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Sample records for stimulation dbs electrodes

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

    PubMed

    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

  2. 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

  3. 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. PMID:26523416

  4. 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.

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

    PubMed

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

    2016-05-01

    Compared to conventional deep brain stimulation (DBS) for patients with Parkinson's Disease (PD), the newer approach of adaptive DBS (aDBS), regulating stimulation on the basis of the patient's clinical state, promises to achieve better clinical outcomes, avoid adverse-effects and save time for tuning parameters. A remaining challenge before aDBS comes into practical use is to prove its feasibility and its effectiveness in larger groups of patients and in more ecological conditions. We developed an external portable aDBS system prototype designed for clinical testing in freely-moving PD patients with externalized DBS electrodes. From a single-channel bipolar artifact-free recording, it analyses local field potentials (LFPs), during ongoing DBS for tuning stimulation parameters, independent from the specific feedback algorithm implemented. We validated the aDBS system in vitro, by testing both its sensing and closed-loop stimulation capabilities, and then tested it in vivo, focusing on the sensing capabilities. By applying the aDBS system prototype in a patient with PD, we provided evidence that it can track levodopa and DBS-induced LFP spectral power changes among different patient's clinical states. Our system, intended for testing LFP-based feedback strategies for aDBS, should help understanding how and whether aDBS therapy works in PD and indicating future technical and clinical advances. PMID:27029510

  6. Fabrication and initial testing of the μDBS: a novel Deep Brain Stimulation electrode with thousands of individually controllable contacts.

    PubMed

    Willsie, Andrew; Dorval, Alan

    2015-01-01

    High frequency electrical stimulation of deep brain structures such as the subthalamic nucleus in Parkinson's disease or thalamus for essential tremor is used clinically to reduce symptom severity. Deep brain stimulation activates neurons in specific brain structures and connection pathways, overriding aberrant neural activity associated with symptoms. While optimal deep brain stimulation might activate a particular neural structure precisely, existing deep brain stimulation can only generate roughly-spherical regions of activation that do not overlap with any target anatomy. Additionally, side effects linked to stimulation may be the result of limited control over placement of stimulation and its subsequent spread out of optimal target boundaries. We propose a novel lead with thousands of individually controllable contacts capable of asymmetric stimulation profiles. Here we outline the design motivation, manufacturing process, and initial testing of this new electrode design, placing it on track for further directional stimulation studies. PMID:25981752

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

    PubMed Central

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

    2014-01-01

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

  8. 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

  9. 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Zhang, Tianhe C.; Grill, Warren M.

    2010-12-01

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

  12. 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

  13. 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

  14. Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

    PubMed Central

    Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

    2015-01-01

    Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

  15. Choosing electrodes for deep brain stimulation experiments--electrochemical considerations.

    PubMed

    Gimsa, Jan; Habel, Beate; Schreiber, Ute; van Rienen, Ursula; Strauss, Ulf; Gimsa, Ulrike

    2005-03-30

    Deep brain stimulation (DBS) is a therapy of movement disorders including Parkinson's disease (PD). Commercially available electrodes for animal models of Parkinson's disease vary in geometry and material. We characterized such electrodes and found a drift in their properties within minutes and up to about 60 h after immersion in cell culture medium, both with and without a stimulation signal. Electrode properties could largely be restored by proteolytic treatment for platinum/iridium electrodes but not for stainless steel ones. Short-term drift and irreversible aging could be followed by impedance measurements. Aging was accompanied by metal corrosion and erosion of the plastic insulation. For both materials, the degradation rates depended on the current density at the electrode surfaces. Fourier analysis of the DBS pulse (60 micros, repetition rate 130 Hz) revealed harmonic frequencies spanning a band of more than three decades, with significant harmonics up to the MHz range. The band is located in a window imposed by electrode processes and capacitive cell membrane bridging at the low and high frequency ends, respectively. Even though electrode processes are reduced at higher frequencies they only vanish above 1 MHz and cannot be avoided. Therefore, the use of inert electrode materials is of special importance. The neurotoxicity of iron makes avoiding stainless steel electrodes imperative. Future developments need to avoid the use of corrosive materials and current density hot spots at the electrode surface, and to reduce low frequency components in the DBS pulses in order to diminish electrode processes. PMID:15698665

  16. Effect of Deep Brain Stimulation on Parkinson's Nonmotor Symptoms following Unilateral DBS: A Pilot Study

    PubMed Central

    Hwynn, Nelson; Ul Haq, Ihtsham; Malaty, Irene A.; Resnick, Andrew S.; Dai, Yunfeng; Foote, Kelly D.; Fernandez, Hubert H.; Wu, Samuel S.; Oyama, Genko; Jacobson, Charles E.; Kim, Sung K.; Okun, Michael S.

    2011-01-01

    Parkinson's disease (PD) management has traditionally focused largely on motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are effective treatments for motor symptoms. Nonmotor symptoms (NMSs) may also profoundly affect the quality of life. The purpose of this pilot study was to evaluate NMS changes pre- and post-DBS utilizing two recently developed questionnaires. Methods. NMS-Q (questionnaire) and NMS-S (scale) were administered to PD patients before/after unilateral DBS (STN/GPi targets). Results. Ten PD patients (9 STN implants, 1 GPi implant) were included. The three most frequent NMS symptoms identified utilizing NMS-Q in pre-surgical patients were gastrointestinal (100%), sleep (100%), and urinary (90%). NMS sleep subscore significantly decreased (−1.6 points ± 1.8, P = 0.03). The three most frequent NMS symptoms identified in pre-surgical patients using NMS-S were gastrointestinal (90%), mood (80%), and cardiovascular (80%). The largest mean decrease of NMS scores was seen in miscellaneous symptoms (pain, anosmia, weight change, and sweating) (−7 points ± 8.7), and cardiovascular/falls (−1.9, P = 0.02). Conclusion. Non-motor symptoms improved on two separate questionnaires following unilateral DBS for PD. Future studies are needed to confirm these findings and determine their clinical significance as well as to examine the strengths/weaknesses of each questionnaire/scale. PMID:22220288

  17. 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

  18. 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

  19. Prediction of STN-DBS Electrode Implantation Track in Parkinson's Disease by Using Local Field Potentials.

    PubMed

    Telkes, Ilknur; Jimenez-Shahed, Joohi; Viswanathan, Ashwin; Abosch, Aviva; Ince, Nuri F

    2016-01-01

    Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11-32 Hz) and high frequency range (200-450 Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square (RMS) error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11-32 Hz) and the range of high frequency oscillations (200-450 Hz) provided prediction accuracies of 72 and 68% respectively. The best prediction

  20. Prediction of STN-DBS Electrode Implantation Track in Parkinson's Disease by Using Local Field Potentials

    PubMed Central

    Telkes, Ilknur; Jimenez-Shahed, Joohi; Viswanathan, Ashwin; Abosch, Aviva; Ince, Nuri F.

    2016-01-01

    Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11–32 Hz) and high frequency range (200–450 Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square (RMS) error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11–32 Hz) and the range of high frequency oscillations (200–450 Hz) provided prediction accuracies of 72 and 68% respectively. The best

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

    NASA Astrophysics Data System (ADS)

    Butson, Christopher R.; McIntyre, Cameron C.

    2006-03-01

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

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

    PubMed

    Xiao, YiZi; Peña, 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

  3. A Numerical Study to Compare Stimulations by Intraoperative Microelectrodes and Chronic Macroelectrodes in the DBS Technique

    PubMed Central

    Paffi, A.; Apollonio, F.; Puxeddu, M. G.; Parazzini, M.; d'Inzeo, G.; Ravazzani, P.; Liberti, M.

    2013-01-01

    Deep brain stimulation is a clinical technique for the treatment of parkinson's disease based on the electric stimulation, through an implanted electrode, of specific basal ganglia in the brain. To identify the correct target of stimulation and to choose the optimal parameters for the stimulating signal, intraoperative microelectrodes are generally used. However, when they are replaced with the chronic macroelectrode, the effect of the stimulation is often very different. Here, we used numerical simulations to predict the stimulation of neuronal fibers induced by microelectrodes and macroelectrodes placed in different positions with respect to each other. Results indicate that comparable stimulations can be obtained if the chronic macroelectrode is correctly positioned with the same electric center of the intraoperative microelectrode. Otherwise, some groups of fibers may experience a completely different electric stimulation. PMID:24222899

  4. Semi-automatic stereotactic coordinate identification algorithm for routine localization of Deep Brain Stimulation electrodes.

    PubMed

    Hebb, Adam O; Miller, Kai J

    2010-03-15

    Deep Brain Stimulation (DBS) is a routine therapy for movement disorders, and has several emerging indications. We present a novel protocol to define the stereotactic coordinates of metallic DBS implants that may be routinely employed for validating therapeutic anatomical targets. Patients were referred for troubleshooting or new DBS implantation. A volumetric MRI of the brain obtained prior to or during this protocol was formatted to the Anterior Commissure-Posterior Commissure (AC-PC) coordinate system. Patients underwent a CT scan of the brain in an extended Hounsfield unit (EHU) mode. A semi-automatic detection algorithm based on a Normalized Mutual Information (NMI) co-registration method was implemented to measure the AC-PC coordinates of each DBS contact. This algorithm was validated using manual DBS contact identification. Fifty MRI-CT image pairs were available in 39 patients with a total of 336 DBS electrodes. The median and mean Euclidean distance errors for automatic identification of electrode locations were 0.20mm and 0.22 mm, respectively. This method is an accurate method of localization of active DBS contacts within the sub-cortical region. As the investigational indications of DBS expand, this method may be used for verification of final implant coordinates, critical for understanding clinical benefit and comparing efficacy between subjects. PMID:20036691

  5. 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 MΩ 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

  6. 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.

  7. Electrode array for neural stimulation

    DOEpatents

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

    2011-08-16

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

  8. Neural stimulation and recording electrodes.

    PubMed

    Cogan, Stuart F

    2008-01-01

    Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes. PMID:18429704

  9. 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.

  10. 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.

  11. Localization of deep brain stimulation electrodes via metal artifacts in CT images.

    PubMed

    Motevakel, Amir; Medvedev, Alexander

    2014-01-01

    In Deep Brain Stimulation (DBS), the location of implanted electrodes in the brain has direct influence on the therapeutic effect of the treatment. This work deals with estimating the position of the implanted DBS electrodes from the images registered by X-ray Computed Tomography (CT) scanners. A technique named junction method that takes advantage of the streak artifacts created by the metal parts of the electrodes in CT images is proposed for this purpose. To start with, the brain image is extracted by defining a brain mask. Next, the edges are intensified by applying a Gaussian convolution operator followed by a measure of the second derivative of the image along all directions in the image plane. Criteria of adjacency and length are applied to the lines detected by the Hough transform to distinguish between tracks of streak artifacts and the brain structure. At some points, straight lines are distorted by noise. To handle this issue, all lines that fit same line equation are merged. The horizontal line connecting the two DBS electrodes (one in each cerebral hemisphere) is called electrode line. To specify the electrodes position, intersections of the electrode line with every other line are marked. Finally, to obtain the vertical position estimate, the above algorithm is applied to the image stack. PMID:25570143

  12. 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

  13. Graphene electrodes for stimulation of neuronal cells

    NASA Astrophysics Data System (ADS)

    Koerbitzer, Berit; Krauss, Peter; Nick, Christoph; Yadav, Sandeep; Schneider, Joerg J.; Thielemann, Christiane

    2016-06-01

    Graphene has the ability to improve the electrical interface between neuronal cells and electrodes used for recording and stimulation purposes. It provides a biocompatible coating for common electrode materials such as gold and improves the electrode properties. Graphene electrodes are also prepared on SiO2 substrate to benefit from its optical properties like transparency. We perform electrochemical and Raman characterization of gold electrodes with graphene coating and compare them with graphene on SiO2 substrate. It was found that the substrate plays an important role in the performance of graphene and show that graphene on SiO2 substrate is a very promising material combination for stimulation electrodes.

  14. DBS for Obesity.

    PubMed

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

    2016-01-01

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

  15. Modeling the current distribution across the depth electrode-brain interface in deep brain stimulation.

    PubMed

    Yousif, Nada; Liu, Xuguang

    2007-09-01

    The mismatch between the extensive clinical use of deep brain stimulation (DBS), which is being used to treat an increasing number of neurological disorders, and the lack of understanding of the underlying mechanisms is confounded by the difficulty of measuring the spread of electric current in the brain in vivo. In this article we present a brief review of the recent computational models that simulate the electric current and field distribution in 3D space and, consequently, make estimations of the brain volume being modulated by therapeutic DBS. Such structural modeling work can be categorized into three main approaches: target-specific modeling, models of instrumentation and modeling the electrode-brain interface. Comments are made for each of these approaches with emphasis on our electrode-brain interface modeling, since the stimulating current must travel across the electrode-brain interface in order to reach the surrounding brain tissue and modulate the pathological neural activity. For future modeling work, a combined approach needs to be taken to reveal the underlying mechanisms, and both structural and dynamic models need to be clinically validated to make reliable predictions about the therapeutic effect of DBS in order to assist clinical practice. PMID:17850197

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  17. 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

  18. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. Bilateral adaptive deep brain stimulation is effective in Parkinson's disease

    PubMed Central

    Little, Simon; Beudel, Martijn; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Hariz, Marwan; Neal, Spencer; Cheeran, Binith; Cagnan, Hayriye; Gratwicke, James; Aziz, Tipu Z; Pogosyan, Alex; Brown, Peter

    2016-01-01

    Introduction & objectives Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson’s disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication. Methods We applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features. Results UPDRS scores were 43% (p=0.04; Cohen’s d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS. Conclusion Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states. PMID:26424898

  3. Anatomo-clinical atlases correlate clinical data and electrode contact coordinates: application to subthalamic deep brain stimulation.

