBank Web-based platform allowing health care professionals to manage patient electronic health records and neurophysiological signals. New modules in the WebBioBank platform will be implemented to allow integration and data exchange with mobile health apps. Results The results of this project will provide a novel approach to long-term evaluation of patients with chronic, severe conditions in the homecare environment, based on caregiver empowerment and tailored applications developed according to consensus care pathways established by clinicians. Conclusions The creation of a direct communication channel between health care professionals and caregivers can benefit large communities of patients and would represent a scalable experience in integrating data and information coming from a clinical setting to those in home monitoring. PMID:25803512

  2. Unilateral Subthalamic Nucleus Stimulation Has a Measurable Ipsilateral Effect on Rigidity And Bradykinesia in Parkinson Disease

    PubMed Central

    Tabbal, Samer D.; Ushe, Mwiza; Mink, Jonathan W.; Revilla, Fredy J.; Wernle, Angie R.; Hong, Minna; Karimi, Morvarid; Perlmutter, Joel S.

    2008-01-01

    Background Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in Parkinson disease (PD). However, little is known about the quantitative effects on motor behavior of unilateral STN DBS. Methods In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity (n= 42), bradykinesia (n= 38), and gait speed (n= 45). Subjects were tested in four DBS conditions: both on, left on, right on and both off. A force transducer was used to measure rigidity across the elbow, and gyroscopes were used to measure angular velocity of hand rotations for bradykinesia. About half of the subjects were rated using the Unified Parkinson Disease Rating Scale (part III) motor scores for arm rigidity and repetitive hand rotation simultaneously during the kinematic measurements. Subjects were timed walking 25 feet. Results All subjects had significant improvement with bilateral STN DBS. Contralateral, ipsilateral and bilateral stimulation significantly reduced rigidity and bradykinesia. Bilateral stimulation improved rigidity more than unilateral stimulation of either side, but there was no significant difference between ipsilateral and contralateral stimulation. Although bilateral stimulation also increased hand rotation velocity more than unilateral stimulation of either side, contralateral stimulation increased hand rotation significantly more than ipsilateral stimulation. All stimulation conditions improved walking time but bilateral stimulation provided the greatest improvement. Conclusions Unilateral STN DBS decreased rigidity and bradykinesia contralaterally as well ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS. These findings suggest that unilateral STN DBS alters pathways that affect rigidity and bradykinesia bilaterally but do not support the clinical use of unilateral STN DBS since bilateral DBS clearly provides greater benefit. PMID:18329019

  3. [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. PMID:27017772

  4. Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode.

    PubMed

    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 microm electrode placed on the inner retinal surface within the receptive field of a RGC, produced both short-latency (< or =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 microA for a cathodal stimulus and 21 microA for an anodal stimulus. In ON RGCs, the average threshold current was 13 microA for a cathodal stimulus and 15 microA for an anodal stimulus. PMID:15876650

  5. 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 m 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 A for a cathodal stimulus and 21 A for an anodal stimulus. In ON RGCs, the average threshold current was 13 A for a cathodal stimulus and 15 A for an anodal stimulus.

  6. 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. PMID:24112895

  7. Deep Brain Stimulation: Expanding Applications.

    PubMed

    Tekriwal, Anand; Baltuch, Gordon

    2015-12-15

    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

  8. 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

  9. Deep brain stimulation for psychiatric diseases: what are the risks?

    PubMed

    Saleh, Christian; Fontaine, Denys

    2015-05-01

    Despite the application of deep brain stimulation (DBS) as an efficient treatment modality for psychiatric disorders, such as obsessive-compulsive disorder (OCD), Gilles de la Tourette Syndrome (GTS), and treatment refractory major depression (TRD), few patients are operated or included in clinical trials, often for fear of the potential risks of an approach deemed too dangerous. To assess the surgical risks, we conducted an analysis of publications on DBS for psychiatric disorders. A PubMed search was conducted on reports on DBS for OCD, GTS, and TRD. Forty-nine articles were included. Only reports on complications related to DBS were selected and analyzed. Two hundred seventy-two patients with a mean follow-up of 22 months were included in our analysis. Surgical mortality was nil. The overall mortality was 1.1 %: two suicides were unrelated to DBS and one death was reported to be unlikely due to DBS. The majority of complications were transient and related to stimulation. Long-term morbidity occurred in 16.5 % of cases. Three patients had permanent neurological complications due to intracerebral hemorrhage (2.2 %). Complications reported in DBS for psychiatric diseases appear to be similar to those reported for DBS in movement disorders. But class I evidence is lacking. Our analysis was based mainly on small non-randomized studies. A significant number of patients (approximately 150 patients) who were treated with DBS for psychiatric diseases had to be excluded from our analysis as no data on complications was available. The exact prevalence of complications of DBS in psychiatric diseases could not be established. DBS for psychiatric diseases is promising, but remains an experimental technique in need of further evaluation. A close surveillance of patients undergoing DBS for psychiatric diseases is mandatory. PMID:25795265

  10. 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.

  11. 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.

  12. Upper-limb stroke rehabilitation using electrode-array based functional electrical stimulation with sensing and control innovations.

    PubMed

    Kutlu, M; Freeman, C T; Hallewell, E; Hughes, A-M; Laila, D S

    2016-04-01

    Functional electrical stimulation (FES) has shown effectiveness in restoring upper-limb movement post-stroke when applied to assist participants' voluntary intention during repeated, motivating tasks. Recent clinical trials have used advanced controllers that precisely adjust FES to assist functional reach and grasp tasks with FES applied to three muscle groups, showing significant reduction in impairment. The system reported in this paper advances the state-of-the-art by: (1) integrating an FES electrode array on the forearm to assist complex hand and wrist gestures; (2) utilising non-contact depth cameras to accurately record the arm, hand and wrist position in 3D; and (3) employing an interactive touch table to present motivating virtual reality (VR) tasks. The system also uses iterative learning control (ILC), a model-based control strategy which adjusts the applied FES based on the tracking error recorded on previous task attempts. Feasibility of the system has been evaluated in experimental trials with 2 unimpaired participants and clinical trials with 4 hemiparetic, chronic stroke participants. The stroke participants attended 17, 1 hour training sessions in which they performed functional tasks, such as button pressing using the touch table and closing a drawer. Stroke participant results show that the joint angle error norm reduced by an average of 50.3% over 6 attempts at each task when assisted by FES. PMID:26947097

  13. 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. PMID:19286295

  14. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats

    PubMed Central

    Besio, W.G.; Makeyev, O.; Medvedev, A.; Gale, K.

    2013-01-01

    Purpose To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. Methods The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. Results In the case of the TFS treated group, after TFS, there was a significant (p = 0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p = 0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p= 0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. Conclusions TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced towards the baseline. The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. PMID:23290195

  15. Mechanisms of deep brain stimulation.

    PubMed

    Herrington, Todd M; Cheng, Jennifer J; Eskandar, Emad N

    2016-01-01

    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

  16. Deep brain stimulation and the ethics of protection and caring for the patient with Parkinson's dementia.

    PubMed

    Farris, Sierra; Ford, Paul; DeMarco, Joseph; Giroux, Monique L

    2008-10-30

    Deep brain stimulation (DBS) is an effective neurosurgical treatment for patients with advanced Parkinson's disease (PD) suffering from motor complications that are refractory to further medication management. DBS requires an invasive procedure of implanting brain electrodes while awake, followed by implantation of neurostimulators under general anesthesia. The neurostimulator requires battery monitoring and replacement approximately every 3 to 5 years. These two elements of the technology provide numerous decision points about continuing therapies that can involve ethical choices. Although motor function can be improved with subthalamic nucleus (STN) DBS, the long-term risks of living with implanted hardware should be carefully evaluated for patients with diminishing cognitive capacity. We describe two cases where ethical dilemmas occurred postoperatively as a result of cognitive decline and describe salient ethical dimensions that illustrate the need for a proactive postoperative plan for supervision as a prerequisite for surgery to include neuropsychological testing to predict the likelihood of net benefit to the patient and family beyond just motor improvement. PMID:18759331

  17. Model-based analysis and design of nerve cuff electrodes for restoring bladder function by selective stimulation of the pudendal nerve

    NASA Astrophysics Data System (ADS)

    Kent, Alexander R.; Grill, Warren M.

    2013-06-01

    Objective. Electrical stimulation of the pudendal nerve (PN) is being developed as a means to restore bladder function in persons with spinal cord injury. A single nerve cuff electrode placed on the proximal PN trunk may enable selective stimulation of distinct fascicles to maintain continence or evoke micturition. The objective of this study was to design a nerve cuff that enabled selective stimulation of the PN. Approach. We evaluated the performance of both flat interface nerve electrode (FINE) cuff and round cuff designs, with a range of FINE cuff heights and number of contacts, as well as multiple contact orientations. This analysis was performed using a computational model, in which the nerve and fascicle cross-sectional positions from five human PN trunks were systematically reshaped within the nerve cuff. These cross-sections were used to create finite element models, with electric potentials calculated and applied to a cable model of a myelinated axon to evaluate stimulation selectivity for different PN targets. Subsequently, the model was coupled to a genetic algorithm (GA) to identify solutions that used multiple contact activation to maximize selectivity and minimize total stimulation voltage. Main results. Simulations did not identify any significant differences in selectivity between FINE and round cuffs, although the latter required smaller stimulation voltages for target activation due to preserved localization of targeted fascicle groups. Further, it was found that a ten contact nerve cuff generated sufficient selectivity for all PN targets, with the degree of selectivity dependent on the relative position of the target within the nerve. The GA identified solutions that increased fitness by 0.7-45.5% over single contact activation by decreasing stimulation of non-targeted fascicles. Significance. This study suggests that using an optimal nerve cuff design and multiple contact activation could enable selective stimulation of the human PN trunk for restoration of bladder function.