    PubMed

    Lalys, Florent; Haegelen, Claire; Mehri, Maroua; Drapier, Sophie; Vérin, Marc; Jannin, Pierre

    2013-01-30

    For patients suffering from Parkinson's disease with severe movement disorders, functional surgery may be required when medical therapy is not effective. In Deep Brain Stimulation (DBS), electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). The quality of patient surgical outcome is generally related to the accuracy of nucleus targeting during surgery. In this paper, we focused on identifying optimum sites for STN DBS by studying symptomatic motor improvement along with neuropsychological side effects. We described successive steps for constructing digital atlases gathering patient's location of electrode contacts automatically segmented from postoperative images, and clinical scores. Three motor and five neuropsychological scores were included in the study. Correlations with active contact locations were carried out using an adapted hierarchical ascendant classification. Such analysis enabled the extraction of representative clusters to determine the optimum site for therapeutic STN DBS. For each clinical score, we built an anatomo-clinical atlas representing its improvement or deterioration in relation with the anatomical location of electrodes and from a population of implanted patients. To the best of our knowledge, we reported for the first time a discrepancy between a very good motor improvement by targeting the postero-superior region of the STN and an inevitable deterioration of the categorical and phonemic fluency in the same region. Such atlases and associated analysis may help better understanding of functional mapping in deep structures and may help pre-operative decision-making process and especially targeting. PMID:23147008

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

    PubMed Central

    Paffi, Alessandra; Camera, Francesca; Apollonio, Francesca; d’Inzeo, 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

  5. 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

  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. 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

  8. 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

  9. STN-DBS Reduces Saccadic Hypometria but Not Visuospatial Bias in Parkinson's Disease Patients.

    PubMed

    Fischer, Petra; Ossandón, José P; Keyser, Johannes; Gulberti, Alessandro; Wilming, Niklas; Hamel, Wolfgang; Köppen, Johannes; Buhmann, Carsten; Westphal, Manfred; Gerloff, Christian; Moll, Christian K E; Engel, Andreas K; König, Peter

    2016-01-01

    In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson's disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye-tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age-matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments "but not higher-level exploration patterns" are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits. PMID:27199693

  10. STN-DBS Reduces Saccadic Hypometria but Not Visuospatial Bias in Parkinson's Disease Patients

    PubMed Central

    Fischer, Petra; Ossandón, José P.; Keyser, Johannes; Gulberti, Alessandro; Wilming, Niklas; Hamel, Wolfgang; Köppen, Johannes; Buhmann, Carsten; Westphal, Manfred; Gerloff, Christian; Moll, Christian K. E.; Engel, Andreas K.; König, Peter

    2016-01-01

    In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson's disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye-tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age-matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments “but not higher-level exploration patterns” are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits. PMID:27199693

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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 Parkinson’s 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

  14. 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

  15. Differential effects of deep brain stimulation on verbal fluency.

    PubMed

    Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

    2014-07-01

    We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. PMID:24815947

  16. 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

  17. 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

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

    PubMed

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

    2011-01-01

    Neurophysiological and computer modelling studies have shown that electrode montage is a critical parameter to determine the neuromodulatory effects of transcranial direct current stimulation (tDCS). We tested these results clinically by systematically investigating optimal tDCS electrode montage in stroke. Ten patients received in a counterbalanced and randomised order the following conditions of stimulation (i) anodal stimulation of affected M1 (primary motor cortex) and cathodal stimulation of unaffected M1 ('bilateral tDCS'); (ii) anodal stimulation of affected M1 and cathodal stimulation of contralateral supraorbital area ('anodal tDCS'); (iii) cathodal stimulation of unaffected M1 and anodal stimulation of contralateral supraorbital area ('cathodal tDCS'); (iv) anodal stimulation of affected M1 and cathodal stimulation of contralateral deltoid muscle ('extra-cephalic tDCS') and (v) sham stimulation. We used the Jebsen-Taylor Test (JTT) as a widely accepted measure of upper limb function. Bilateral tDCS, anodal tDCS and cathodal tDCS were shown to be associated with significant improvements on the JTT. Placing the reference electrode in an extracephalic position and use of sham stimulation did not induce any significant effects. This small sham controlled cross-over clinical trial is important to provide additional data on the clinical effects of tDCS in stroke and for planning and designing future large tDCS trials in patients with stroke. PMID:21110732

  19. 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.

  20. Reduction in DBS frequency improves balance difficulties after thalamic DBS for essential tremor.

    PubMed

    Ramirez-Zamora, Adolfo; Boggs, Hans; Pilitsis, Julie G

    2016-08-15

    Essential tremor (ET) is a syndrome characterized by the presence of symmetric, moderate to high frequency postural and action tremors of the limbs. Additionally, increasing evidence indicates the occurrence of associated cerebellar features in ET patients including impaired gait and balance. Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been shown to be an effective treatment for medically-refractory ET tremor but its effects on balance remain unclear with conflicting results reported. In this article, we report the effects of frequency modification in four patients with disequilibrium after DBS and review available literature regarding the effects of neurostimulation on balance in ET. Reduction in DBS frequency (10-20Hz reduction intervals) to the lowest effective settings for tremor control was conducted followed by immediate and 4-week assessment of disequilibrium. All patients reported improvement in balance ranging from mild to marked benefit on clinical global impression scale and in the posture and gait disturbance sub-scores of the International Cooperative Ataxia Rating Scale (ICARS). There was no significant difference in tremor control with DBS frequency adjustments. Our results suggest a relationship between the effects of high-frequency stimulation and disequilibrium in ET patients treated with bilateral or unilateral DBS. Additional larger, prospective studies are warranted to validate these results and discern the relationship between DBS stimulation settings and cerebellar findings in ET. PMID:27423573

  1. 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.

  2. Critical reappraisal of DBS targeting for movement disorders.

    PubMed

    Guzzi, Giusy; Della Torre, Attilio; Chirchiglia, Domenico; Volpentesta, Giorgio; Lavano, Angelo

    2016-06-01

    Deep brain stimulation (DBS) is used as a surgical treatment of movement disorders such as Parkinson's disease, dystonia and essential tremor. Fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. In 2002 DBS of the subthalamic nucleus (STN) and the globus pallidus internus (GPi) was approved for use in patients with PD. Next year, DBS of Gpi and STN for dystonia received a Humanitarian Device exemption from the FDA. The commonly targets for DBS are subthalamic nucleus (STN) or globus pallidus internus (GPi) for Parkinson's disease, Gpi for dystonia and ventro-intermediate (VIM) nucleus of the thalamus for essential tremor. However, VIM DBS cannot sufficiently improve akinesia and rigidity. Pedunculopontine nucleus (PPN) is currently investigated as potential target to improve gait and posture. It is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of patients. In this article we review the present state of DBS for movement disorders, appropriate indications, practical effects and stimulation-induced adverse events established in previous studies. We discuss target selection and the effect of DBS on motor and non-motor symptoms of Parkinson's disease, dystonia and essential tremor. PMID:27015393

  3. Deep brain stimulation and development of a high-grade glioma: incidental or causal association?

    PubMed

    Mindermann, Thomas; Mendelowitsch, Aminadav

    2016-05-01

    We report the case of a patient in whom 8.8 years following the implantation of a bilateral deep brain stimulation (DBS) into the Vim, a high-grade glioma was diagnosed in close proximity to the two electrode leads. A possible relationship between the permanent DBS and the development of the brain tumour is discussed. PMID:26993141

  4. Nucleus accumbens stimulation in pathological obesity.

    PubMed

    Harat, Marek; Rudaś, Marcin; Zieliński, Piotr; Birska, Julita; Sokal, Paweł

    2016-01-01

    One of the potential treatment methods of obesity is deep brain stimulation (DBS) of nucleus accumbens. We describe the case of 19 years old woman with hypothalamic obesity. She weighted 151.4 kg before DBS and the non-surgical methods proved to be inefficient. She was treated with implantation of DBS electrode to nucleus accumbens bilaterally. Results were measured with body mass index and neuropsychological tests. Follow-up was 14 months. Fourteen months after surgery weight was 138 kg, BMI was 48.3. Neuropsychological test results were intact. The presented case supports the thesis of treatment of obesity with nucleus accumbens stimulation. PMID:27154450

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

    PubMed Central

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

    2013-01-01

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

  6. Matching geometry and stimulation parameters of electrodes for deep brain stimulation experiments--numerical considerations.

    PubMed

    Gimsa, Ulrike; Schreiber, Ute; Habel, Beate; Flehr, Jürgen; 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

  7. Diffusion-bonded electrodes for chronic neural stimulation.

    PubMed

    Shah, Kedar G; Lee, Kye Young; Tolosa, Vanessa; Tooker, Angela; Felix, Sarah; Pannu, Satinderpall

    2014-01-01

    We report a novel method to fabricate chronic neural interfaces with the intent to combine the reliability and lifetime of bulk metal electrodes, with the miniaturization and mechanical flexibility of thin-film polymer microelectrode arrays. 10 μm thick platinum discs were laser cut from a foil into the shape of individual electrodes, and coated with gold on the backside. The discs were bonded to a microelectrode array with gold bond pads via gold-gold inter-diffusion using a flipchip bonder. Electrode bonding and adhesion was characterized using mechanical shear testing and electrical testing. Electrode performance was characterized in vitro using electrochemical impedance spectroscopy and cyclic voltammetry. Biphasic electrical pulsing experiments were conducted on the bonded electrodes to study degradation of the electrode; the preliminary results show that the electrodes can withstand at least 4,900 million pulses with no adverse electrochemical or visual degradation. Overall, this is a promising new method for fabricating chronic neural electrodes for stimulation or recording that combines the reliability of commercial bulk electrodes with the miniaturization and versatility of microfabricated technologies. PMID:25569992

  8. Diaphragmatic activity induced by cortical stimulation: surface versus esophageal electrodes.

    PubMed

    Gea, J; Espadaler, J M; Guiu, R; Aran, X; Seoane, L; Broquetas, J M

    1993-02-01

    Evoked responses of the diaphragm can be induced by magnetic cortical stimulation and recorded by either surface or esophageal electrodes. The former recording system is tolerated better by the patient but has potential problems with the specificity of the diaphragmatic signal. This study compares the responses of the diaphragm to cortical stimulation that were recorded simultaneously with surface and esophageal electrodes on seven patients (61 +/- 4 yr) with chronic obstructive pulmonary diseases. Stimuli were delivered in three ventilatory conditions: at baseline, during deep breathing, and during voluntary panting. No differences were observed between results recorded by surface and esophageal electrodes [amplitude of the compound motor of the action potential (CMAP), 0.8 +/- 0.1 vs. 0.8 +/- 0.1 mV, NS; latency, 13.1 +/- 0.4 vs. 12.6 +/- 0.5 ms, NS]. In addition, significant correlations were found (CMAP, r = 0.77, P < 0.001; latency, r = 0.71, P = 0.002). The concordance analysis, however, indicated some dissimilarity between the recordings of the electrodes (CMAP, R1 = 0.31; latency, R1 = 0.26). These differences may be due to the area of the muscle mainly recorded by each electrode and/or to the additional activity from other muscles recorded by surface electrodes. On the other hand, the diaphragmatic responses observed in these patients with chronic obstructive pulmonary diseases were similar to those previously reported in healthy subjects. PMID:8458780

  9. Pallidal stimulation suppresses pathological dysrhythmia in the parkinsonian motor cortex

    PubMed Central

    Turner, Robert S.