  18. Deep brain stimulation effects on memory.

    PubMed

    Laxton, A W; Sankar, T; Lozano, A M; Hamani, C

    2012-12-01

    As the population of many countries ages, disorders of cognition and memory-such as Alzheimer's Disease (AD) and dementia associated with Parkinson's Disease-will become a major societal burden. At present, few effective medical therapies against these conditions are available. Deep brain stimulation (DBS) may be a potential therapeutic option, because it can directly target and modulate the activity of structures implicated in circuits subserving memory function. In this article, we review the scientific literature to address some of the mechanisms by which DBS may impact memory and cognition. We then summarize the results of recent clinical experience with DBS in AD and Parkinsonian dementia. PMID:23111294

  19. 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. PMID:25983689

  20. 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

  1. Role of adenosine in the antiepileptic effects of deep brain stimulation.

    PubMed

    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

  2. The phenomenology of deep brain stimulation-induced changes in OCD: an enactive affordance-based model

    PubMed Central

    de Haan, Sanneke; Rietveld, Erik; Stokhof, Martin; Denys, Damiaan

    2013-01-01

    People suffering from Obsessive-Compulsive Disorder (OCD) do things they do not want to do, and/or they think things they do not want to think. In about 10% of OCD patients, none of the available treatment options is effective. A small group of these patients is currently being treated with deep brain stimulation (DBS). DBS involves the implantation of electrodes in the brain. These electrodes give a continuous electrical pulse to the brain area in which they are implanted. It turns out that patients may experience profound changes as a result of DBS treatment. It is not just the symptoms that change; patients rather seem to experience a different way of being in the world. These global effects are insufficiently captured by traditional psychiatric scales, which mainly consist of behavioral measures of the severity of the symptoms. In this article we aim to capture the changes in the patients' phenomenology and make sense of the broad range of changes they report. For that we introduce an enactive, affordance-based model that fleshes out the dynamic interactions between person and world in four aspects. The first aspect is the patients' experience of the world. We propose to specify the patients' world in terms of a field of affordances, with the three dimensions of broadness of scope (width of the field), temporal horizon (depth), and relevance of the perceived affordances (height). The second aspect is the person-side of the interaction, that is, the patients' self-experience, notably their moods and feelings. Thirdly, we point to the different characteristics of the way in which patients relate to the world. And lastly, the existential stance refers to the stance that patients take toward the changes they experience: the second-order evaluative relation to their interactions and themselves. With our model we intend to specify the notion of being in the world in order to do justice to the phenomenological effects of DBS treatment. PMID:24133438

  3. Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation

    PubMed Central

    Etiévant, A.; Oosterhof, C.; Bétry, C.; Abrial, E.; Novo-Perez, M.; Rovera, R.; Scarna, H.; Devader, C.; Mazella, J.; Wegener, G.; Sánchez, C.; Dkhissi-Benyahya, O.; Gronfier, C.; Coizet, V.; Beaulieu, J.M.; Blier, P.; Lucas, G.; Haddjeri, N.

    2015-01-01

    Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K+ buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal–glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders. PMID:26425697

  4. Stimulator system

    SciTech Connect

    Hakansson, B.H.; Saario, R.A.

    1984-02-14

    An electrical stimulator system is described incorporating rechargeable batteries and a charging circuit. A charging set and electrode support are alternatively connected to the stimulator system via a single common two-pole terminal. The system is designed to prevent current from flowing directly from the battery to the electrode support along the charging circuit while allowing charge current to flow in the opposite direction along the charging circuit if the charging set is connected to the system instead of the electrode support.

  5. The influence of electrolyte composition on the in vitro charge-injection limits of activated iridium oxide (AIROF) stimulation electrodes

    NASA Astrophysics Data System (ADS)

    Cogan, Stuart F.; Troyk, Philip R.; Ehrlich, Julia; Gasbarro, Christina M.; Plante, Timothy D.

    2007-06-01

    The effects of ionic conductivity and buffer concentration of electrolytes used for in vitro measurement of the charge-injection limits of activated iridium oxide (AIROF) neural stimulation electrodes have been investigated. Charge-injection limits of AIROF microelectrodes were measured in saline with a range of phosphate buffer concentrations from [PO43-] = 0 to [PO43-] = 103 mM and ionic conductivities from 2-28 mS cm-1. The charge-injection limits were insensitive to the buffer concentration, but varied significantly with ionic conductivity. Using 0.4 ms cathodal current pulses at 50 Hz, the charge-injection limit increased from 0.5 mC cm-2 to 2.1 mC cm-2 as the conductivity was increased from 2 mS cm-1 to 28 mS cm-1. An explanation is proposed in which the observed dependence on ionic conductivity arises from non-uniform reduction and oxidation within the porous AIROF and from uncorrected iR-drops that result in an overestimation of the redox potential during pulsing. Conversely, slow-sweep-rate cyclic voltammograms (CVs) were sensitive to buffer concentration with the potentials of the primary Ir3+/Ir4+ reduction and oxidation reactions shifting ~300 mV as the buffer concentration decreased from [PO43-] = 103 mM to [PO43-] = 0 mM. The CV response was insensitive to ionic conductivity. A comparison of in vitro AIROF charge-injection limits in commonly employed electrolyte models of extracellular fluid revealed a significant dependence on the electrolyte, with more than a factor of 4 difference under some pulsing conditions, emphasizing the need to select an electrolyte model that closely matches the conductivity and ionic composition of the in vivo environment.

  6. Disparities in deep brain stimulation surgery among insured elders with Parkinson disease

    PubMed Central

    Schootman, Mario; Kung, Nathan; Wang, Xiao-Yu; Perlmutter, Joel S.; Racette, Brad A.

    2014-01-01

    Objective: To identify sociodemographic, clinical, and physician/practice factors associated with deep brain stimulation (DBS). DBS is a proven surgical therapy for Parkinson disease (PD), but is recommended only for patients with excellent health, results in significant out-of-pocket costs, and requires substantial physician involvement. Methods: Retrospective cohort study of more than 657,000 Medicare beneficiaries with PD. Multivariable logistic regression models examined the association between demographic, clinical, socioeconomic status (SES), and physician/practice factors, and DBS therapy. Results: There were significant disparities in the use of DBS therapy among Medicare beneficiaries with PD. The greatest disparities were associated with race: black (adjusted odds ratio [AOR] 0.20, 95% confidence interval [CI] 0.160.25) and Asian (AOR 0.55, 95% CI 0.440.70) beneficiaries were considerably less likely to receive DBS than white beneficiaries. Women (AOR 0.79, 95% CI 0.750.83) also had lower odds of receiving DBS compared with men. Eighteen percent of procedures were performed on patients with PD who had cognitive impairment/dementia, a reported contraindication to DBS. Beneficiaries treated in minority-serving PD practices were less likely to receive DBS, regardless of individual race (AOR 0.76, 95% CI 0.660.87). Even after adjustment for demographic and clinical covariates, high neighborhood SES was associated with 1.4-fold higher odds of receiving DBS (AOR 1.42, 95% CI 1.331.53). Conclusions: Among elderly Medicare beneficiaries with PD, race, sex, and neighborhood SES are strong independent predictors of DBS receipt. Racial disparities are amplified when adjusting for physician/clinic characteristics. Future investigations of the demographic differences in clinical need/usefulness of DBS, ease of DBS attainment, and actual/opportunity DBS costs are needed to inform policies to reduce DBS disparities and improve PD quality of care. PMID:24336138

  7. 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

  8. Nonmotor Symptoms and Subthalamic Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Kim, Han-Joon; Jeon, Beom S.; Paek, Sun Ha

    2015-01-01

    Subthalamic deep brain stimulation (STN DBS) is an established treatment for the motor symptoms in patients with advanced Parkinson’s disease (PD). In addition to improvements in motor symptoms, many studies have reported changes in various nonmotor symptoms (NMSs) after STN DBS in patients with PD. Psychiatric symptoms, including depression, apathy, anxiety, and impulsivity, can worsen or improve depending on the electrical stimulation parameters, the locations of the stimulating contacts within the STN, and changes in medications after surgery. Global cognitive function is not affected by STN DBS, and there is no increase in the incidence of dementia after STN DBS compared to that after medical treatment, although clinically insignificant declines in verbal fluency have been consistently reported. Pain, especially PD-related pain, improves with STN DBS. Evidence regarding the effects of STN DBS on autonomic symptoms and sleep-related problems is limited and remains conflicting. Many symptoms of nonmotor fluctuations, which are occasionally more troublesome than motor fluctuations, improve with STN DBS. Although it is clear that NMSs are not target symptoms for STN DBS, NMSs have a strong influence on the quality of life of patients with PD, and clinicians should thus be aware of these NMSs when deciding whether to perform surgery and should pay attention to changes in these symptoms after STN DBS to ensure the optimal care for patients. PMID:26090080

  9. 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). PMID:26180680

  10. Deep brain stimulation: new directions.

    PubMed

    Ostergard, T; Miller, J P

    2014-12-01

    The role of deep brain stimulation (DBS) in the treatment of movement disorders is well established, but there has recently been a proliferation of additional indications that have been shown to be amenable to this technology. The combination of innovative approaches to neural interface technology with novel target identification based on previously discovered clinical effects of lesioning procedures has led to a fundamental paradigm for new directions in the application of DBS. The historical use of neurosurgical lesioning procedures in the treatment of psychiatric diseases such as obsessive compulsive disorder provided an initial opportunity to expand the use of DBS. The list is rapidly expanding and now includes major depressive disorder, Tourette's syndrome, addiction disorders, and eating disorders. Keen observations by neurosurgeons using these devices have lead to the incidental discovery of treatments for diseases without previous neurosurgical treatments. These discoveries are breaking new ground in the treatment of disorders of cognition, headache syndromes, disorders of consciousness, and epilepsy. Two features of DBS make it well-suited for treatment of disorders of nervous system function. First, the reversible, non-lesional nature of DBS allows for investigation of new targets without the morbidity of permanent side effects. Second, the programmable nature of DBS allows practitioners to alter stimulation patterns to minimize side effects and potentially improve efficacy through reprogramming. More importantly, proper scientific evaluation of new targets is aided by the ability to turn stimulation on and off with evaluators blinded to the stimulation status. Knowledge of these emerging therapies is important for practitioners, as there are many situations where a single target can effectively treat the symptoms of more than one disease. The intersection of advances in neuromodulation, neurophysiology, neuroimaging, and functional neuroanatomy has created an environment rife with new therapeutic possibilities. PMID:25418273

  11. 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. PMID:20955718

  12. Controlling stimulation strength and focality in electroconvulsive therapy via current amplitude and electrode size and spacing: comparison with magnetic seizure therapy

    PubMed Central

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2013-01-01

    Objectives Understanding the relationship between the stimulus parameters of electroconvulsive therapy (ECT) and the electric field characteristics could guide studies on improving risk/benefit ratio. We aim to determine the effect of current amplitude and electrode size and spacing on the ECT electric field characteristics, compare ECT focality with magnetic seizure therapy (MST), and evaluate stimulus individualization by current amplitude adjustment. Methods ECT and double-cone-coil MST electric field was simulated in a 5-shell spherical human head model. A range of ECT electrode diameters (25 cm), spacing (125 cm), and current amplitudes (0900 mA) were explored. The head model parameters were varied to examine the stimulus current adjustment required to compensate for interindividual anatomical differences. Results By reducing the electrode size, spacing, and current, the ECT electric field can be more focal and superficial without increasing scalp current density. By appropriately adjusting the electrode configuration and current, the ECT electric field characteristics can be made to approximate those of MST within 15%. Most electric field characteristics in ECT are more sensitive to head anatomy variation than in MST, especially for close electrode spacing. Nevertheless, ECT current amplitude adjustment of less than 70% can compensate for interindividual anatomical variability. Conclusions The strength and focality of ECT can be varied over a wide range by adjusting the electrode size, spacing, and current. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Current amplitude individualization can compensate for interindividual anatomical variability. PMID:24263276

  13. 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.

  14. High-Frequency Stimulation of the Rat Entopeduncular Nucleus Does Not Provide Functional or Morphological Neuroprotection from 6-Hydroxydopamine

    PubMed Central

    Fischer, D. Luke; Collier, Timothy J.; Cole-Strauss, Allyson; Wohlgenant, Susan L.; Lipton, Jack W.; Steece-Collier, Kathy; Manfredsson, Fredric P.; Kemp, Christopher J.; Sortwell, Caryl E.

    2015-01-01

    Deep brain stimulation (DBS) is the most common neurosurgical treatment for Parkinson’s disease (PD). Whereas the globus pallidus interna (GPi) has been less commonly targeted than the subthalamic nucleus (STN), a recent clinical trial suggests that GPi DBS may provide better outcomes for patients with psychiatric comorbidities. Several laboratories have demonstrated that DBS of the STN provides neuroprotection of substantia nigra pars compacta (SNpc) dopamine neurons in preclinical neurotoxin models of PD and increases brain-derived neurotrophic factor (BDNF). However, whether DBS of the entopeduncular nucleus (EP), the homologous structure to the GPi in the rat, has similar neuroprotective potential in preclinical models has not been investigated. We investigated the impact of EP DBS on forelimb use asymmetry and SNpc degeneration induced by 6-hydroxydopamine (6-OHDA) and on BDNF levels. EP DBS in male rats received unilateral, intrastriatal 6-OHDA and ACTIVE or INACTIVE stimulation continuously for two weeks. Outcome measures included quantification of contralateral forelimb use, stereological assessment of SNpc neurons and BDNF levels. EP DBS 1) did not ameliorate forelimb impairments induced by 6-OHDA, 2) did not provide neuroprotection for SNpc neurons and 3) did not significantly increase BDNF levels in any of the structures examined. These results are in sharp contrast to the functional improvement, neuroprotection and BDNF-enhancing effects of STN DBS under identical experimental parameters in the rat. The lack of functional response to EP DBS suggests that stimulation of the rat EP may not represent an accurate model of clinical GPi stimulation. PMID:26222442

  15. 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.

  16. Differential and better response to deep brain stimulation of chorea compared to dystonia in Huntington's disease.

    PubMed

    Velez-Lago, Frances M; Thompson, Amanda; Oyama, Genko; Hardwick, Angela; Sporrer, Justin M; Zeilman, Pamela; Foote, Kelly D; Bowers, Dawn; Ward, Herbert E; Sanchez-Ramos, Juan; Okun, Michael S

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant and progressive neurodegenerative syndrome characterized by motor, cognitive and psychiatric manifestations. Chorea and dystonia are features that may be troublesome to some patients and may potentially prove unresponsive to pharmacological treatments. There are several reports on the results of globus pallidus internus deep brain stimulation (DBS) surgery for HD. In these published cases, DBS was utilized mainly to treat disabling chorea. We report our experience with 2 HD cases treated with DBS. The cases illustrate a differential response with a better outcome in the choreic presentation compared to the dystonic presentation. Additionally, DBS worsened gait features in both cases. PMID:23343665

  17. Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats.

    PubMed

    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

  18. "Rescue" of bilateral subthalamic stimulation by bilateral pallidal stimulation: case report.

    PubMed

    Matias, Caio M; Silva, Danilo; Machado, Andre G; Cooper, Scott E

    2016-02-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) orglobus pallidus pars interna (GPi) is well established as a treatment for advanced Parkinson's disease. In general, one of the 2 targets is chosen based on the clinical features of each patient. Stimulation of both targets could be viewed as redundant, given that the 2 targets are directly connected. However, it is possible that each target has different mechanisms, with clinical effects mediated by orthodromic or antidromic stimulation. The authors report the case of a patient with severe Parkinson's disease who had previously undergone bilateral subthalamic stimulation with excellent benefits. However, he presented with significant worsening associated with disease progression and pharmacological treatment, and then underwent bilateral GPi DBS. Follow-up assessment was conducted clinically as well as through blinded ratings of video recordings. Pallidal DBS may be a safe and useful strategy to manage dystonic features and behavioral complications of subthalamic stimulation and pharmacological management. While combined stimulation was quite successful in the reported patient, further studies with larger samples and longer follow-up periods will be necessary before recommending the addition of pallidal DBS as a routine strategy for patients previously implanted with STN DBS. PMID:26230477

  19. New targets for deep brain stimulation treatment of Parkinson's disease.

    PubMed

    Castrioto, Anna; Moro, Elena

    2013-12-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) has been shown to be an effective treatment for patients with Parkinson's disease. Strong clinical evidence supports the improvement of motor and non-motor complications and quality of life, with some data suggesting that GPi DBS might be less effective than STN DBS. However, neither STN nor GPi stimulation provides a satisfactory control of non-dopaminergic symptoms, such as gait and balance impairment and cognitive decline, which are frequent and disabling symptoms in advanced Parkinson's disease patients. Therefore, several efforts have been made to discover alternative and new targets to overcome these current DBS limitations. Among these new targets, the stimulation of the pedunculopontine nucleus has initially appeared encouraging. However, findings from different double-blind trials have mitigated the enthusiasm. A multi-target strategy aimed at improving symptoms with different pathogenetic mechanisms might be a promising approach in the next years. PMID:24215284

  20. Deep brain stimulation in Huntington's disease: assessment of potential targets.

    PubMed

    Sharma, Mayur; Deogaonkar, Milind

    2015-05-01

    Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder that has very few effective therapeutic interventions. Since the disease has a defined neural circuitry abnormality, neuromodulation could be an option. Case reports, original research, and animal model studies were selected from the databases of Medline and PubMed. All related studies published up to July 2014 were included in this review. The following search terms were used: "Deep brain stimulation," "DBS," "thalamotomy," "pallidal stimulation," and "Huntington's Disease," "HD," "chorea," or "hyperkinetic movement disorders." This review examines potential nodes in the HD circuitry that could be modulated using deep brain stimulation (DBS) therapy. With rapid evolution of imaging and ability to reach difficult targets in the brain with refined DBS technology, some phenotypes of HD could potentially be treated with DBS in the near future. Further clinical studies are warranted to validate the efficacy of neuromodulation and to determine the most optimal target for HD. PMID:25698541

  1. History, applications, and mechanisms of deep brain stimulation.

    PubMed

    Miocinovic, Svjetlana; Somayajula, Suvarchala; Chitnis, Shilpa; Vitek, Jerrold L

    2013-02-01

    Deep brain stimulation (DBS) is an effective surgical treatment for medication-refractory hypokinetic and hyperkinetic movement disorders, and it is being explored for a variety of other neurological and psychiatric diseases. Deep brain stimulation has been Food and Drug Administration-approved for essential tremor and Parkinson disease and has a humanitarian device exemption for dystonia and obsessive-compulsive disorder. Neurostimulation is the fruit of decades of both technical and scientific advances in the field of basic neuroscience and functional neurosurgery. Despite the clinical success of DBS, the therapeutic mechanism of DBS remains under debate. Our objective is to provide a comprehensive review of DBS focusing on movement disorders, including the historical evolution of the technique, applications and outcomes with an overview of the most pertinent literature, current views on mechanisms of stimulation, and description of hardware and programming techniques. We conclude with a discussion of future developments in neurostimulation. PMID:23407652

  2. 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…

  3. 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

  4. 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…

  5. Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder.