    2015-01-01

    Although there is general consensus that deep brain stimulation (DBS) yields substantial clinical benefit in patients with Parkinson's disease (PD), the therapeutic mechanism of DBS remains a matter of debate. Recent studies demonstrate that DBS targeting the globus pallidus internus (GPi-DBS) suppresses pathological oscillations in firing rate and between-cell spike synchrony in the vicinity of the electrode but has negligible effects on population-level firing rate or the prevalence of burst firing. The present investigation examines the downstream consequences of GPi-DBS at the level of the primary motor cortex (M1). Multielectrode, single cell recordings were conducted in the M1 of two parkinsonian nonhuman primates (Macaca fasicularis). GPi-DBS that induced significant reductions in muscular rigidity also reduced the prevalence of both beta (12–30 Hz) oscillations in single unit firing rates and of coherent spiking between pairs of M1 neurons. In individual neurons, GPi-DBS-induced increases in mean firing rate were three times more common than decreases; however, averaged across the population of M1 neurons, GPi-DBS induced no net change in mean firing rate. The population-level prevalence of burst firing was also not affected by GPi-DBS. The results are consistent with the hypothesis that suppression of both pathological, beta oscillations and synchronous activity throughout the cortico-basal ganglia network is a major therapeutic mechanism of GPi-DBS. PMID:25652922

  10. Perceptual interactions between electrodes using focused and monopolar cochlear stimulation.

    PubMed

    Marozeau, Jeremy; McDermott, Hugh J; Swanson, Brett A; McKay, Colette M

    2015-06-01

    In today's cochlear implant (CI) systems, the monopolar (MP) electrode configuration is the most commonly used stimulation mode, requiring only a single current source. However, with an implant that will allow simultaneous activation of multiple independent current sources, it is possible to implement an all-polar (AP) stimulation mode designed to create a focused electrical field. The goal of this experiment was to study the potential benefits of this all-polar mode for reducing uncontrolled electrode interactions compared with the monopolar mode. The five participants who took part in the study were implanted with a research device that was connected via a percutaneous connector to a benchtop stimulator providing 22 independent current sources. The perceptual effects of the AP mode were tested in three experiments. In Experiment 1, the current level difference between loudness-matched sequential and simultaneous stimuli composed of 2 spatially separated pulse trains was measured as function of the electrode separation. Results indicated a strong current-summation interaction for simultaneous stimuli in the MP mode for separations up to at least 4.8 mm. No significant interaction was found in the AP mode beyond a separation of 2.4 mm. In Experiment 2, a forward-masking paradigm was used with fixed equally loud probes in AP and MP modes, and AP maskers presented on different electrode positions. Results indicated a similar spatial masking pattern between modes. In Experiment 3, subjects were asked to discriminate between across-electrode temporal delays. It was hypothesized that discrimination would decrease with electrode separation faster in AP compared to MP modes. However, results showed no difference between the two modes. Overall, the results indicated that the AP mode produced less current spread than MP mode but did not lead to a significant advantage in terms of spread of neuronal excitation at equally loud levels. PMID:25742726

  11. Electrode positioning and montage in transcranial direct current stimulation.

    PubMed

    DaSilva, Alexandre F; Volz, Magdalena Sarah; Bikson, Marom; Fregni, Felipe

    2011-01-01

    Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders--especially when applied over several consecutive sessions. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation. PMID:21654618

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

    PubMed

    Pečlin, Polona; Mehle, Andraž; Karpe, Blaž; 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

  13. 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.

  14. 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

  15. 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

  16. Preparation of etched tantalum semimicro capacitor stimulation electrodes.

    PubMed

    Robblee, L S; Kelliher, E M; Langmuir, M E; Vartanian, H; McHardy, J

    1983-03-01

    The ideal electrode for stimulation of the nervous system is one that will inject charge by purely capacitive processes. One approach is to exploit the type of metal-oxide combination used in electrolytic capacitors, e.g., Ta/Ta2O5. For this purpose, fine tantalum wire (0.25 mm diam) was etched electrolytically at constant current in a methanol solution of NH4Br containing 1.5 wt % H2O. Electrolytic etching produced a conical tip with a length of ca. 0.5 mm and shaft diameters ranging from 0.10 to 0.16 mm. The etched electrodes were anodized to 10 V (vs. SCE) in 0.1 vol % H3PO4. The capacitance values normalized to geometric area of etched electrodes ranged from 0.13 to 0.33 micro F mm-2. Comparison of these values to the capacitance of "smooth" tantalum anodized to 10 V (0.011 micro F mm-2) indicated that the degree of surface enhancement, or etch ratio, was 12-30. The surface roughness was confirmed by scanning electron microscopy studies which revealed an intricate array of irregularly shaped surface projections about 1-2 micrometers wide. The etched electrodes were capable of delivering 0.06-0.1 micro C of charge with 0.1 ms pulses at a pulse repetition rate of 400 Hz when operated at 50% of the anodization voltage. This quantity of charge corresponded to volumetric charge densities of 20-30 micro C mm-3 and area charge densities of 0.55-0.88 micro C mm-2. Charge storage was proportionately higher at higher fractional values of the formation voltage. Leakage currents at 5 V were ca. 2 nA. Neither long-term passive storage (1500 h) nor extended pulsing time (18 h) had a deleterious effect on electrode performance. The trend in electrical stimulation work is toward smaller electrodes. The procedures developed in this study should be particularly well-suited to the fabrication of even smaller electrodes because of the favorable electrical and geometric characteristics of the etched surface. PMID:6841372

  17. Analysis of High-Perimeter Planar Electrodes for Efficient Neural Stimulation

    PubMed Central

    Wei, Xuefeng F.; Grill, Warren M.

    2009-01-01

    Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to two, three or four times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input–output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries. PMID:19936312

  18. DBS in Tourette syndrome: where are we standing now?

    PubMed

    Andrade, Pablo; Visser-Vandewalle, Veerle

    2016-07-01

    Deep brain stimulation (DBS) has emerged as an established effective and safe treatment option for a small subset of patients with severe Tourette syndrome (TS) refractory to psychological and pharmacological treatments. Several targets have been implicated in the study of the effects of DBS on TS symptomatology. The targets applied for DBS in TS include the thalamus, the globus pallidus internus, the internal capsule/nucleus accumbens, the globus pallidus externus and the subthalamic nucleus. In the majority of studies there has been a significant clinical benefit on tics. Nevertheless, the best target has not been defined yet. Up until now, only five double blind randomized controlled trials have been carried out worldwide for a total of 32 patients. Thus, the new recommendations for DBS in TS emphasize the importance of standardized recordings of all pre-, intra-, and postoperative data to optimize the registration of patients so that results can be compared. Recent reports have shown that standard continuous DBS for TS patients may not be the most optimal paradigms to pursue. Adaptive stimulation and the use of human-computer interfaces might in the future optimize the results of DBS in TS because of the paroxysmal nature of the disease. PMID:27209036

  19. Dopamine Release in the Nonhuman Primate Caudate and Putamen Depends upon Site of Stimulation in the Subthalamic Nucleus

    PubMed Central

    Min, Hoon-Ki; Ross, Erika K.; Jo, Hang Joon; Cho, Shinho; Settell, Megan L.; Jeong, Ju Ho; Duffy, Penelope S.; Chang, Su-Youne; Bennet, Kevin E.; Blaha, Charles D.

    2016-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson's disease. Although DBS has recognized clinical utility, its biologic mechanisms are not fully understood, and whether dopamine release is a potential factor in those mechanisms is in dispute. We tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and the site of recording in the caudate and putamen. We conducted DBS with miniature, scaled-to-animal size, multicontact electrodes and used functional magnetic resonance imaging to identify the best dopamine recording site in the brains of nonhuman primates (rhesus macaques), which are highly representative of human brain anatomy and circuitry. Real-time stimulation-evoked dopamine release was monitored using in vivo fast-scan cyclic voltammetry. This study demonstrates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site. SIGNIFICANCE STATEMENT Electrical stimulation of deep structures of the brain, or deep brain stimulation (DBS), is used to modulate pathological brain activity. However, technological limitations and incomplete understanding of the therapeutic mechanisms of DBS prevent personalization of this therapy and may contribute to less-than-optimal outcomes. We have demonstrated that DBS coincides with changes in dopamine neurotransmitter release in the basal ganglia. Here we mapped relationships between DBS and changes in neurochemical activity. Importantly, this study shows that DBS-evoked dopamine release can be reduced or increased by refocusing the DBS on a slightly different stimulation site. PMID:27251623

  20. Deep brain stimulation for Parkinson's disease using frameless technology.

    PubMed

    Cheng, Chun-Yuan; Hsing, Ming-Tai; Chen, Yung-Hsiang; Wu, Sey-Lin; Sy, Hiu Ngar; Chen, Chien-Min; Yang, Yu-Jen; Lee, Meng-Chih

    2014-06-01

    Historically deep brain stimulation (DBS) for Parkinson's disease (PD) has been performed by frame-based stereotaxy. However, recently the option of frameless stereotaxy has become available. This avoids the potential discomfort the patient may experience because of the frame fixed to the head. This study compared clinical outcomes of DBS performed using frame-based and frameless procedures for PD patients. Twelve patients underwent DBS operations; from these patients, six underwent frame-based and six underwent frameless DBS operations, and assessed 6 months later. Operation time, subthalamic electrode contact length, microelectrode recording (MER) tracts, and unified PD rating scale scores were evaluated and the scores were compared. This small study found no differences between frameless or frame based DBS, and concludes that framless system maybe an acceptable alternative. PMID:24138684

  1. 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.

  2. Optimal Geometry and Stimulating Mechanism of Deep-brain Electrode—Role of Electrode Contact Geometry

    NASA Astrophysics Data System (ADS)

    Lian, Qin; Wang, Jue; Liu, Hongzhong; Li, DiChen

    2008-09-01

    Deep brain stimulation has been demonstrated as an effective treatment for various locomotion disorders; however, the stimulating mechanism by which these high frequency electrical pulses intertwined with the geometry of electrode act on neuronal activity is unclear. Finite element analytic model of electrode in deep brain stimulation was established in this paper to investigate the impact of changes of electrode contact geometry on the cerebral electric field. The computational calculation showed that electrode contact configuration not only determined the stimulation position of electrode in the deep brain, but also played an important role on stimulated tissue area and stimulated field strength, which can provide more practical design rule for the electrode in deep brain stimulation.

  3. Anaesthetic management of shoulder arthroscopic repair in Parkinson's disease with deep brain stimulator

    PubMed Central

    Gandhi, Ranju; Chawla, Reeta

    2014-01-01

    We describe the anaesthetic management of arthroscopic repair for complete rotator cuff tear of shoulder in a 59-year-old female with Parkinson's disease (PD) with deep brain stimulator (DBS) using a combination of general anaesthesia with interscalene approach to brachial plexus block. The DBS consists of implanted electrodes in the brain connected to the implantable pulse generator (IPG) normally placed in the anterior chest wall subcutaneously. It can be programmed externally from a hand-held device placed directly over the battery stimulator unit. In our patient, IPG with its leads was located in close vicinity of the operative site with potential for DBS malfunction. Implications of DBS in a patient with PD for shoulder arthroscopy for anaesthesiologist are discussed along with a brief review of DBS. PMID:25024475

  4. Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

    PubMed

    Stefurak, Taresa; Mikulis, David; Mayberg, Helen; Lang, Anthony E; Hevenor, Stephanie; Pahapill, Peter; Saint-Cyr, Jean; Lozano, Andres

    2003-12-01

    Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity

  5. Laparoscopic insertion of gastric electrodes for electrical stimulation.

    PubMed

    Brody, Fred; Nam, Arthur; Drenon, Elizabeth; Ali, Aamir; Soffer, Edy

    2007-02-01

    Gastric electrical stimulation can provide symptomatic relief for patients with refractory gastroparesis. Traditionally, these wires are placed through a midline laparotomy. This paper describes and illustrates, in detail, the laparoscopic technique for successful implantation. Thirty-one consecutive patients from October 2003 to March 2005 underwent laparoscopic insertion of gastric stimulating wires for gastroparesis. Twenty-six patients were female. Four laparoscopic ports were used to insert a pair of electrodes. Anterior, cephalad retraction of the gastric wall is critical for accurate seromuscular placement of gastric leads. Intraoperative endoscopy was used to verify the seromuscular placement of the leads. Both leads were secured to a subcutaneous generator and electrical parameters were immediately established in the operating room. Patient demographics, operative details, and postoperative morbidities were recorded. All procedures were completed laparoscopically. The mean operative time was 114.4 +/- 20.9 minutes (range, 95-140). No perioperative mortality occurred. Two patients developed cellulitis at the generator site postoperatively and oral antibiotics were prescribed for one week postoperatively. No hardware was removed. Two patients had their generators repositioned due to pain at the pocket site. Gastric electrical stimulation is a novel treatment modality for patients with refractory gastroparesis and can be accomplished safely via laparoscopy. Laparoscopic insertion is successful even in patients with prior surgery and intact gastrointestinal tubes. Long-term follow-up and the current prospective multicenter trial continue to assess the efficacy of this treatment modality. PMID:17362169

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Evaluation of direct bladder stimulation with stainless steel woven eye electrodes.

    PubMed

    Walter, J S; Wheeler, J S; Cogan, S F; Plishka, M; Riedy, L W; Wurster, R D

    1993-12-01

    Encouraged by recent clinical reports of micturition induced in patients by direct bladder stimulation, we conducted a study of optimum methods of direct bladder stimulation. During surgery six male cats received eight large surface-area woven eye electrodes sutured to the bladder wall serosa, four on the bladder dome and four adjacent to the trigone area. Two additional small surface-area single knot electrodes were sutured in the trigone area. Suprapubic and intraperitoneal tubes were placed for pressure recording and bladder filling. Leg and pelvic floor EMG electrodes were also used for tethered recordings. One to eight weeks after surgery, optimum stimulation methods were evaluated as the animal freely moved about a urodynamic recording cage. Electrodes in the trigone region were more effective than electrodes on the dome and induced bladder contractions and voiding similar to spontaneously induced voiding with bladder filing. Large surface area, woven eye electrodes, composed of multistranded 316LVM stainless steel wire, were more effective than smaller surface area single knot electrodes. High stimulating frequencies (40 Hz) were better than lower frequencies (10 to 20 Hz), and a 1 millisecond pulse duration was optimal. Pulsing with stimulating currents from 10 to 25 mA induced effective bladder contractions with voiding when applied for 3 seconds. However, lower currents using longer stimulation periods were also effective. Bipolar electrodes with both electrodes on the bladder wall were superior to monopolar arrangements with the positive ground electrode along the animal's back. We concluded that in the able-bodied cat model, bladder contractile activity for micturition can be induced with direct bladder stimulation and with little discomfort. An effective stimulation protocol consists of capacitor-coupled monophasic pulses with large surface area bipolar electrodes in the trigone region. Stimulating parameters of 40 Hz, 1 msec., 10 to 25 mA applied for

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

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

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

  16. Spatiotemporal visualization of deep brain stimulation-induced effects in the subthalamic nucleus.

    PubMed

    Yousif, Nada; Borisyuk, Roman; Pavese, Nicola; Nandi, Dipankar; Bain, Peter

    2012-07-01

    Deep brain stimulation (DBS) is a successful surgical therapy used to treat the disabling symptoms of movement disorders such as Parkinson's disease. It involves the chronic stimulation of disorder-specific nuclei. However, the mechanisms that lead to clinical improvements remain unclear. Consequently, this slows the optimization of present-day DBS therapy and hinders its future development and application. We used a computational model to calculate the distribution of electric potential induced by DBS and study the effect of stimulation on the spiking activity of a subthalamic nucleus (STN) projection neuron. We previously showed that such a model can reveal detailed spatial effects of stimulation in the vicinity of the electrode. However, this multi-compartmental STN neuron model can fire in either a burst or tonic mode and, in this study, we hypothesized that the firing mode of the cell will have a major impact on the DBS-induced effects. Our simulations showed that the bursting model exhibits behaviour observed in studies of high-frequency stimulation of STN neurons, such as the presence of a silent period at stimulation offset and frequency-dependent stimulation effects. We validated the model by simulating the clinical parameter settings used for a Parkinsonian patient and showed, in a patient-specific anatomical model, that the region of affected tissue is consistent with clinical observations of the optimal DBS site. Our results demonstrated a method of quantitatively assessing neuronal changes induced by DBS, to maximize therapeutic benefit and minimize unwanted side effects. PMID:22805069

  17. A simulation study: effect of the inter-electrode distance, electrode size and shape in transcutaneous electrical stimulation.

    PubMed

    Gomez-Tames, Jose D; Gonzalez, Jose; Yu, Wenwei

    2012-01-01

    Transcutaneous Electrical Stimulation (TES) has been used widely to recover motor functions in neurologically impaired individuals by artificially activating skeletal muscles using superficial electrodes. Some simulation studies have investigated the percentage of fibers activated in denervated skeletal muscles, the comfort and selectivity, and the influence of fat thickness in the case of obese people, to optimize the inter-electrode distance and electrode size. However, the effect of the inter-electrode distance, electrode shape and electrode size might be further analyzed using the selectivity, activation depth and activation volume. In this regard, we developed a 3D multi-layer (skin, fat, muscle, and nerve) thigh model coupled with a mammalian nerve model using a finite element method for optimization of TES therapy. Different evaluation indices (motor threshold, activation depth, selectivity and activation volume) were inspected to compare different TES parameters in terms of nerve activation. The simulation results agreed with experimental data and new insights were obtained: selectivity is better in small electrodes; nevertheless, in high current stimulation, small electrodes and large electrodes have similar selectivity. PMID:23366700

  18. Deep brain stimulation: new techniques.

    PubMed

    Hariz, Marwan

    2014-01-01

    The technology of the hardware used in deep brain stimulation (DBS), and the mode of delivering the stimulation have not significantly evolved since the start of the modern era of DBS 25 years ago. However, new technology is now being developed along several avenues. New features of the implantable pulse generator (IPG) allow fractionation of the electric current into variable proportions between different contacts of the multi-polar lead. Another design consists in leads that allow selective current steering from directionally placed electrode contacts that would deliver the stimulation in a specific direction or even create a directional shaped electric field that would conform to the anatomy of the brain target aimed at, avoiding adjacent structures, and thus avoiding side effects. Closed loop adaptive stimulation technologies are being developed, allowing a tracking of the pathological local field potential of the brain target, and delivering automatically the stimulation to suppress the pathological activity as soon as it is detected and for as long as needed. This feature may contribute to a DBS therapy "on demand", instead of continuously. Finally, advances in imaging technology are providing "new" brain targets, and increasingly allowing DBS to be performed accurately while avoiding the risks of microelectrode recording. PMID:24262179

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

    PubMed

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

    2011-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  2. Effects of STN DBS on Memory Guided Force Control in Parkinson’s 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 Parkinson’s 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

  3. Effects of STN DBS on memory guided force control in Parkinson's disease (June 2007).

    PubMed

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

    2007-06-01

    This study examined the control of elbow force in nine patients with Parkinson's 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

  4. Investigating the interfacial properties of electrochemically roughened platinum electrodes for neural stimulation.

    PubMed

    Weremfo, Alexander; Carter, Paul; Hibbert, D Brynn; Zhao, Chuan

    2015-03-01

    Platinum electrodes have been electrochemically roughened (roughness factors up to 430) and evaluated for use as neural stimulation electrodes. The roughened electrodes show superior interfacial properties with increasing surface roughness. The roughened electrode (fR = 250) has a charge injection limit of 1.0 mC cm(-2) (400 μs pulse width), which is superior to that of titanium nitride (0.87 mC cm(-2)) but comparable to that of carbon nanotubes (1.0-1.6 mC cm(-2)). The surface roughness can also be optimized for different neural stimulation applications based on the available charge density at a particular pulse width of stimulation. The roughened platinum electrodes demonstrated good mechanical stability under harsh ultrasonication and electrochemical stability under continuous biphasic stimulation, indicating the potential of this biological interface to be safe and stable. PMID:25669232

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  6. DBS platforms - A viable solution

    NASA Astrophysics Data System (ADS)

    Cohen, N. L.; Stone, G. R.

    1982-12-01

    Various design options for the basic direct broadcast satellite (DBS) system are discussed. The first generation spacecraft are constrained by time zone problems, noting that one unit is insufficient to provide direct TV to an entire continent. An 800 W traveling wave amplifier is sufficient for full coverage of the entire U.S., while 200 W amplifiers are capable of single channel broadcast to a quarter to a third of the U.S. land area. A total of 24-32 satellites costing a total of $3.2-4.8 billion is required to provide full U.S. coverage with first generation DBS systems. The Shuttle is described as the means to providing GEO DBS services at affordable costs. Four large platforms, weighing 5300 kg, could be placed in GEO by a Centaur transfer stage after launch into LEO on the Shuttle. Studies have shown that four platforms, each with a 40 channel capability, power generating capacity of 30 kW, and 100% eclipse capability, could provide coverage for the entire U.S. Beam-shaping techniques offer any desired illumination pattern. Details of the institutional barriers which must be satisfied before the $500 million spacecraft could be launched are outlined.

  7. [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

  8. Construction of a Simple Suction Electrode for Extracellular Recording and Stimulation

    PubMed Central

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

    2007-01-01

    Principles of signal transmission in nervous systems are commonly demonstrated in the undergraduate neuroscience laboratory through extracellular recording of nerve and muscle action potentials. Here we describe the construction of a simple suction electrode that we use routinely in our laboratory classes for nerve recording and stimulation. The electrode parts are relatively inexpensive, easily available from established scientific and electronic distributors and local hardware stores, and the electrode is resilient to student handling. Our undergraduate students use this electrode design for high resolution, extracellular recordings of action potentials from crayfish motor and sensory nerves and insect muscle, and for stimulation of crustacean and insect motor nerves. PMID:23493751

  9. Evidence of the enhancement effect in electrical stimulation via electrode matching (L)

    PubMed Central

    Goupell, Matthew J.; Mostardi, Mitchell J.

    2012-01-01

    The ability to match a pulsing electrode during multi-electrode stimulation through a research interface was measured in seven cochlear-implant (CI) users. Five listeners were relatively good at the task and two could not perform the task. Performance did not vary as a function of the number of electrodes or stimulation level. Performance on the matching task was not correlated to performance on an electrode-discrimination task. The listeners may have experienced the auditory enhancement effect, and this may have implications for speech recognition in noise for CI users. PMID:22352475

  10. Evidence of the enhancement effect in electrical stimulation via electrode matching (L).

    PubMed

    Goupell, Matthew J; Mostardi, Mitchell J

    2012-02-01

    The ability to match a pulsing electrode during multi-electrode stimulation through a research interface was measured in seven cochlear-implant (CI) users. Five listeners were relatively good at the task and two could not perform the task. Performance did not vary as a function of the number of electrodes or stimulation level. Performance on the matching task was not correlated to performance on an electrode-discrimination task. The listeners may have experienced the auditory enhancement effect, and this may have implications for speech recognition in noise for CI users. PMID:22352475

  11. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Characterization of oscillatory changes in hippocampus and amygdala after deep brain stimulation of the infralimbic prefrontal cortex.

    PubMed

    Cervera-Ferri, Ana; Teruel-Martí, Vicent; Barceló-Molina, Moises; Martínez-Ricós, Joana; Luque-García, Aina; Martínez-Bellver, Sergio; Adell, Albert

    2016-07-01

    Deep brain stimulation (DBS) is a new investigational therapy that has generated positive results in refractory depression. Although the neurochemical and behavioral effects of DBS have been examined, less attention has been paid to the influence of DBS on the network dynamics between different brain areas, which could contribute to its therapeutic effects. Herein, we set out to identify the effects of 1 h DBS in the infralimbic cortex (IL) on the oscillatory network dynamics between hippocampus and basolateral amygdala (BLA), two regions implicated in depression and its treatment. Urethane-anesthetized rats with bilaterally implanted electrodes in the IL were exposed to 1 h constant stimulation of 130 Hz of frequency, 60 μA of constant current intensity and biphasic pulse width of 80 μsec. After a period of baseline recording, local field potentials (LFP) were recorded with formvar-insulated stainless steel electrodes. DBS of the IL increased the power of slow wave (SW, <1.5 Hz) and theta (3-12 Hz) frequencies in the hippocampus and BLA Furthermore, IL DBS caused a precise coupling in different frequency bands between both brain structures. The increases in SW band synchronization in hippocampus and BLA after DBS suggest that these changes may be important for the improvement of depressive behavior. In addition, the augmentation in theta synchrony might contribute to improvement in emotional and cognitive processes. PMID:27449812

  15. Deep Brain Stimulation: More Complex than the Inhibition of Cells and Excitation of Fibers.

    PubMed

    Florence, Gerson; Sameshima, Koichi; Fonoff, Erich T; Hamani, Clement

    2016-08-01

    High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a "functional inhibition" of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation "local inhibition" and "distant excitation" is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS. PMID:26150316

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. 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.

  19. Capacitor electrode stimulates nerve or muscle without oxidation-reduction reactions.

    PubMed

    Guyton, D L; Hambrecht, F T

    1973-07-01

    Porous tantalum disks, available as "slugs" from the capacitor industry, have large available surface area and a thin insulating coating of tantalum pentoxide. When implanted, they fill with extracellular fluid and operate as capacitor-stimulating electrodes having high capacitance per unit volume. Capable of stimulating excitable tissute without generating electrochemical by-products, these electrodes should provide a safer interface between neural prosthetic devices and human tissue. PMID:4197450

  20. 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

  1. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Mueller, Jerel K.; Grill, Warren M.

    2013-06-01

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

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

    PubMed

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

    2014-11-01

    The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD. PMID:24514569

  6. 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.

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  9. Effects of electrode configuration and place of stimulation on speech perception with cochlear prostheses.