    PubMed

    Kohl, S; Gruendler, T O J; Huys, D; Sildatke, E; Dembek, T A; Hellmich, M; Vorderwulbecke, M; Timmermann, L; Ahmari, S E; Klosterkoetter, J; Jessen, F; Sturm, V; Visser-Vandewalle, V; Kuhn, J

    2015-01-01

    Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200?ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation. PMID:26556284

  6. Axonal failure during high frequency stimulation of rat subthalamic nucleus

    PubMed Central

    Zheng, Fang; Lammert, Katja; Nixdorf-Bergweiler, Barbara E; Steigerwald, Frank; Volkmann, Jens; Alzheimer, Christian

    2011-01-01

    Abstract Deep brain stimulation (DBS) has been established as an effective surgical therapy for advanced Parkinson's disease (PD) and gains increasing acceptance for otherwise intractable neuropsychiatric diseases such as major depression or obsessivecompulsive disorders. In PD, DBS targets predominantly the subthalamic nucleus (STN) and relieves motor deficits only at high frequency (>100 Hz). In contrast to the well-documented clinical efficacy of DBS, its underlying principle remains enigmatic spawning a broad and, in part, contradictory spectrum of suggested synaptic and non-synaptic mechanisms within and outside STN. Here we focused on a crucial, but largely neglected issue in this controversy, namely the axonal propagation of DBS within and away from STN. In rat brain slices preserving STN projections to substantia nigra (SN) and entopeduncular nucleus (EP, the rodent equivalent of internal globus pallidus), STN-DBS disrupted synaptic excitation onto target neurons through an unexpected failure of axonal signalling. The rapid onset and, upon termination of DBS, recovery of this effect was highly reminiscent of the time course of DBS in the clinical setting. We propose that DBS-induced suppression of axonal projections from and to STN serves to shield basal ganglia circuitry from pathological activity arising in or amplified by this nucleus. PMID:21486784

  7. 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.

  8. 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 studys 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

  9. 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. PMID:26119240

  10. Update on deep brain stimulation.

    PubMed

    Greenberg, Benjamin D

    2002-12-01

    Deep brain stimulation (DBS) is an established therapy for movement disorders and an investigational treatment in other neurologic conditions and in neuropsychiatry. DBS can target with precision neuroanatomical targets deep within the brain that are proposed, on the basis of increasing evidence from functional neuroimaging and other methods, to be centrally involved in the pathophysiology of some neuropsychiatric illnesses. DBS is nonablative, offering the advantages of reversibility and adjustability. In theory, this characteristic might permit therapeutic effectiveness to be enhanced or side effects to be minimized. Although its mechanisms of action are unknown, several possible effects have been proposed to underlie the therapeutic effects of DBS in movement disorders, and potentially in other conditions as well. This issue is the subject of very active investigation in a number of clinical and preclinical laboratories. DBS may offer a degree of hope for patients with intractable neuropsychiatric illness. Research intended to realize this potential will require a very considerable commitment of resources, energy, and time across disciplines including psychiatry, neurosurgery, neurology, neuropsychology, and bioethics. Investigations in this area should proceed cautiously. PMID:12468994

  11. No Impact of Deep Brain Stimulation on Fear-Potentiated Startle in ObsessiveCompulsive Disorder

    PubMed Central

    Baas, Johanna M. P.; Klumpers, Floris; Mantione, Mariska H.; Figee, Martijn; Vulink, Nienke C.; Schuurman, P. Richard; Mazaheri, Ali; Denys, Damiaan

    2014-01-01

    Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessivecompulsive disorder (OCD). Given the close proximity of the stimulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS could be the result of the modulation of contextual anxiety. However, the effect of DBS in this region on contextual anxiety is as of yet unknown. Thus, the current study investigated the effect of DBS on contextual anxiety in an experimental threat of shock paradigm. Eight patients with DBS treatment for severe OCD were tested in a double-blind crossover design with randomly assigned 2-week periods of active and sham stimulation. DBS resulted in significant decrease of obsessivecompulsive symptoms, anxiety, and depression. However, even though the threat manipulation resulted in a clear context-potentiated startle effect, none of the parameters derived from the startle recordings was modulated by the DBS. This suggests that DBS in the ventral internal capsule is effective in treating anxiety symptoms of OCD without modulating the startle circuitry. We hypothesize that the anxiety symptoms present in OCD are likely distinct from the pathological brain circuits in defensive states of other anxiety disorders. PMID:25249953

  12. 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 (180Hz at 100μA) 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. PMID:26917269

  13. Sudden loss of the deep brain stimulation effect with high impedance without macroscopic fracture: a case report and review of the published literature.

    PubMed

    Yang, Hui-Jun; Yun, Ji Young; Kim, Young Eun; Lim, Yong Hoon; Kim, Han-Joon; Paek, Sun Ha; Jeon, Beom S

    2015-01-01

    The number of deep brain stimulation (DBS) hardware complications has increased during the past decade. In cases of abnormally high lead impedance with no evidence of a macroscopic fracture, optimal treatment options have not yet been established. Here, we present the case of a 49-year-old woman with a 12-year history of Parkinson's disease who received bilateral subthalamic nucleus DBS in March 2006. The patient showed good control of parkinsonism until December 24, 2010, when she awoke with abrupt worsening of parkinsonian symptoms. At telemetric testing, lead impedances were found at >2,000 ? in all four leads on the left side. Fracture of a lead or an extension wire was suspected. However, radiological screening and palpation revealed no macroscopic fracture. In June 2011, the implantable pulse generator (IPG) was changed under local anesthesia without any complications. Postoperatively, her parkinsonism immediately improved to the previous level, and the lead impedance readings by telemetry were also normalized. The disconnection of the neurostimulator connector block and the hybrid circuit board of the IPG was confirmed by destructive analysis. The present report illustrates that a staged approach that starts with simple IPG replacement can be an option for some cases of acute DBS effect loss with high impedance, when radiological findings are normal, thereby sparing the intact electrodes and extension wires. PMID:26229475

  14. Sudden loss of the deep brain stimulation effect with high impedance without macroscopic fracture: a case report and review of the published literature

    PubMed Central

    Yang, Hui-Jun; Yun, Ji Young; Kim, Young Eun; Lim, Yong Hoon; Kim, Han-Joon; Paek, Sun Ha; Jeon, Beom S

    2015-01-01

    The number of deep brain stimulation (DBS) hardware complications has increased during the past decade. In cases of abnormally high lead impedance with no evidence of a macroscopic fracture, optimal treatment options have not yet been established. Here, we present the case of a 49-year-old woman with a 12-year history of Parkinsons disease who received bilateral subthalamic nucleus DBS in March 2006. The patient showed good control of parkinsonism until December 24, 2010, when she awoke with abrupt worsening of parkinsonian symptoms. At telemetric testing, lead impedances were found at >2,000 ? in all four leads on the left side. Fracture of a lead or an extension wire was suspected. However, radiological screening and palpation revealed no macroscopic fracture. In June 2011, the implantable pulse generator (IPG) was changed under local anesthesia without any complications. Postoperatively, her parkinsonism immediately improved to the previous level, and the lead impedance readings by telemetry were also normalized. The disconnection of the neurostimulator connector block and the hybrid circuit board of the IPG was confirmed by destructive analysis. The present report illustrates that a staged approach that starts with simple IPG replacement can be an option for some cases of acute DBS effect loss with high impedance, when radiological findings are normal, thereby sparing the intact electrodes and extension wires. PMID:26229475