    PubMed

    Pfingst, B E; Franck, K H; Xu, L; Bauer, E M; Zwolan, T A

    2001-06-01

    Recent research and clinical experience with cochlear implants suggest that subjects' speech recognition with monopolar or broad bipolar stimulation might be equal to or better than that obtained with narrow bipolar stimulation or other spatially restricted electrode configurations. Furthermore, subjects often prefer the monopolar configurations. The mechanisms underlying these effects are not clear. Two hypotheses are (a) that broader configurations excite more neurons resulting in a more detailed and robust neural representation of the signal and (b) that broader configurations achieve a better spatial distribution of the excited neurons. In this study we compared the effects of electrode configuration and the effects of longitudinal placement and spacing of the active electrodes on speech recognition in human subjects. We used experimental processor maps consisting of 11 active electrodes in a 22-electrode scala tympani array. Narrow bipolar (BP), wide bipolar (BP + 6), and monopolar (MP2) configurations were tested with various locations of active electrodes. We tested basal, centered, and apical locations (with adjacent active electrodes) and spatially distributed locations (with every other electrode active) with electrode configuration held constant. Ten postlingually deafened adult human subjects with Nucleus prostheses were tested using the SPEAK processing strategy. The effects of electrode configuration and longitudinal place of stimulation on recognition of CNC phonemes and words in quiet and CUNY sentences in noise (+10 dB S/N) were similar. Both independent variables had large effects on speech recognition and there were interactions between these variables. These results suggest that the effects of electrode configuration on speech recognition might be due, in part, to differences among the various configurations in the spatial location of stimulation. Correlations of subjective judgments of sound quality with speech-recognition ability were moderate

  10. 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

  11. 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

  12. Optimum electrode geometry for spinal cord stimulation: the narrow bipole and tripole.

    PubMed

    Holsheimer, J; Wesselink, W A

    1997-09-01

    A computer model is used to calculate the optimum geometry of an epidural electrode, consisting of a longitudinal contact array, for spinal cord stimulation in the management of chronic, intractable pain. 3D models of the spinal area are used for the computation of stimulation induced fields, and a cable model of myelinated nerve fibre is used for the calculation of the threshold stimulus to excite large dorsal column and dorsal root fibres. The criteria for the geometry of the longitudinal contact array are: a low threshold for the stimulation of dorsal column fibres compared with dorsal root fibres; and a low stimulation voltage (and current). For both percutaneous and laminectomy electrodes, the contact length should be approximately 1.5 mm, and the optimum contact separation, as determined by the computer model, is 2-2.5 mm. The contacts for a laminectomy electrode should be approximately 4 mm wide. This electrode geometry is applicable to all spinal levels where the dorsal columns can be stimulated (C1-2 down to L1). The stimulating electrode should preferably be used as a tripole with one (central) cathode. PMID:9374053

  13. 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

  14. Direct bladder stimulation with suture electrodes promotes voiding in a spinal animal model: a technical report.

    PubMed

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

    1997-01-01

    To determine the efficacy of a new electrode for direct bladder stimulation, five male cats were instrumented during anesthesia. Multistranded, 316LVM, stainless-steel, wire electrodes were implanted on the bladder wall serosa above the trigone area. The electrodes were made with a needle attached to the end that was cut off after suturing the electrode in place. Additional instrumentation included tubes for pressure recording and filling, and hook electrodes for leg and pelvic floor EMG recording. Bladder filling and stimulation studies were conducted in tethered animals 1 to 2 weeks following recovery. Chronic studies were conducted following recovery in tethered animals. To test these electrodes in a spinal cord injury (SCI) model, a T-1 level complete lesion was performed on the above instrumented animals. Spinal animals had successful direct bladder stimulation that induced active contractions and voiding both before and after SCI, but voiding rates were higher more than 2 weeks after SCI and at larger initial bladder volumes. Optimum stimulation parameters consisted of 40 pulses per second, 300 microseconds to 1 ms pulse duration, a stimulation period of 3 to 4 s, and 10 to 40 mA. Urethral resistance, indicated by a urethral function measure, showed that stimulation had no adverse effect on urethral function, and fluoroscopy showed an open membranous urethra during stimulation and voiding. The cat has a small penile urethra that is the flow rate controlling zone. The suture electrode did not corrode, erode into the bladder, or become dislodged, and appears suitable for chronic implantation. PMID:9021627

  15. Clinical experience with reinforced, anchored intramuscular electrodes for functional neuromuscular stimulation.

    PubMed

    Prochazka, A; Davis, L A

    1992-05-01

    Implanted intramuscular electrodes must remain functional for many years if functional neuromuscular stimulation (FNS) is to become a standard treatment in paralysed individuals. In initial trials we found that 5 of 11 coiled single-wire FNS electrodes implanted in 3 patients failed within 8 months. Consequently, we turned to a reinforced electrode comprising 2 multi-stranded, insulated wires tandem-wound on a prolene core and terminated by a prolene anchor or tine (after Mortimer et al., 1986, 1987). The electrodes were implanted with a translumbar aortogram needle, the teflon sheath of which enabled us to stimulate through the tip to guide placement. We have monitored the electrical and functional properties of 8 reinforced electrodes implanted in 2 incomplete quadriplegic patients over 22 months. Four of the electrodes were used for at least 1 h daily to exercise muscles or to provide FNS in gait. Electrical impedances, thresholds and elicited limb motion remained constant in all 8 electrodes over the test period. Disadvantages of the reinforced electrodes are (1) difficulty of eventual removal, and (2) risk of pathogenic infiltration is increased by the 3-filament structure (fortunately dense tissue encapsulation seems to mitigate infection). We conclude that tandem-wound, prolene-reinforced FNS electrodes are much more robust than previous single-coil designs and may form the basis for FNS devices of the future. PMID:1501502

  16. 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

  17. Fascicular selectivity in transverse stimulation with a nerve cuff electrode: a theoretical approach.

    PubMed

    Deurloo, Kirsten E I; Holsheimer, Jan; Bergveld, Piet

    2003-10-01

    The performance of cathode-anode configurations in a cuff electrode to stimulate a single fascicle in a nerve trunk has been investigated theoretically. A three-dimensional volume conductor model of a nerve trunk with four fascicles in a cuff electrode and a model of myelinated nerve fiber stimulation were used to calculate the recruitment of 15 m fibers in each fascicle. The effect of a monopole, a transverse bipole (anode opposite the cathode), and a narrow transverse tripole (guarded cathode) in selectively stimulating 15 m fibers in each fascicle has been quantified and presented as recruitment curves. It is predicted that selective fascicle stimulation is advanced most by stimulation with a bipole in a plane perpendicular to the axis of the nerve trunk. Monopoles and conventional longitudinal tripoles perform less well, as does a longitudinal tripole with an additional "steering" anode. Apart from transverse bipolar stimulation an additional anode may be used to maximally fit the area of excitation to the topography of the fascicle to be recruited. As compared to monopolar and longitudinal tripolar stimulation, the slope of the recruitment curves in transverse bipolar stimulation is reduced considerably, thus allowing improved fine tuning of nerve (and thus force) recruitment. Another advantage of this method is a minimal number of cable connections to the cuff electrode. The cost of the improved selectivity is an increased stimulation current. PMID:22151073

  18. Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats

    PubMed Central

    Alam, Monzurul; Garcia-Alias, Guillermo; Shah, Prithvi K.; Gerasimenko, Yury; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

    2015-01-01

    Background Epidural spinal cord stimulation is a promising technique for modulating the level of excitability and reactivation of dormant spinal neuronal circuits after spinal cord injury (SCI). We examined the ability of chronically implanted epidural stimulation electrodes within the cervical spinal cord to (1) directly elicit spinal motor evoked potentials (sMEPs) in forelimb muscles and (2) determine whether these sMEPs can serve as a biomarker of forelimb motor function after SCI. New method We implanted EMG electrodes in forelimb muscles and epidural stimulation electrodes at C6 and C8 in adult rats. After recovering from a dorsal funiculi crush (C4), rats were tested with different stimulation configurations and current intensities to elicit sMEPs and determined forelimb grip strength. Results: sMEPs were evoked in all muscles tested and their characteristics were dependent on electrode configurations and current intensities. C6(−) stimulation elicited more robust sMEPs than stimulation at C8(−). Stimulating C6 and C8 simultaneously produced better muscle recruitment and higher grip strengths than stimulation at one site. Comparison with existing method(s) Classical method to select the most optimal stimulation configuration is to empirically test each combination individually for every subject and relate to functional improvements. This approach is impractical, requiring extensively long experimental time to determine the more effective stimulation parameters. Our proposed method is fast and physiologically sound. Conclusions Results suggest that sMEPs from forelimb muscles can be useful biomarkers for identifying optimal parameters for epidural stimulation of the cervical spinal cord after SCI. PMID:25791014

  19. 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

  20. Electrical stimulation with multichannel electrodes in deaf patients.

    PubMed

    Burian, K; Hochmair, E; Hochmair-Desoyer, I; Lessel, M R

    1980-01-01

    Design and function of a 6- or 8-channel electrode assembly, which was introduced through the round window into the scala tympani, are described. Two different receiver systems, a more simple one with reed contacts and a more complex one in hybrid technology, are also described. Signal and energy are delivered transcutaneously via inductively coupled coils. The results of the electrical tests are described and discussed. PMID:6892764

  1. 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

  2. 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 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

  3. BaroLoop: using a multichannel cuff electrode and selective stimulation to reduce blood pressure.

    PubMed

    Plachta, Dennis T T; Gierthmuehlen, Mortimer; Cota, Oscar; Boeser, Fabian; Stieglitz, Thomas

    2013-01-01

    The therapy of refractory hypertension is an increasing problem for health care systems and a frontend in research in both pharmacology and neuroelectronic engineering. Overriding the baroreceptive information of afferent nerve fibers, originating from pressure sensors in the aortic arch, can trigger the baroreflex, a systemic control system that lowers the blood pressure (BP) almost instantaneously. Using a multichannel cuff electrode, wrapped around a rat vagal nerve, we were able to regulate the BP using selective, tripolar stimulation. The tripolar stimulation was sufficiently selective to not trigger any unwanted side effects like bradycardia or bradypnea. The BP was reduced best with charge balanced stimulation amplitudes of 1 mA and pulse duration of 0.3 ms. The stimulation frequency had only a mild influence on the effectiveness of the stimulation and did work best at 40 Hz. We found that the BP took up to five times the stimulation period to recover to the value prior to stimulation. PMID:24109797

  4. 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.

  5. Binaural release from masking with single- and multi-electrode stimulation in children with cochlear implants.

    PubMed

    Todd, Ann E; Goupell, Matthew J; Litovsky, Ruth Y

    2016-07-01

    Cochlear implants (CIs) provide children with access to speech information from a young age. Despite bilateral cochlear implantation becoming common, use of spatial cues in free field is smaller than in normal-hearing children. Clinically fit CIs are not synchronized across the ears; thus binaural experiments must utilize research processors that can control binaural cues with precision. Research to date has used single pairs of electrodes, which is insufficient for representing speech. Little is known about how children with bilateral CIs process binaural information with multi-electrode stimulation. Toward the goal of improving binaural unmasking of speech, this study evaluated binaural unmasking with multi- and single-electrode stimulation. Results showed that performance with multi-electrode stimulation was similar to the best performance with single-electrode stimulation. This was similar to the pattern of performance shown by normal-hearing adults when presented an acoustic CI simulation. Diotic and dichotic signal detection thresholds of the children with CIs were similar to those of normal-hearing children listening to a CI simulation. The magnitude of binaural unmasking was not related to whether the children with CIs had good interaural time difference sensitivity. Results support the potential for benefits from binaural hearing and speech unmasking in children with bilateral CIs. PMID:27475132

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

    PubMed Central

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

    2011-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Koehne, Jessica E.

    2016-01-01

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

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

    PubMed

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

    2013-05-15

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n=24) or sham surgery (n=24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions. PMID:23434606

  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. Stimulation of the Rat Subthalamic Nucleus is Neuroprotective Following Significant Nigral Dopamine Neuron Loss

    PubMed Central

    Spieles-Engemann, A. L.; Behbehani, M. M.; Collier, T. J.; Wohlgenant, S. L.; Steece-Collier, K.; Paumier, K.; Daley, B. F.; Gombash, S.; Madhavan, L.; Mandybur, G. T.; Lipton, J.W.; Terpstra, B.T.; Sortwell, C.E.

    2010-01-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson’s disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between two and four weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief. PMID:20307668

  11. Effects of STN DBS on Rigidity in Parkinson’s 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 Parkinson’s 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 Parkinson’s 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

  12. Microstimulators and Intramuscular Hook Electrodes for the Stimulation of Respiratory Muscles

    PubMed Central

    Walter, James S; Dunn, Robert B; Wurster, Robert D; Laghi, Franco

    2007-01-01

    Background/Objectives: We determined the feasibility of stimulating the major muscles of respiration with different types of electrodes. Intramuscular hook electrodes, model microstimulators (M-Micro) developed in our laboratory, and commercial radiofrequency microstimulators (RFM) (Alfred Mann Foundation, Valencia, CA), were employed in this investigation. Methods: In 8 anesthetized dogs, M-Micro were placed bilaterally on the diaphragm and in the abdominal muscles, and hook electrodes were placed in the 3rd and 5th intercostal regions adjacent to the intercostal nerves known to support inspiration. In 3 of the 8 animals, RFMs (Alfred Mann Foundation) in addition to the M-Micros were sutured to each hemidiaphragm at the same optimal site for phrenic nerve stimulation. During a hyperventilation-induced apnea, 2-second stimulations were applied to the diaphragm and with various combinations of diaphragm plus supporting muscles, both thoracic and abdominal. Results: Diaphragm stimulation alone provided tidal volumes adequate for basal alveolar ventilation. However, implantation of the RFM required greater contact with the muscle. Stimulating other respiratory muscles along with the diaphragm further increased tidal volumes. The hook electrodes, M-Micro, and RFM performed equally well. Conclusions: In the acute dog model, M-Micro and hook electrodes can provide an implant system for the maintenance of ventilation. Support of the intercostal and abdominal muscles has the potential to reduce the contraction requirements of the diaphragm with decreased likelihood of diaphragm fatigue and hypoventilation. Whether the electrodes under investigation could provide an implant system for long-term ventilation needs to be determined. PMID:17853655

  13. 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

  14. Nerve stimulation with a multi-contact cuff electrode: validation of model predictions.

    PubMed

    Deurloo, K E; Holsheimer, J; Bergveld, P

    2000-10-01

    The recruitment characteristics of muscle selective nerve stimulation by a multi-contact nerve cuff electrode, as predicted by computer modeling, have been investigated in acute experiments on rabbits. A nerve cuff containing five or six dot electrodes was placed around the sciatic nerve in five rabbits. M-waves were recorded with wire electrodes from the lateral gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. The muscle recruitment performances of three contact configurations (monopole, transverse bipole, transverse tripole) were compared. The selectivity was quantified by the recruitment of two muscles (one extensor and one flexor) in response to a particular stimulus. The results showed that only in a few cases, transverse bi- and tripolar stimulation provided a better selectivity than monopolar stimulation. Neither of the two extensors, nor of the two flexors could be stimulated separately. In accordance with the results of the modeling studies, bi- and tripolar stimulation required higher stimulus currents than monopolar stimulation, whereas maximum recruitment and slopes of recruitment curves were lower. The rabbit sciatic nerve appears to be a less suitable preparation for reproducible selectivity experiments, due to the variability in the number and size of the fascicles and their position in this nerve. PMID:11094386

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

    NASA Astrophysics Data System (ADS)

    Jain, Shilpee; Sharma, Ashutosh; Basu, Bikramjit

    2014-03-01

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

  16. Analysis of spinal cord stimulation and design of epidural electrodes by computer modeling.

    PubMed

    Holsheimer, J; Struijk, J J; Wesselink, W A

    1998-01-01

    This paper is an overview of the results of computer modeling of spinal cord stimulation, started ten years ago at the University of Twente, The Netherlands. Results are given of the analysis of various geometrical factors, including spinal anatomy, which influence the effect of spinal cord stimulation on nerve fiber recruitment and paresthesia coverage. In a second phase, the computer model was used for the design of new electrode configurations expected to give a better paresthesia coverage in the management of chronic pain. Two new electrode types are presented: the narrow bi-/tripole and the transverse tripole. The latter also enables adjusting the body area affected with paresthesia by means of a dual channel pulse generator giving simultaneous pulses, thereby limiting surgical interventions for electrode repositioning. PMID:22150882

  17. Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

    PubMed

    Morrison, C E; Borod, J C; Perrine, K; Beric, A; Brin, M F; Rezai, A; Kelly, P; Sterio, D; Germano, I; Weisz, D; Olanow, C W

    2004-03-01

    The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery. PMID:15010083

  18. A tripolar current-steering stimulator ASIC for field shaping in deep brain stimulation.

    PubMed

    Valente, Virgilio; Demosthenous, Andreas; Bayford, Richard

    2012-06-01

    A significant problem with clinical deep brain stimulation (DBS) is the high variability of its efficacy and the frequency of side effects, related to the spreading of current beyond the anatomical target area. This is the result of the lack of control that current DBS systems offer on the shaping of the electric potential distribution around the electrode. This paper presents a stimulator ASIC with a tripolar current-steering output stage, aiming at achieving more selectivity and field shaping than current DBS systems. The ASIC was fabricated in a 0.35-μ m CMOS technology occupying a core area of 0.71 mm(2). It consists of three current sourcing/sinking channels. It is capable of generating square and exponential-decay biphasic current pulses with five different time constants up to 28 ms and delivering up to 1.85 mA of cathodic current, in steps of 4 μA, from a 12 V power supply. Field shaping was validated by mapping the potential distribution when injecting current pulses through a multicontact DBS electrode in saline. PMID:23853142

  19. 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.

  20. 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

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

    PubMed

    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

  2. A computational model for bipolar deep brain stimulation of the subthalamic nucleus.

    PubMed

    Iacono, Maria I; Neufeld, Esra; Bonmassar, Giorgio; Akinnagbe, Esther; Jakab, Andras; Cohen, Ethan; Kuster, Niels; Kainz, Wolfgang; Angelone, Leonardo M

    2014-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to reduce some of the symptoms of advanced, levodopa-responsive Parkinson's disease that are not adequately controlled with medication. However, the precise mechanism of the therapeutic action of DBS is still unclear. Stimulation-induced side effects are not uncommon and require electrical "dose" adjustments. Quantitative methods are needed to fully characterize the electric field in the deep brain region that surrounds the electrodes in order to help with adjustments and maximize the efficacy of the device. Herein we report a magnetic resonance imaging (MRI)-based head model proposed for analysis of fields generated by deep brain stimulation (DBS). The model was derived from multimodal image data at 0.5mm isotropic spatial resolution and distinguishes 142 anatomical structures, including the basal ganglia and 38 nuclei of the thalamus. Six bipolar electrode configurations (1-2, 1-3, 1-4, 2-3, 2-4, 3-4) were modeled in order to assess the effects of the inter-electrode distance of the electric field. Increasing the distance between the electrodes results in an attenuated stimulation, with up to 25% reduction in electric field amplitude delivered (2-3 vs. 1-4). The map of the deep brain structures provided a highly precise anatomical detail which is useful for the quantitative assessment of current spread around the electrode and a better evaluation of the stimulation setting for the treatment optimization. PMID:25571427

  3. In vitro stimulation of neurons by a planar Ti-Au-electrode interface

    NASA Astrophysics Data System (ADS)

    Reiher, A.; Günther, S.; Krtschil, A.; Witte, H.; Krost, A.; Opitz, T.; de Lima, A.; Voigt, T.

    2005-03-01

    We report on the realization of a planar large area electrode interface which reproducibly allows the global excitation of neurons and the generation of stimulated network activity. The interface is formed by two double finger-shaped Ti-Au-electrodes without any isolating coating deposited by electron beam evaporation on microscope cover slips. Dissociated nerve cells from embryonic rat cerebral cortex were cultured on these electrodes forming electrophysiologically active networks within seven days of culture. These networks were electrically excited by application of voltage pulses, resulting either in an activity of single neurons or in a stimulated synchronous network activity in dependence on the pulse parameters. The impact of these parameters, such as the number of pulses, the pulse amplitude and the delay between distinct pulse events, on the stimulation success was systematically investigated. We found threshold values for the voltage pulse amplitude of 1.8-2.2 V and for the voltage pulse duration of 1 ms to reproducibly obtain stimulation success with our system. These results are repeated for differently aged cell cultures and at different sections of the whole network. The stimulation procedure does not significantly damage the nerve cells.

  4. 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

  5. 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

  6. Optimization of Thin-Film Configuration for Light-Addressable Stimulation Electrode

    NASA Astrophysics Data System (ADS)

    Suzurikawa, Jun; Kanzaki, Ryohei; Nakao, Masayuki; Jimbo, Yasuhiko; Takahashi, Hirokazu

    Light addressing is an emerging technique to optically address a virtual electrode on a photoconductive substrate. A thinner photoconductive layer of a light-addressable planar electrode can improve the spatial resolution of the light-addressed electrode. Voltage application to the electrode, however, causes strong electric field across the thin photoconductive layer with a significant avalanche effect, which induces undesired increase of dark current. Here, in order to overcome this problem, we investigated how photoconductive-layer thickness and passivation-layer conductivity impact on voltage-application-induced bright and dark charge densities. Consequently, suppression of dark charge density with thick photoconductive layer and low-conductive passivation layer is a key factor for optimization of light-addressable electrode. With this designing strategy, we developed a novel light-addressable electrode using titanium dioxide as photoconductor. To suppress avalanche effect, the thickness of the titanium-dioxide layer was designed to be 1.5 μm. The fabricated electrode turned out to have a sufficient photoelectric property; the bright charge density reached up to 70 μC/cm2 and the bright to dark charge density ratio, over 10, which can realize stimulation to cultured dissociated neurons.

  7. 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

    2016-01-01

    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

  8. Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: a review of the literature.

    PubMed

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

    2012-01-01

    Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. 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 sex, and/or early-onset PD. 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 mechanisms 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 toward development of future DBS mood-stabilization therapies. PMID:22450620

  9. 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

  10. Effects of Vestibular Prosthesis Electrode Implantation and Stimulation on Hearing in Rhesus Monkeys

    PubMed Central

    Dai, Chenkai; Fridman, Gene Y.; Della Santina, Charles C.

    2011-01-01

    To investigate the effects of vestibular prosthesis electrode implantation and activation on hearing in rhesus monkeys, we measured auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) in four rhesus monkeys before and after unilateral implantation of vestibular prosthesis electrodes in each of 3 left semicircular canals (SCC). Each of the 3 left SCCs were implanted with electrodes via a transmastoid approach. Right ears, which served as controls, were not surgically manipulated. Hearing tests were conducted before implantation (BI) and then 4 weeks post implantation both without electrical stimulation (NS) and with electrical stimulation (S). During the latter condition, prosthetic electrical stimuli encoding 3 dimensions of head angular velocity were delivered to the 3 ampullary branches of the left vestibular nerve via each of 3 electrode pairs of a multichannel vestibular prosthesis. Electrical stimuli comprised charge-balanced biphasic pulses at a baseline rate of 94 pulses/sec, with pulse frequency modulated from 48–222 pulses/s by head angular velocity. ABR hearing thresholds to clicks and tone pips at 1, 2, and 4 kHz increased by 5–10 dB from BI to NS and increased another ~5 dB from NS to S in implanted ears. No significant change was seen in right ears. DPOAE amplitudes decreased by 2–14 dB from BI to NS in implanted ears. There was a slight but insignificant decrease of DPOAE amplitude and a corresponding increase of DPOAE/Noise floor ratio between NS and S in implanted ears. Vestibular prosthesis electrode implantation and activation have small but measurable effects on hearing in rhesus monkeys. Coupled with the clinical observation that patients with cochlear implants only rarely exhibit signs of vestibular injury or spurious vestibular nerve stimulation, these results suggest that although implantation and activation of multichannel vestibular prosthesis electrodes in human will carry a risk of hearing loss

  11. 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.

  12. Flexible, high-density microphotodiode array with integrated sputtered iridium oxide electrodes for retinal stimulation

    NASA Astrophysics Data System (ADS)

    Yang, Frank; Chang, Mao-Yen; Yang, Chung-Hua; Teng, Chih-Ciao; Fan, Long-Sheng

    2016-01-01

    To assess the charge-injection capacity of the sputtered iridium oxide film (SIROF) electrode on the retinal CMOS image sensor (CIS) chip, a polyimide-based flex device was designed and fabricated to package the retinal CIS chip. The polyimide-flex-based packaging process keeps the surface of photosensors clean, and the measured connection resistance meets the packaging requirement of the low-power retinal CIS chip. The in vitro experimental results show that the small SIROF electrodes can provide a biphasic charge injection per phase of 3.9 nC/ph to achieve the stimulation threshold at a polarization potential of -0.44 V.

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

    PubMed Central

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

    2013-01-01

    Brain-machine interfaces (BMIs) that can precisely monitor and control neural activity will likely require new hardware with improved resolution and specificity. New nanofabricated electrodes with feature sizes and densities comparable to neural circuits may lead to such improvements. In this perspective, we review the recent development of vertical nanowire (NW) electrodes that could provide highly parallel single-cell recording and stimulation for future BMIs. We compare the advantages of these devices and discuss some of the technical challenges that must be overcome for this technology to become a platform for next-generation closed-loop BMIs. PMID:23486552

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  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. 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

  17. 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 (Q(inj), i.e., electrochemical capacitance). Most traditional electrodes tend to have low Q(inj) 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

  18. Deep brain stimulation for chronic pain.

    PubMed

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

    2015-10-01

    Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome. PMID:26122383

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

    PubMed Central

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

    2013-01-01

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

  20. Post-operative imaging in deep brain stimulation: A controversial issue.

    PubMed

    Saleh, Christian; Dooms, Georges; Berthold, Christophe; Hertel, Frank

    2016-08-01

    In deep brain stimulation (DBS), post-operative imaging has been used on the one hand to assess complications, such as haemorrhage; and on the other hand, to detect misplaced contacts. The post-operative determination of the accurate location of the final electrode plays a critical role in evaluating the precise area of effective stimulation and for predicting the potential clinical outcome; however, safety remains a priority in postoperative DBS imaging. A plethora of diverse post-operative imaging methods have been applied at different centres. There is neither a consensus on the most efficient post-operative imaging methodology, nor is there any standardisation for the automatic or manual analysis of the images within the different imaging modalities. In this article, we give an overview of currently applied post-operative imaging modalities and discuss the current challenges in post-operative imaging in DBS. PMID:27029393

  1. 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

  2. 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

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

    PubMed

    Montgomery, Erwin B; He, Huang

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  5. 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

  6. 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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2013-01-01

    In recent years, there has been significant growth in the use of patient-specific models to predict the effects of neuromodulation therapies such as deep brain stimulation (DBS). However, translating these models from a research environment to the everyday clinical workflow has been a challenge, primarily due to the complexity of the models and the expertise required in specialized visualization software. In this paper, we deploy the interactive visualization system ImageVis3D Mobile, which has been designed for mobile computing devices such as the iPhone or iPad, in an evaluation environment to visualize models of Parkinson's disease patients who received DBS therapy. Selection of DBS settings is a significant clinical challenge that requires repeated revisions to achieve optimal therapeutic response, and is often performed without any visual representation of the stimulation system in the patient. We used ImageVis3D Mobile to provide models to movement disorders clinicians and asked them to use the software to determine: 1) which of the four DBS electrode contacts they would select for therapy; and 2) what stimulation settings they would choose. We compared the stimulation protocol chosen from the software versus the stimulation protocol that was chosen via clinical practice (independent of the study). Lastly, we compared the amount of time required to reach these settings using the software versus the time required through standard practice. We found that the stimulation settings chosen using ImageVis3D Mobile were similar to those used in standard of care, but were selected in drastically less time. We show how our visualization system, available directly at the point of care on a device familiar to the clinician, can be used to guide clinical decision making for selection of DBS settings. In our view, the positive impact of the system could also translate to areas other than DBS. PMID:22450824