  15. Spatiotemporal dynamics of cortical perfusion in response to thalamic deep brain stimulation.

    PubMed

    Noor, M Sohail; Murari, Kartikeya; McCracken, Clinton B; Kiss, Zelma H T

    2016-02-01

    Deep brain stimulation (DBS) has revolutionized the treatment of movement disorders. The parameters of electrical stimulation are important to its therapeutic effect and remain a source of clinical controversy. DBS exerts its actions not only locally at the site of stimulation but also remotely through afferent and efferent connections, which are vital to its clinical effects. Yet, only a few studies have examined how cortical activity changes in response to various electrical parameters. Here, we investigated how the parameters of thalamic DBS alter cortical perfusion in rats using intrinsic optical imaging. We hypothesized that thalamic DBS will increase perfusion in primary motor cortex (M1), proportional to amplitude, pulse width, or frequency of the stimulation applied. We applied 45 different combinations of amplitude, pulse width and frequency in the ventro-lateral (VL) nucleus of the thalamus in anesthetized rats while measuring perfusion in M1. VL thalamic DBS reduced cortical reflectance, which corresponds to an increase in cortical perfusion. We computed the maximum change in reflectance (MCR) as well as the spatial spread of MCR in each trial. Both MCR and spatial spread increased linearly with increases in current amplitude or pulse width of stimulation; however, the effect of frequency was non-linear. Stimulation at 20Hz was significantly different from that at higher frequencies while stimulation at higher frequencies did not differ significantly from each other. Moreover, the effect of pulse width on MCR was larger than the effect of amplitude. The proportional increase in M1 perfusion due to increase in amplitude or pulse width suggests that both activate more neural elements and increase the volume of tissue activated. These results should help clinicians set parameters of DBS. The use of optical imaging to monitor effects of DBS on M1 may not only help understand DBS mechanisms, but may also provide feedback for closed loop DBS devices. PMID:26578359

  16. 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. PMID:25652752

  17. Deep brain stimulation in dementia-related disorders.

    PubMed

    Hescham, Sarah; Lim, Lee Wei; Jahanshahi, Ali; Blokland, Arjan; Temel, Yasin

    2013-12-01

    Memory loss is the key symptom of dementia-related disorders, including the prevalent Alzheimer's disease (AD). To date, pharmacological treatments for AD have limited and short-lasting effects. Therefore, researchers are investigating novel therapies such as deep brain stimulation (DBS) to treat memory impairment and to reduce or stop the progression of it. Clinical and preclinical studies have been performed and stimulations of the fornix, entorhinal cortex and nucleus basalis of Meynert have been carried out. The results of these studies suggest that DBS has the potential to enhance memory functions in patients and animal models. The mechanisms underlying memory enhancement may include the release of specific neurotransmitters and neuroplasticity. Some authors suggest that DBS might even be disease-modifying. Nevertheless, it is still premature to conclude that DBS can be used in the treatment of AD, and the field will wait for the results of ongoing clinical trials. PMID:24060532

  18. Surface modification of neural stimulating/recording electrodes with high surface area platinum-iridium alloy coatings.

    PubMed

    Petrossians, Artin; Whalen, John J; Weiland, James D; Mansfeld, Florian

    2011-01-01

    High-surface area platinum-iridium alloys were electrodeposited by on Pt and Au microelectrodes using a potential sweep technique. Detailed investigations of the structure and morphology and the electrochemical properties of the electrodeposited Pt-Ir alloy coatings were performed. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used for the determination of the surface morphology and the chemical composition of the Pt-Ir coatings, respectively. The elemental analysis by EDS showed a nearly 60-40% Pt-Ir composition of the coatings. The electrochemical properties of the Pt-Ir coatings were evaluated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). CV and EIS measurements revealed that the Pt-Ir coated electrodes exhibit significantly increased charge storage capacity and real surface area compared to uncoated Pt electrodes. Charge injection experiments of the Pt-Ir coated microelectrodes revealed low potential excursions, indicating high charge injection capabilities within safe potential limits. PMID:22254972

  19. 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.

  20. Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

    PubMed Central

    Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

    2015-01-01

    Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation. PMID:25897892

  1. Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

    PubMed

    Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

    2015-01-01

    Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation. PMID:25897892

  2. Post subthalamic area deep brain stimulation for tremors: a mini-review

    PubMed Central

    2012-01-01

    Deep brain stimulation (DBS) in the thalamic ventrointermediate nucleus (VIM) is the traditional target for the surgical treatment of pharmacologically refractory essential tremor or parkinsonian tremor. Studies in recent years on DBS in posterior subthalamic area (PSA), including the zona incerta and the prelemniscal radiation, have shown promising results in tremor suppression, particularly for those tremors difficult to be well controlled by VIM DBS, such as the proximal postural tremor, distal intention tremor and some cerebellar outflow tremor in various diseases including essential tremor and multiple sclerosis. The adverse effect profile of the PSA DBS is mild and transient, without lasting or striking dysarthria, disequilibrium or tolerance, in contrast to VIM DBS, particularly bilateral DBS. However, the studies on PSA DBS so far are still limited, with a handful of studies on bilateral PSA, and a short follow up duration compared to VIM. More studies are needed for direct comparison of these targets in the future. A review here would help to gain more insight into the benefits and limits of the PSA DBS compared to that in VIM in the clinical management of various tremors, particularly for those difficult to be well controlled by traditional VIM DBS. PMID:23210767

  3. Catatonia After Deep Brain Stimulation Successfully Treated With Lorazepam and Right Unilateral Electroconvulsive Therapy: A Case Report

    PubMed Central

    Quinn, Davin K.; Rees, Caleb; Brodsky, Aaron; Deligtisch, Amanda; Evans, Daniel; Khafaja, Mohamad; Abbott, Christopher C.

    2013-01-01

    Objectives The presence of a deep brain stimulator (DBS) in a patient who develops neuropsychiatric symptoms poses unique diagnostic challenges and questions for the treating psychiatrist. Catatonia has been described only once, during DBS implantation, but has not been reported in a successfully implanted DBS patient. Materials/Methods We present a case of a patient with bipolar disorder and renal transplant who developed catatonia after DBS for essential tremor. Results The patient was successfully treated for catatonia with lorazepam and electroconvulsive therapy (ECT) after careful diagnostic workup. ECT has been successfully used with DBS in a handful of cases and certain precautions may help reduce potential risk. Conclusions Catatonia is a rare occurrence after DBS, but when present may be safely treated with standard therapies such as lorazepam and ECT. PMID:23859977

  4. Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation

    PubMed Central

    Schiefer, Terry K.; Matsumoto, Joseph Y.; Lee, Kendall H.

    2011-01-01

    The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinsons disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted. PMID:22084629

  5. Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

    ERIC Educational Resources Information Center

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

    2013-01-01

    Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

  6. Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

    ERIC Educational Resources Information Center

    Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

    2013-01-01

    Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight

  7. Globus Pallidus Interna Deep Brain Stimulation for Chorea-Acanthocytosis

    PubMed Central

    Lee, Jae-Hyeok; Cho, Won-Ho; Cha, Seung-Heon

    2015-01-01

    Chorea-acanthocytosis (ChAc) is a rare hereditary disorder characterized by involuntary choreiform movements and erythrocytic acanthocytosis. Pharmacotherapy for control of involuntary movements has generally been of limited benefit. Deep brain stimulation (DBS) has recently been used for treatment of some refractory cases of ChAc. We report here on the effect of bilateral high-frequency DBS of globus pallidus interna in a patient with ChAc. PMID:25733999

  8. Urinary incontinence following deep brain stimulation of the pedunculopontine nucleus.

    PubMed

    Aviles-Olmos, Iciar; Foltynie, Thomas; Panicker, Jalesh; Cowie, Dorothy; Limousin, Patricia; Hariz, Marwan; Fowler, Clare J; Zrinzo, Ludvic

    2011-12-01

    Low-frequency deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been reported to improve akinesia and gait difficulties in patients with Parkinson's disease (PD). We report on a patient with PD and L: -dopa refractory gait symptoms who developed detrusor over-activity immediately after right PPN DBS. Proximity between caudal PPN and brainstem structures implicated in control of micturition is a possible explanation. PMID:21927820

  9. Successful thalamic deep brain stimulation for orthostatic tremor.

    PubMed

    Guridi, Jorge; Rodriguez-Oroz, Maria C; Arbizu, Javier; Alegre, Manuel; Prieto, Elena; Landecho, Ignacio; Manrique, Miguel; Artieda, Julio; Obeso, Jose A

    2008-10-15

    We report a patient with severe orthostatic tremor (OT) unresponsive to pharmacological treatments that was successfully controlled with thalamic (Vim, ventralis intermedius nucleus) deep brain stimulation (DBS) over a 4-year period. Cortical activity associated with the OT revealed by EEG back-averaging and fluoro-deoxi-glucose PET were also suppressed in parallel with tremor arrest. This case suggests that Vim-DBS may be a useful therapeutic approach for patients highly disabled by OT. PMID:18671286

  10. Quadruple deep brain stimulation in Huntington's disease, targeting pallidum and subthalamic nucleus: case report and review of the literature.

    PubMed

    Gruber, D; Kuhn, A A; Schoenecker, T; Kopp, U A; Kivi, A; Huebl, J; Lobsien, E; Mueller, B; Schneider, G-H; Kupsch, A

    2014-10-01

    Deep brain stimulation (DBS) represents an established treatment option in a growing number of movement disorders. Recent case reports suggest beneficial effect of globus pallidus internus (GPi)-DBS in selected patients suffering from Huntington's disease with marked disabling chorea. We present a 41-year-old man with genetically confirmed HD following quadruple GPi- and subthalamic nucleus (STN)-DBS. Motor function was assessed by Abnormal Involuntary Movement Scale (AIMS) and by Unified Huntington Disease Rating Scale (UHDRS) presurgery and postsurgery for up to 4 years. Furthermore, cognitive, neuropsychiatric state and quality of life (QoL) including life satisfaction (QLS) were annually evaluated. Chorea assessed by AIMS and UHDRS subscores improved by 52 and 55 %, 45 and 60 %, 35 and 45 % and 55-66 % at 1-4 years, respectively, compared to presurgical state following GPi-STN-DBS. During these time periods bradykinesia did not increase following separate STN- and combined GPi-STN-DBS compared to presurgical state. Mood, QoL and QLS were ameliorated. However, dysexecutive symptoms increased at 4 years postsurgery. The present case report suggests that bilateral GPi- and STN-DBS may represent a new treatment avenue in selected HD patients. Clinically, GPi-DBS attenuated chorea and was associated with a larger effect-adverse effect window compared to STN-DBS. However, GPi-DBS-induced bradykinesia may emerge as one main limitation of GPi-DBS in HD. Thus, quadruple GPi-STN-DBS may be indicated, if separate GPi-DBS does not result in sufficient control of motor symptoms. Future controlled studies need to confirm if the present anecdotal observation of additive beneficial effects of GPi- and STN-DBS in a HD patient with severe generalized chorea and relatively intact cognitive and affective functions indeed represents a new therapeutic option. PMID:24699718

  11. Movement-Related Discharge in the Macaque Globus Pallidus during High-Frequency Stimulation of the Subthalamic Nucleus

    PubMed Central

    Zimnik, Andrew J.; Nora, Gerald J.; Desmurget, Michel

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an informational lesion, whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism. PMID:25740526

  12. Movement-related discharge in the macaque globus pallidus during high-frequency stimulation of the subthalamic nucleus.

    PubMed

    Zimnik, Andrew J; Nora, Gerald J; Desmurget, Michel; Turner, Robert S

    2015-03-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an "informational lesion," whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism. PMID:25740526

  13. 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.

  14. Deep Brain Stimulation for Parkinsons Disease and Other Movement Disorders

    PubMed Central

    2005-01-01

    Executive Summary Objective To determine the effectiveness and adverse effects of deep brain stimulation (DBS) in the treatment of symptoms of idiopathic Parkinsons disease, essential tremor, and primary dystonia and to do an economic analysis if evidence for effectiveness is established. The Technology Deep brain stimulation (DBS) is a surgical procedure indicated in the relief of motor function symptoms of Parkinsons disease, essential tremor and dystonia. It involves the surgical implantation of the DBS device, which include the implantable pulse generator or stimulator, the extension, and the lead. The electric impulse is produced within the stimulator component, and transmitted to the brain site by the extension and the lead(s). DBS surgery can be either unilateral or bilateral. The laterality of the surgery and target area for brain stimulation may vary with the type of symptom or spectrum of symptoms, and such decisions are made on a case-by-case basis. Advantages of DBS over ablative surgery is that it is comparatively less invasive, it is reversible, and it allows for stimulation of both sides of the brain. Ablative surgery, which is not practiced in Ontario, results in a non-reversible lesion and is often not conducted on both sides. Thus far, DBS has been considered as an adjunct to drug therapy. Review Strategy The standard Medical Advisory Secretariat search strategy was conducted to identify international health technology assessments and English language journal articles published from January 1, 2001 onwards. Documents were reviewed separately for Parkinsons disease, essential tremor and primary dystonia. Summary of Findings There is level 1b evidence that bilateral DBS of the subthalamic nucleus is effective in the short-term control of advanced parkinsonian symptoms, and there is level 3a evidence that the effect is sustained for at least 5 years. There is Level 3a evidence that DBS of the thalamus is effective in the control of tremor in patients with essential tremor and PD for at least 6 years. There is level 3a evidence that bilateral DBS of the globus pallidus is effective in the control of symptoms of primary dystonia for at least 1 year. Conclusion According to the estimates of prevalence and evidence of effectiveness, there is a shortfall in the numbers of DBS currently done in Ontario for drug-resistant PD, essential tremor, and primary dystonia. Since complication rates are lower if DBS is performed in specialized centres, the number of sites should be limited. The cost per procedure to institutions with the expertise to undertake DBS and the human resource considerations are likely to be limiting factors in the further diffusion of DBS. PMID:23074471

  15. Brain stimulation in posttraumatic stress disorder

    PubMed Central

    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 reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. PMID:22893803

  16. Current perspectives on deep brain stimulation for severe neurological and psychiatric disorders

    PubMed Central

    Kocabicak, Ersoy; Temel, Yasin; Höllig, Anke; Falkenburger, Björn; Tan, Sonny KH

    2015-01-01

    Deep brain stimulation (DBS) has become a well-accepted therapy to treat movement disorders, including Parkinson’s disease, essential tremor, and dystonia. Long-term follow-up studies have demonstrated sustained improvement in motor symptoms and quality of life. DBS offers the opportunity to selectively modulate the targeted brain regions and related networks. Moreover, stimulation can be adjusted according to individual patients’ demands, and stimulation is reversible. This has led to the introduction of DBS as a treatment for further neurological and psychiatric disorders and many clinical studies investigating the efficacy of stimulating various brain regions in order to alleviate severe neurological or psychiatric disorders including epilepsy, major depression, and obsessive–compulsive disorder. In this review, we provide an overview of accepted and experimental indications for DBS therapy and the corresponding anatomical targets. PMID:25914538

  17. Thinking Ahead on Deep Brain Stimulation: An Analysis of the Ethical Implications of a Developing Technology

    PubMed Central

    Johansson, Veronica; Garwicz, Martin; Kanje, Martin; Halldenius, Lena; Schouenborg, Jens

    2014-01-01

    Deep brain stimulation (DBS) is a developing technology. New generations of DBS technology are already in the pipeline, yet this particular fact has been largely ignored among ethicists interested in DBS. Focusing only on ethical concerns raised by the current DBS technology is, albeit necessary, not sufficient. Since current bioethical concerns raised by a specific technology could be quite different from the concerns it will raise a couple of years ahead, an ethical analysis should be sensitive to such alterations, or it could end up with results that soon become dated. The goal of this analysis is to address these changing bioethical concerns, to think ahead on upcoming and future DBS concerns both in terms of a changing technology and changing moral attitudes. By employing the distinction between inherent and noninherent bioethical concerns we identify and make explicit the particular limits and potentials for change within each category, respectively, including how present and upcoming bioethical concerns regarding DBS emerge and become obsolete. Many of the currently identified ethical problems with DBS, such as stimulation-induced mania, are a result of suboptimal technology. These challenges could be addressed by technical advances, while for instance perceptions of an altered body image caused by the mere awareness of having an implant may not. Other concerns will not emerge until the technology has become sophisticated enough for new uses to be realized, such as concerns on DBS for enhancement purposes. As a part of the present analysis, concerns regarding authenticity are used as an example. PMID:24587963

  18. Deep brain stimulation in ireland for Parkinson's disease and essential tremor.

    PubMed

    Mulroy, E; Quigley, G; Roberts, K; Cummins, G; Magennis, B; Fortune, G; O'Brien, D; Blunnie, W P; Harrington, E; Gillivan-Murphy, P; Kavanagh, E; Gilligan, P; Reilly, R; Scolaí, P O; Kelly, S; Murray, M; Lynch, T

    2012-09-01

    Deep brain stimulation (DBS) is highly effective neurosurgery for idiopathic Parkinson's disease (IPD), essential tremor (ET) and primary dystonia. DBS involves stereotactic surgical implantation of a battery-operated stimulator into deep brain nuclei. Irish patients are referred abroad for DBS and have to travel repeatedly for pre and post-operative care resulting in stress, anxiety and hardship. Safe pre and post-operative care of these complex, ageing patients is compromised by the absence of a DBS service in Ireland. Moreover, both DBS surgery and the subsequent post-operative care abroad incurs substantial cost to the state. The Dublin Neurological Institute at the Mater Misericordiae University Hospital (DNI) is a non-profit institute for the care of patients with neurological diseases. The DNI developed, in collaboration with the Mater Private Hospital (MPH) and the Walton Centre, Liverpool, a DBS programme in 2008/2009. We performed DBS at the Mater Campus on three carefully selected patients from a cohort of movement disorder patients attending the DNI and continue to provide pre-operative assessment and post operative care for patients following DBS in Ireland and abroad. PMID:23155918

  19. Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell

    PubMed Central

    Wilden, Jessica A.; Qing, Kurt Y.; Hauser, Sheketha R.; McBride, William J.; Irazoqui, Pedro P.; Rodd, Zachary A.

    2015-01-01

    Object There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. Methods In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of ?aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (810 rats/group), after which the animals were placed in operant chambers containing 2 leversone used to administer water and the other to administer 15% EtOHto examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rats left AcbSh. The animals then received 100 or 200 ?A (34 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. Results In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 ?A of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Conclusions Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism. PMID:24460492

  20. The psychiatric and neuropsychiatric symptoms after subthalamic stimulation for Parkinson's disease.

    PubMed

    Mosley, Philip E; Marsh, Rodney

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for the motor symptoms of Parkinson's disease (PD). Nonmotor features of PD, however, may not improve with STN DBS, and a specific constellation of neuropsychiatric symptoms may emerge in the postoperative period. Mania, impulsivity, depression, and apathy may curtail the potential gains from surgery. In this paper, the authors discuss surgical candidacy, postoperative management of neuropsychiatric issues, and clinical dilemmas for the psychiatrist at the DBS center. A paradigm that considers stimulation effects and dopamine replacement therapy to be key drivers of postoperative neuropsychiatric problems is presented. PMID:25716484

  1. Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease.