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

    SciTech Connect

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

    2009-11-15

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

  10. Future of brain stimulation: new targets, new indications, new technology.

    PubMed

    Hariz, Marwan; Blomstedt, Patric; Zrinzo, Ludvic

    2013-11-01

    In the last quarter of a century, DBS has become an established neurosurgical treatment for Parkinson's disease (PD), dystonia, and tremors. Improved understanding of brain circuitries and their involvement in various neurological and psychiatric illnesses, coupled with the safety of DBS and its exquisite role as a tool for ethical study of the human brain, have unlocked new opportunities for this technology, both for future therapies and in research. Serendipitous discoveries and advances in structural and functional imaging are providing abundant "new" brain targets for an ever-increasing number of pathologies, leading to investigations of DBS in diverse neurological, psychiatric, behavioral, and cognitive conditions. Trials and "proof of concept" studies of DBS are underway in pain, epilepsy, tinnitus, OCD, depression, and Gilles de la Tourette syndrome, as well as in eating disorders, addiction, cognitive decline, consciousness, and autonomic states. In parallel, ongoing technological development will provide pulse generators with longer battery longevity, segmental electrode designs allowing a current steering, and the possibility to deliver "on-demand" stimulation based on closed-loop concepts. The future of brain stimulation is certainly promising, especially for movement disorders-that will remain the main indication for DBS for the foreseeable future-and probably for some psychiatric disorders. However, brain stimulation as a technique may be at risk of gliding down a slippery slope: Some reports indicate a disturbing trend with suggestions that future DBS may be proposed for enhancement of memory in healthy people, or as a tool for "treatment" of "antisocial behavior" and for improving "morality." PMID:24123327

  11. Bifocal cortical electrical stimulation for pain by interdural implantation of the electrodes.

    PubMed

    Sakas, Damianos E; Flaskas, Theofanis N; Panourias, Ioannis G; Georgakoulias, Nikolaos

    2011-01-01

    Chronic electrical cortical stimulation (ECS) is an evolving therapy for alleviating treatment-refractory chronic pain syndromes. In this report, the authors describe a modified technique of ECS that involves resection of dural strips and interdural placement of the electrodes as a patch, and bifocal stimulation by implanting 2 electrode strips, that is, one over the motor and one over the sensory cortices. The technique was used in 4 patients with treatment-refractory pain syndromes: a 76-year-old woman with poststroke central pain, 2 women, (71 and 73 years old) with trigeminal pain, and a 44-year-old man with phantom limb pain. All 4 patients experienced a sustained significant improvement in the intensity of pain and have gained a substantially improved functionality and quality of life. An important finding in these patients was the constancy of impedance within a narrow values range throughout the postoperative period. For the cases, the follow-up exceeds 24, 15, 12, and 9 months. The factors affecting the efficacy of ECS are discussed. In the authors' opinion, interdural implantation of the electrodes holds the promise to improve the efficacy and consistency of ECS compared with the standard epidural or subdural implantation without increasing the risk of the procedure. The technical considerations and the potential therapeutic advantages of the interdural bifocal approach are discussed. PMID:20597601

  12. Verbal Memory Decline following DBS for Parkinson’s Disease: Structural Volumetric MRI Relationships

    PubMed Central

    Geevarghese, Ruben; Lumsden, Daniel E.; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

    2016-01-01

    Background Parkinson’s disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Objectives Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. Methods A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. Results A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Conclusion Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes. PMID:27557088

  13. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FIXED MICROWAVE SERVICES Multichannel Video Distribution and Data Service Rules for the 12.2-12.7 GHz... ensure that the EPFD from its transmitting antenna at all DBS customers of record locations is below the... in § 101.105(a)(4)(ii). DBS customers of record are those who had their DBS receive...

  14. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false MVDDS protection of DBS. 101.1440 Section 101... Band § 101.1440 MVDDS protection of DBS. (a) An MVDDS licensee shall not begin operation unless it can ensure that the EPFD from its transmitting antenna at all DBS customers of record locations is below...

  15. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false MVDDS protection of DBS. 101.1440 Section 101... Band § 101.1440 MVDDS protection of DBS. (a) An MVDDS licensee shall not begin operation unless it can ensure that the EPFD from its transmitting antenna at all DBS customers of record locations is below...

  16. 47 CFR 101.1440 - MVDDS protection of DBS.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false MVDDS protection of DBS. 101.1440 Section 101... Band § 101.1440 MVDDS protection of DBS. (a) An MVDDS licensee shall not begin operation unless it can ensure that the EPFD from its transmitting antenna at all DBS customers of record locations is below...

  17. 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

  18. 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

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

    PubMed

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

    2012-06-01

    This paper presents an integrated stimulator that can be embedded in implantable electrode books for interfacing with nerve roots at the cauda equina. The Active Book overcomes the limitation of conventional nerve root stimulators which can only support a small number of stimulating electrodes due to cable count restriction through the dura. Instead, a distributed stimulation system with many tripole electrodes can be configured using several Active Books which are addressed sequentially. The stimulator was fabricated in a 0.6-μm high-voltage CMOS process and occupies a silicon area of 4.2 × 6.5 mm(2). The circuit was designed to deliver up to 8 mA stimulus current to tripole electrodes from an 18 V power supply. Input pad count is limited to five (two power and three control lines) hence requiring a specific procedure for downloading stimulation commands to the chip and extracting information from it. Supported commands include adjusting the amplitude of stimulus current, varying the current ratio at the two anodes in each channel, and measuring relative humidity inside the chip package. In addition to stimulation mode, the chip supports quiescent mode, dissipating less than 100 nA current from the power supply. The performance of the stimulator chip was verified with bench tests including measurements using tripoles in saline. PMID:23853144

  20. 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.

  1. 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.

  2. 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

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

    PubMed Central

    Mathias, Lawrence; Thakur, Ajay; Kumar, Dhanesh

    2016-01-01

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

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

    PubMed

    Shanmugam, Sukumar; Mathias, Lawrence; Thakur, Ajay; Kumar, Dhanesh

    2016-04-01

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

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

    SciTech Connect

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

    2009-02-02

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

  6. Multichannel DBS halftoning for improved texture quality

    NASA Astrophysics Data System (ADS)

    Slavuj, Radovan; Pedersen, Marius

    2015-01-01

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

  7. 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.

  8. A Three-dimensional Deformable Brain Atlas for DBS Targeting. I. Methodology for Atlas Creation and Artifact Reduction

    PubMed Central

    Sudhyadhom, Atchar; Okun, Michael S; Foote, Kelly D; Rahman, Maryam; Bova, Frank J

    2012-01-01

    Background: Targeting in deep brain stimulation (DBS) relies heavily on the ability to accurately localize particular anatomic brain structures. Direct targeting of subcortical structures has been limited by the ability to visualize relevant DBS targets. Methods and Results: In this work, we describe the development and implementation, of a methodology utilized to create a three dimensional deformable atlas for DBS surgery. This atlas was designed to correspond to the print version of the Schaltenbrand-Bailey atlas structural contours. We employed a smoothing technique to reduce artifacts inherent in the print version. Conclusions: We present the methodology used to create a three dimensional patient specific DBS atlas which may in the future be tested for clinical utility. PMID:23091579

  9. A neural network-based design of an on-off adaptive control for Deep Brain Stimulation in movement disorders.

    PubMed

    Shukla, Pitamber; Basu, Ishita; Graupe, Daniel; Tuninetti, Daniela; Slavin, Konstantin V

    2012-01-01

    The current Food and Drug Administration approved system for the treatment of tremor disorders through Deep Brain Stimulation (DBS) of the area of the brain that controls movement, operates open-loop. It does not automatically adapt to the instantaneous patient's needs or to the progression of the disease. This paper demonstrates an adaptive closed-loop controlled DBS that, after switching off stimulation, tracks few physiological signals to predict the reappearance of tremor before the patient experiences discomfort, at which point it instructs the DBS controller to switch on stimulation again. The core of the proposed approach is a Neural Network (NN) which effectively extracts tremor predictive information from non-invasively recorded surface-electromyogram(sEMG) and accelerometer signals measured at the symptomatic extremities. A simple feed-forward back-propagation NN architecture is shown to successfully predict tremor in 31 out of 33 trials in two Parkinson's Disease patients with an overall accuracy of 75.8% and sensitivity of 92.3%. This work therefore shows that closed-loop DBS control is feasible in the near future and that it can be achieved without modifications of the electrodes implanted in the brain, i.e., is backward compatible with approved DBS systems. PMID:23366839

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

    PubMed

    Hickey, Patrick; Stacy, Mark

    2016-01-01

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

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

    PubMed Central

    Hickey, Patrick; Stacy, Mark

    2016-01-01

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

  12. Electrodes for high-definition transcutaneous DC stimulation for applications in drug-delivery and electrotherapy, including tDCS

    PubMed Central

    Minhas, Preet; Bansal, Varun; Patel, Jinal; Ho, Johnson S.; Diaz, Julian; Datta, Abhishek; Bikson, Marom

    2010-01-01

    Transcutaneous electrical stimulation is applied in a range of biomedical applications including Transcranial Direct Current Stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-Definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize “high-definition” electrode-gel parameters for electrode durability, skin safety, and subjective pain. Anode and cathode electrode potential, temperature, pH, and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 minutes on agar gel or subject forearms. A selection of 5 types of solid-conductors (Ag pellet, Ag/AgCl pellet, Rubber pellet, Ag/AgCl ring, and Ag/AgCl disc) and 7 conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron, and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and Rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, Rubber, and Ag/AgCl pellet electrodes across all gels. PMID:20488204

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Howell, Bryan; McIntyre, Cameron C.

    2016-06-01

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

  15. Deep brain stimulation in the nucleus ventralis intermedius in patients with essential tremor: habituation of tremor suppression.

    PubMed

    Barbe, Michael T; Liebhart, Lena; Runge, Matthias; Pauls, K Amande M; Wojtecki, Lars; Schnitzler, Alfons; Allert, Niels; Fink, Gereon R; Sturm, Volker; Maarouf, Mohammad; Timmermann, Lars

    2011-03-01

    In patients with essential tremor (ET) already treated with chronic deep brain stimulation (DBS) of the nucleus ventralis intermedius (VIM) we investigated whether optimization of stimulation parameters could improve clinical tremor suppression, and whether this putative effect could be sustained over time. Twenty-three ET patients with VIM-DBS participated in the prospective study. All electrode contacts were tested systematically and stimulation parameters were optimized over the course of 2 days. Clinical tremor rating scale (TRS) was videotaped before, directly after the optimization and at a 10 weeks follow-up and evaluated blindly and independently by two clinicians. For stimulation effect optimization we increased the number of active contacts whereas the total charge applied to the tissue was kept constant. TRS hemi-body scores decreased significantly after optimization. At the 10 weeks follow-up, however, the improvement had faded and was no longer significant. The activities of daily living (ADL) remained significantly improved. Systematic optimization of VIM-DBS parameters in ET patients leads to a short term improvement which habituates over time. Our results provide further evidence for a tolerance effect in chronic VIM stimulation thereby suggesting that frequently alternating stimulation protocols should be tested in future studies of ET patients treated with VIM-DBS. PMID:20927533

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  17. 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

  18. Chronic deep brain stimulation in mesial temporal lobe epilepsy.

    PubMed

    Boëx, Colette; Seeck, Margitta; Vulliémoz, Serge; Rossetti, Andrea O; Staedler, Claudio; Spinelli, Laurent; Pegna, Alan J; Pralong, Etienne; Villemure, Jean-Guy; Foletti, Giovanni; Pollo, Claudio

    2011-07-01

    The objective of this study was to evaluate the efficiency and the effects of changes in parameters of chronic amygdala-hippocampal deep brain stimulation (AH-DBS) in mesial temporal lobe epilepsy (TLE). Eight pharmacoresistant patients, not candidates for ablative surgery, received chronic AH-DBS (130 Hz, follow-up 12-24 months): two patients with hippocampal sclerosis (HS) and six patients with non-lesional mesial TLE (NLES). The effects of stepwise increases in intensity (0-Off to 2 V) and stimulation configuration (quadripolar and bipolar), on seizure frequency and neuropsychological performance were studied. The two HS patients obtained a significant decrease (65-75%) in seizure frequency with high voltage bipolar DBS (≥1 V) or with quadripolar stimulation. Two out of six NLES patients became seizure-free, one of them without stimulation, suggesting a microlesional effect. Two NLES patients experienced reductions of seizure frequency (65-70%), whereas the remaining two showed no significant seizure reduction. Neuropsychological evaluations showed reversible memory impairments in two patients under strong stimulation only. AH-DBS showed long-term efficiency in most of the TLE patients. It is a valuable treatment option for patients who suffer from drug resistant epilepsy and who are not candidates for resective surgery. The effects of changes in the stimulation parameters suggest that a large zone of stimulation would be required in HS patients, while a limited zone of stimulation or even a microlesional effect could be sufficient in NLES patients, for whom the importance of the proximity of the electrode to the epileptogenic zone remains to be studied. Further studies are required to ascertain these latter observations. PMID:21489828

  19. 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

  20. 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.