    PubMed

    Serranov, Tereza; Jech, Robert; Duek, Petr; Sieger, Tom; R?i?ka, Filip; Urgok, Duan; R?i?ka, Even

    2011-10-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age SD, 58.3 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty-four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS-related sensitivity to food reward stimuli cues might drive DBS-treated patients to higher food intake and subsequent weight gain. PMID:21780183

  2. 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 50?L), 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. 30?L 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 300?L methanol/acetonitrile mixture (1:1, v/v). After evaporation, redissolved in 100?L mobile phase of LC-MS/MS and 5?L 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). PMID:26255955

  3. DBS investigation on films of cobalt chloride doped PVA-PVP blend

    NASA Astrophysics Data System (ADS)

    Hammannavar, Preeti B.; Baraker, Basavarajeshwari M.; Bhajantri, R. F.; Ravindrachary, V.; Lobo, Blaise

    2015-06-01

    Films of Cobalt Chloride (CoCl2) doped polyvinylalcohol(PVA)- polyvinylpyrrolidone(PVP) blend (doped from 0.5 wt% up to 28 wt%) were prepared by solution casting, and characterized by XRD, DSC, UV-Visible Spectrometry TGA, FTIR and electrical measurements. In this paper, the results of Doppler Broadening Spectroscopy (DBS) in CoCl2 doped PVA-PVP blend is discussed. An increase in crystallinity of PVA-PVP blend, is observed, on doping it with CoCl2. The DBS results are complemented by XRD and DSC scans.

  4. Do Patient's Get Angrier Following STN, GPi, and Thalamic Deep Brain Stimulation

    PubMed Central

    Burdick, Adam P.; Foote, Kelly D.; Wu, Samuel; Bowers, Dawn; Zeilman, Pam; Jacobson, Charles E.; Ward, Herbert E.; Okun, Michael S.

    2010-01-01

    Objective The objective of the study was to examine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), the globus pallidus internus (GPi), and/or the ventralis intermedius thalamic nucleus (Vim) was associated with making patients angrier pre to post-surgical intervention. Background Secondary outcome analysis of the NIH COMPARE Parkinson's Disease DBS trial revealed that participants were angrier and had more mood and cognitive side effects following DBS. Additionally blinded on/off analysis did not change anger scores. The sample size was small but suggested that STN DBS may have been worse than GPi in provoking anger. We endeavored to examine this question utilizing a larger dataset (the UF INFORM database), and also we included a third surgical target (Vim) which has been utilized for a different disease, essential tremor. Methods Consecutive patients from the University of Florida Movement Disorders Center who were implanted with unilateral DBS for Parkinson's Disease (STN or GPi) or Essential Tremor (Vim) were included. Patients originally implanted at outside institutions were excluded. Pre- and 4-6 month postoperative Visual Analog Mood Scales (VAMS) scores for all three groups were compared; additionally, pre- and 1-3 month scores were compared for STN and GPi patients. A linear regression model was utilized to analyze the relationship between the VAMS anger score and the independent variables of age, years with symptoms, Mini-mental status examination (MMSE) score, handedness, ethnicity, gender, side of surgery, target of surgery, baseline Dementia Rating Scale (DRS) total score, baseline Beck Depression Index (BDI) score, micro and macro electrode passes, and years of education. Levodopa equivalent dosages and dopamine agonist use was analyzed for a potential impact on anger scores. Results A total of 322 unilateral DBS procedures were analyzed, with STN (n= 195), Vim (n=71), and GPi (n=56) making up the cohort. An ANOVA analysis was used to detect significant differences among the three targets in the changes pre- to post-operatively. Similar to the COMPARE dataset, at four months the only subscore of VAMS to reveal a significant difference between the three targets was the angry subscore, with GPi revealing a mean (standard) change of 2.38 (9.53), STN 4.82 (14.52), and Vim -1.17 (11.51) (p-value = 0.012). At 1-3 months postop, both STN and GPi groups were significantly angrier (p= 0.004), but there was no significant difference between the two groups. However, GPi patients were significantly more confused as compared to STN patients (p= 0.016). The linear regression model which sought independent explanatory variables revealed a relationship between the VAMS anger score and the surgical target and the disease duration. The mean changes for STN and GPi DBS pre- to post were 11.67 (p= 0.001) and 8.21 (p= 0.022) units more than those with Vim, respectively. For every year added of disease duration, the VAMS anger score increased by 0.24 (p= 0.022). For the GPi and STN groups, number of microelectrode passes was significantly associated with angry score changes (p= 0.014), with the anger score increasing 2.29 units per microelectrode pass. Independent variables not associated with the VAMS anger score included the surgery side, handedness, gender, ethnicity, education, age at surgery, MMSE, DRS, and BDI scores. Although the STN group significantly decreased in LED when compared to GPi, there was no relationship to anger scores. Similarly dopamine agonist use was not different between STN and GPi groups, and did not correlate with the VAMS anger score changes. Conclusions STN and GPi DBS for Parkinson's disease were associated with significantly higher anger scores pre- to post-DBS as compared to Vim for essential tremor. Anger score changes in STN and GPi patients seem to be associated with microelectrode passes, suggesting it may be a lesional effect. PD patients with longer disease durations may be particularly susceptible, and this should be kept in mind when discussing the potential of DBS surgery for an individual patient. Essential tremor patients who on average have much longer disease durations did not get angrier. The changes in anger scores were not related to LED change or dopamine agonist use. Whether the induction of anger is disease specific or target specific is not currently known, however our data would suggest that PD patients implanted in STN or GPi are at a potential risk. Finally, on closer inspection of the COMPARE DBS data VAMS anger scores did not change on or off DBS, suggesting that anger changes may be more a lesional effect rather than a stimulation induced one(Okun et al., 2009). PMID:20932923

  5. Evolution of Deep Brain Stimulation: Human Electrometer and Smart Devices Supporting the Next Generation of Therapy

    PubMed Central

    Lee, Kendall H.; Blaha, Charles D.; Garris, Paul A.; Mohseni, Pedram; Horne, April E.; Bennet, Kevin E.; Agnesi, Filippo; Bledsoe, Jonathan M.; Lester, Deranda B.; Kimble, Chris; Min, Hoon-Ki; Kim, Young-Bo; Cho, Zang-Hee

    2010-01-01

    Deep Brain Stimulation (DBS) provides therapeutic benefit for several neuropathologies including Parkinsons disease (PD), epilepsy, chronic pain, and depression. Despite well established clinical efficacy, the mechanism(s) of DBS remains poorly understood. In this review we begin by summarizing the current understanding of the DBS mechanism. Using this knowledge as a framework, we then explore a specific hypothesis regarding DBS of the subthalamic nucleus (STN) for the treatment of PD. This hypothesis states that therapeutic benefit is provided, at least in part, by activation of surviving nigrostriatal dopaminergic neurons, subsequent striatal dopamine release, and resumption of striatal target cell control by dopamine. While highly controversial, we present preliminary data that are consistent with specific predications testing this hypothesis. We additionally propose that developing new technologies, e.g., human electrometer and closed-loop smart devices, for monitoring dopaminergic neurotransmission during STN DBS will further advance this treatment approach. PMID:20657744

  6. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease

    PubMed Central

    de Hemptinne, Coralie; Swann, Nicole; Ostrem, Jill L.; Ryapolova-Webb, Elena S.; Luciano, Marta San; Galifianakis, Nicholas; Starr, Philip A.

    2015-01-01

    Deep brain stimulation (DBS) is increasingly applied to the treatment of brain disorders, but its mechanism of action remains unknown. Here, we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the ? rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive ? phase locking of motor cortex neurons. PMID:25867121

  7. Management and outcome of pallidal deep brain stimulation in severe Huntington's disease.

    PubMed

    Huys, D; Bartsch, C; Poppe, P; Lenartz, D; Huff, W; Prütting, J; Timmermann, L; Klosterkötter, J; Maarouf, M; Rommel, T; Hartmann, A; Sturm, V; Kuhn, J

    2013-04-01

    Neurodegenerative movement disorders, such as Huntington's disease (HD), have become a promising field for Deep Brain Stimulation (DBS). This study aims to contribute to the establishment of a well-grounded database including both expected and unexpected effects of pallidal DBS in HD, and to discuss the ethical and legal restrictions of DBS in cognitively limited patients. Evaluation of the outcome data indicates that pallidal DBS exerted an independent effect on motor symptoms but probably also on the patient's cognitive and affective state. The cognitive decline, however, that characterizes the late stage of neurodegenerative disorders implicates ethical and legal problems given the patients' inability to give informed consent to DBS. PMID:23589113

  8. Evolution of Deep Brain Stimulation: Human Electrometer and Smart Devices Supporting the Next Generation of Therapy.

    PubMed

    Lee, Kendall H; Blaha, Charles D; Garris, Paul A; Mohseni, Pedram; Horne, April E; Bennet, Kevin E; Agnesi, Filippo; Bledsoe, Jonathan M; Lester, Deranda B; Kimble, Chris; Min, Hoon-Ki; Kim, Young-Bo; Cho, Zang-Hee

    2009-04-01

    Deep Brain Stimulation (DBS) provides therapeutic benefit for several neuropathologies including Parkinson's disease (PD), epilepsy, chronic pain, and depression. Despite well established clinical efficacy, the mechanism(s) of DBS remains poorly understood. In this review we begin by summarizing the current understanding of the DBS mechanism. Using this knowledge as a framework, we then explore a specific hypothesis regarding DBS of the subthalamic nucleus (STN) for the treatment of PD. This hypothesis states that therapeutic benefit is provided, at least in part, by activation of surviving nigrostriatal dopaminergic neurons, subsequent striatal dopamine release, and resumption of striatal target cell control by dopamine. While highly controversial, we present preliminary data that are consistent with specific predications testing this hypothesis. We additionally propose that developing new technologies, e.g., human electrometer and closed-loop smart devices, for monitoring dopaminergic neurotransmission during STN DBS will further advance this treatment approach. PMID:20657744

  9. The change in cerebral glucose metabolism after electroacupuncture: a possible marker to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa

    PubMed Central

    Liu, Tao-Tao; Hong, Qing-Xiong; Xiang, Hong-Bing

    2015-01-01

    Some reports have demonstrated that deep brain stimulation (DBS) is a promising treatment for patients who suffer from intractable anorexia nervosa. However, the nature of DBS may not be viewed as a standard clinical treatment option for anorexia nervosa because of the unpredictable outcome before DBS. Just like DBS in the brain, electroacupuncture at acupoints is also efficient in treating refractory anorexia nervosa. Some neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) had revealed that both DBS and electroacupuncture at acupoints with electrical stimulation are related to the changes in cerebral glucose metabolism. Therefore, we hypothesize that the changes in cerebral glucose metabolism after electroacupuncture might be useful to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa. PMID:26770596

  10. Deep Brain Stimulation of the Human Reward System for Major DepressionRationale, Outcomes and Outlook

    PubMed Central

    Schlaepfer, Thomas E; Bewernick, Bettina H; Kayser, Sarah; Hurlemann, Rene; Coenen, Volker A

    2014-01-01

    Deep brain stimulation (DBS) as a putative approach for treatment-resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studiesall in relatively small patient populations and different target regionshave shown clinically relevant antidepressant effects in about half of the patients and very recently, DBS to a key structure of the reward system, the medial forebrain bundle, has yielded promising results within few days of stimulation and at much lower stimulation intensities. On the downside, DBS procedures in regions are associated with surgical risks (eg, hemorrhage) and psychiatric complications (suicidal attenuation, hypomania) as well as high costs. This overview summarizes research on the mechanisms of brain networks with respect to psychiatric diseases andas a noveltyextrapolates to the role of the reward system in DBS for patients with treatment-resistant depression. It further evaluates relevant methodological aspects of today's research in DBS for TRD. On the scientific side, the reward system has an important yet clearly under-recognized role in both neurobiology and treatment of depression. On the methodological side of DBS research in TRD, better animal models are clearly needed to explain clinical effects of DBS in TRD. Larger sample sizes, long-term follow-up and designs including blinded sham control are required to draw final conclusions on efficacy and side effects. Practical research issues cover study design, patient tracking, and the discussion of meaningful secondary outcome measures. PMID:24513970

  11. Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients.

    PubMed

    Wagenbreth, Caroline; Zaehle, Tino; Galazky, Imke; Voges, Jrgen; Guitart-Masip, Marc; Heinze, Hans-Jochen; Dzel, Emrah

    2015-06-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC. PMID:25929662

  12. Deep brain stimulation of globus pallidus interna, subthalamic nucleus, and pedunculopontine nucleus for Parkinson's disease: which target?

    PubMed

    Follett, Kenneth A; Torres-Russotto, Diego

    2012-01-01

    Deep brain stimulation (DBS) is an accepted therapy for people with Parkinson's disease (PD) motor symptoms that are refractory to pharmacologic therapy. Standard DBS targets are globus pallidus interna (GPi) and subthalamic nucleus (STN). The pedunculopontine nucleus (PPN) is being investigated as a novel target. Which target provides the best outcomes is unknown. The utility of GPi and STN as targets has been confirmed in numerous studies, including randomized comparisons of GPi DBS and STN DBS that demonstrated no difference in motor outcomes. DBS at either site improves appendicular motor symptoms, but beneficial effects on axial manifestations of PD such as postural instability or gait dysfunction (PIGD) are less apparent. PPN has been introduced as a DBS target due to failure of GPi and STN DBS to improve PIGD. Small observational studies indicate improved PIGD with PPN DBS, but small blinded trials show only subjective reduction in falls with no other impact on PIGD or other PD manifestations. No single DBS target is superior to the others. Each target offers relative advantages. Further studies are needed to better define the roles of each target, particularly PPN. Choice of target should be individualized according to providers' preferences and patients' needs. PMID:22166422

  13. Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation.

    PubMed

    Halpern, Casey H; Tekriwal, Anand; Santollo, Jessica; Keating, Jeffrey G; Wolf, John A; Daniels, Derek; Bale, Tracy L

    2013-04-24

    Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive-compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, whereas the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice and was found to acutely reduce caloric intake and induce weight loss. Together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system. PMID:23616522

  14. Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology.

    PubMed

    Ho, Allen L; Erickson-Direnzo, Elizabeth; Pendharkar, Arjun V; Sung, Chih-Kwang; Halpern, Casey H

    2015-06-01

    Tremulous voice is a characteristic feature of a multitude of movement disorders, but when it occurs in individuals diagnosed with essential tremor, it is referred to as essential vocal tremor (EVT). For individuals with EVT, their tremulous voice is associated with significant social embarrassment and in severe cases may result in the discontinuation of employment and hobbies. Management of EVT is extremely difficult, and current behavioral and medical interventions for vocal tremor result in suboptimal outcomes. Deep brain stimulation (DBS) has been proposed as a potential therapeutic avenue for EVT, but few studies can be identified that have systematically examined improvements in EVT following DBS. The authors describe a case of awake bilateral DBS targeting the ventral intermediate nucleus for a patient suffering from severe voice and arm tremor. They also present their comprehensive, multidisciplinary methodology for definitive treatment of EVT via DBS. To the authors' knowledge, this is the first time comprehensive intraoperative voice evaluation has been used to guide microelectrode/stimulator placement, as well as the first time that standard pre- and post-DBS assessments have been conducted, demonstrating the efficacy of this tailored DBS approach. PMID:26030706

  15. Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

    ERIC Educational Resources Information Center

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

    2011-01-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…

  16. Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

    ERIC Educational Resources Information Center

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

    2011-01-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using

  17. Obscured clusters. IV. The most massive stars in [DBS2003] 179

    NASA Astrophysics Data System (ADS)

    Borissova, J.; Georgiev, L.; Hanson, M. M.; Clarke, J. R. A.; Kurtev, R.; Ivanov, V. D.; Penaloza, F.; Hillier, D. J.; Zsarg, J.

    2012-10-01

    Aims: We report new results for the massive evolved and main sequence members of the young galactic cluster DBS2003 179. We determine the physical parameters and investigate the high-mass stellar content of the cluster, as well as of its close vicinity. Methods: Our analysis is based on ISAAC/VLT moderate-resolution (R ? 4000) infrared spectroscopy of the brightest cluster members. We derive stellar parameters for sixteen of the stellar members, using full non-local thermodynamic equilibrium modeling of the obtained spectra. Results: The cluster contains three late WN or WR/LBV stars (Obj 4, Obj 15, and Obj 20:MDM 32) and at least five OIf and five OV stars. According to the Hertzsprung-Russell diagram for DBS2003 179, the WR stars show masses above 85 ??, the OIf stars are between 40 and 80 ??, and the main sequence O stars are >20 ??. There are indications of binarity for Obj 4 and Obj 11, and Obj 3 shows a variable spectrum. The cluster is surrounded by a continuous protostar formation region most probably triggered by DBS2003 179. Conclusions: We confirm that DBS2003 179 is young massive cluster (2.5 104 ??) very close to the Galactic center at the distance of 7.9 0.8 kpc. Based on observations gathered with ISAAC,VLT and VISTA of the ESO and the 8.2-m GEMINI telescope within observing programs 81.D-0471, 179.B-2002, and GS-2009A-Q-81.

  18. EFFECT OF MOLECULAR ARCHITECTURE ON DBS-INDUCED BLOCK COPOLYMER GELS: A RHEOLOGICAL STUDY

    EPA Science Inventory

    Dibenzylidene sorbitol (DBS) is capable of gelling a variety of organic solvents and polymeric materials by forming a rigid, 3-D hydrogen-bonded network. In this work, two poly(siloxane)/poly(propylene oxide) segmented copolymers of equal composition and molecular weight, but di...

  19. Flexible retinal electrode array

    DOEpatents

    Okandan, Murat (Albuquerque, NM); Wessendorf, Kurt O. (Albuquerque, NM); Christenson, Todd R. (Albuquerque, NM)

    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.

  20. Micromachined electrode array

    DOEpatents

    Okandan, Murat (Edgewood, NM); Wessendorf, Kurt O. (Albuquerque, NM)