  1. Deep brain stimulation for movement disorders.

    PubMed

    Larson, Paul S

    2014-07-01

    Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery. PMID:24833244

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

    PubMed

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

    2014-05-01

    ICU patients typically are given large amounts of fluid and often develop oedema. The purpose of this study was to evaluate whether the oedema would change inter-electrode resistance and, thus, require a different approach to using non-invasive electrical stimulation of nerves to assess muscle force. Inter-electrode tissue resistance in the lower leg was measured by applying a 300 µs constant current pulse and measuring the current through and voltage across the stimulating electrodes. The protocol was administered to nine ICU patients with oedema, eight surgical patients without oedema and eight healthy controls. No significant difference in inter-electrode resistance was found between the three groups. For all groups, resistance decreased as stimulation current increased. In conclusion, inter-electrode resistance in ICU patients with severe oedema is the same as the resistance in regular surgical patients and healthy controls. This means that non-invasive nerve stimulation devices do not need to be designed to accommodate different resistances when used with oedema patients; however, surface stimulation does require higher current levels with oedema patients because of the increased distance between the skin surface and the targeted nerve or muscle. PMID:24758395

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

    PubMed

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

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression. PMID:27435420

  4. 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.

  5. Accuracy and safety of targeting using intraoperative "O-arm" during placement of deep brain stimulation electrodes without electrophysiological recordings.

    PubMed

    Sharma, Mayur; Deogaonkar, Milind

    2016-05-01

    The aim of our study was to investigate the accuracy of targeting using intraoperative "O-arm" during deep brain stimulation (DBS) surgery. Intraoperative O-arm (Medtronic, Minneapolis, MN, USA) images were obtained to confirm the accuracy of placement. The difference between intended and actual target coordinates was calculated based on intraoperative images and postoperative CT scan. Euclidian vector error was obtained to estimate the directional error. Correlation of targeting error with the pneumocephalus and the deviation from the planned trajectory was also estimated. Twenty eight DBS leads (globus pallidus internus [GPi], n=13; subthalamic nucleus [STN], n=9; ventralis intermedius nucleus [VIM], n=6) were implanted in 20 patients using the stereotactic Leksell frame (Elekta AB, Stockholm, Sweden) under general anesthesia over a period of 1year. The mean age was 63.6±standard error of the mean (SEM) 15.7years and 60% of patients were males. The mean absolute difference (+SEM) between intended and actual target in x, y and z coordinates based on intraoperative CT scan was 0.65±0.09 (p=0.84), 0.58±0.08 (p=0.98), 1.13±0.10 (p=0.08), respectively, and postoperative (1month) CT scan was 0.82±0.15 (p=0.89), 0.55±0.11 (p=0.97), and 1.58±0.29 (p=0.08), respectively. The Euclidean vector error was 1.59±0.10 and 2.16±0.26 based on intraoperative and postoperative images, respectively. There was no statistically significant targeting error based on fusion of intraoperative CT images to either preoperative CT scan or MRI as registration series, the presence of pneumocephalus, deviation from planned trajectory or the anatomical target (STN versus VIM versus GPi) (p>0.05). Superficial skin infection was encountered in a single patient in this study. The mean total operating room time was 193.5±74.6 minutes. None of the patients required revision in our study. DBS leads can be implanted safely and accurately using intraoperative O-arm with a frame based targeting

  6. Consonant recognition as a function of the number of stimulation channels in the Hybrid short-electrode cochlear implant.

    PubMed

    Reiss, Lina A J; Turner, Christopher W; Karsten, Sue A; Erenberg, Sheryl R; Taylor, Jessica; Gantz, Bruce J

    2012-11-01

    Consonant recognition was measured as a function of the number of stimulation channels for Hybrid short-electrode cochlear implant (CI) users, long-electrode CI users, and normal-hearing (NH) listeners in quiet and background noise. Short-electrode CI subjects were tested with 1-6 channels allocated to a frequency range of 1063-7938 Hz. Long-electrode CI subjects were tested with 1-6, 8, or 22 channels allocated to 188-7938 Hz, or 1-6 or 15 channels from the basal 15 electrodes allocated to 1063-7938 Hz. NH listeners were tested with simulations of each CI group/condition. Despite differences in intracochlear electrode spacing for equivalent channel conditions, all CI subject groups performed similarly at each channel condition and improved up to at least four channels in quiet and noise. All CI subject groups underperformed relative to NH subjects. These preliminary findings suggest that the limited channel benefit seen for CI users may not be due solely to increases in channel interactions as a function of electrode density. Other factors such as pre-operative patient history, location of stimulation in the base versus apex, or a limit on the number of electric channels that can be processed cognitively, may also interact with the effects of electrode contact spacing along the cochlea. PMID:23145621

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-08-01

    We introduce a method to electrically stimulate individual neurons at single-cell resolution in arbitrary spatiotemporal patterns with precise control over stimulation thresholds. By exploiting a custom microelectronic chip, up to 65,000 non-Faradaic electrodes can be uniquely addressed with electrode density exceeding 6500 electrodes mm(-2). We demonstrate extracellular stimulation of dispersed primary hippocampal neuronal cultures using the chip at single-cell resolution. PMID:21725154

  9. STC-DBS Electrical Power Subsystem

    SciTech Connect

    Peck, S.R.; Callen, P.; Pierce, P.; Wylie, T.

    1984-08-01

    The design of the STC-DBS (Satellite Television Corporation - Direct Broadcast Satellite) Electrical Power Subsystem presently under development at RCA Astro-Electronics is highlighted. To efficiently satisfy the payload power requirements, which are dominated by three 220W TWTAs, while at the same time permitting maximum use of already qualified designs, a dual bus system was selected. The payload bus, which operates during non-eclipse periods, is a shunt-regulated solar array bus at 100 volts. The housekeeping bus is regulated at 35.5 volts when sunlit and varies with the battery voltage during eclipse.

  10. 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

  11. 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.

  12. 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.

  13. Active stimulation site of nucleus accumbens deep brain stimulation in obsessive-compulsive disorder is localized in the ventral internal capsule.

    PubMed

    van den Munckhof, Pepijn; Bosch, D Andries; Mantione, Mariska H M; Figee, Martijn; Denys, Damiaan A J P; Schuurman, P Richard

    2013-01-01

    Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by persistent thoughts and repetitive ritualistic behaviours. Despite optimal cognitive-behavioral and pharmacological therapy, approximately 10 % of patients remain treatment-resistant. Deep brain stimulation (DBS) is being investigated as experimental therapy for treatment-refractory OCD. In the current study, we determined the relationship between anatomical location of active electrode contacts and clinical outcome in 16 OCD patients undergoing bilateral nucleus accumbens (NAc) DBS. We found that most patients actually do not receive active stimulation in the NAc but in the more laterally, anteriorly and dorsally located ventral part of the anterior limb of the internal capsule, ventral ALIC (vALIC). Our nine patients receiving bilateral vALIC DBS improved on average 73 % on their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, whereas the six patients with their centers of stimulation located otherwise improved on average only 42 %. We therefore propose bilateral vALIC as a promising new DBS target for patients with treatment-refractory OCD. Future studies employing a direct vALIC targeting approach in larger patient numbers are needed to test whether this proposal holds true. PMID:23652657

  14. 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

  15. Deep Brain Stimulation of the Nucleus Accumbens Shell Attenuates Cue-Induced Reinstatement of Both Cocaine and Sucrose Seeking in Rats

    PubMed Central

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

    2015-01-01

    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 d, with each infusion of cocaine being paired with a cue light. After 21 d 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

  16. 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.

  17. 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.

  18. Pallidal stimulation in dystonia: effects on cognition, mood, and quality of life.

    PubMed

    Hälbig, T D; Gruber, D; Kopp, U A; Schneider, G-H; Trottenberg, T; Kupsch, A

    2005-12-01

    Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) alleviates symptoms in patients with dystonia but its effects on cognition, neuropsychiatric status, and quality of life have not been examined. This is a case series report of 15 consecutive patients with different forms of dystonia who underwent bilateral implantation of DBS electrodes in the GPi. The patients were evaluated preoperatively and after 3-12 months of DBS with tests of cognition (Mattis Dementia Rating Scale, Stroop Test, Trail Making Test, Phonemic and Category Word Fluency, Digit Span, Rey Auditory Verbal Learning Test, Tonic and Phasic Alertness), neuropsychiatric status (Beck Depression and Anxiety Inventories, Montgomery Asberg Depression Rating Scale, Snaith-Hamilton Pleasure Scale, Brief Psychiatric Rating Scale), quality of life, and motor functions. GPi DBS significantly improved dystonic symptoms, functional abilities, and quality of life allowing for a significant reduction of antidystonic medications. No deterioration was observed in cognitive scores and neuropsychiatric measures. The present case series report thus provides preliminary evidence for the safety of GPi DBS regarding cognitive and neuropsychiatric functions in patients with dystonia. PMID:16291900

  19. Health, Happiness and Human Enhancement-Dealing with Unexpected Effects of Deep Brain Stimulation.

    PubMed

    Schermer, Maartje

    2013-01-01

    Deep Brain Stimulation (DBS) is a treatment involving the implantation of electrodes into the brain. Presently, it is used for neurological disorders like Parkinson's disease, but indications are expanding to psychiatric disorders such as depression, addiction and Obsessive Compulsive Disorder (OCD). Theoretically, it may be possible to use DBS for the enhancement of various mental functions. This article discusses a case of an OCD patient who felt very happy with the DBS treatment, even though her symptoms were not reduced. First, it is explored if the argument that 'doctors are not in the business of trading happiness', as used by her psychiatrist to justify his discontinuation of the DBS treatment, holds. The relationship between enhancement and the goals of medicine is discussed and it is concluded that even though the goals of medicine do not set strict limits and may even include certain types of enhancement, there are some good reasons for limiting the kind of things doctors are required or allowed to do. Next, the case is discussed from the perspective of beneficence and autonomy. It is argued that making people feel good is not the same as enhancing their well-being and that it is unlikely-though not absolutely impossible-that the well-being of the happy OCD patient is really improved. Finally, some concerns regarding the autonomy of a request made under the influence of DBS treatment are considered. PMID:24273618

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

    PubMed Central

    Fichtner, Jens; Debove, Ines; Lachenmayer, Lenard; Schüpbach, 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

  1. Transverse versus longitudinal tripolar configuration for selective stimulation with multipolar cuff electrodes.

    PubMed

    Nielsen, Thomas N; Kurstjens, G A Mathijs; Struijk, Johannes J

    2011-04-01

    The ability to stimulate subareas of a nerve selectively is highly desirable, since it has the potential of simplifying surgery to implanting one cuff on a large nerve instead of many cuffs on smaller nerves or muscles, or alternatively can improve function where surgical access to the smaller nerves is limited. In this paper, stimulation was performed with a four-channel multipolar cuff electrode implanted on the sciatic nerve of nine rabbits to compare the extensively researched longitudinal tripolar configuration with the transverse tripolar configuration, which has received less interest. The performance of these configurations was evaluated in terms of selectivity in recruitment of the three branches of the sciatic nerve. The results showed that the transverse configuration was able to selectively activate the sciatic nerve branches to a functionally relevant level in more cases than the longitudinal configuration (20/27 versus 11/27 branches) and overall achieved a higher mean selectivity [0.79 ± 0.13 versus 0.61 ± 0.09 (mean ± standard deviation)]. The transverse configuration was most successful at recruiting the small cutaneous and medium-sized peroneal branches, and less successful at recruiting the large tibial nerve. PMID:21421427

  2. 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

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

    PubMed

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

    2015-02-01

    Considering the functional organization of the subthalamic nucleus (STN), we hypothesized that subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease might have a differential impact on the hypothalamic-pituitary-adrenal axis in relation to the position of active stimulating contact within the STN. In addition, we searched for any STN-DBS-related morning plasma cortisol changes in association with postoperative anxiety and weight gain. A plasma cortisol measurement was performed on the day of initiation of bilateral STN-DBS and repeated after 1 and 17 months in twenty patients with advanced Parkinson's disease. The body weight change and anxiety scores following the implantation were assessed as well. The electrode positions in the STN were determined on T1-weighted magnetic resonance images. After initiation of stimulation, cortisol levels significantly decreased and the cortisol changes after 1 and 17 months strongly correlated with the position of active contact in the subthalamic area. Patients with at least one contact located more medially in the STN experienced a significantly greater decrease of cortisol than those with one or both active contacts more laterally. Furthermore, the lower cortisol levels were strongly associated with higher trait anxiety and weight gain. These changes mimicked the effects of chronic stress and suggest the disturbing impact of STN-DBS on limbic and motivational systems. PMID:25554999

  4. Delayed cerebritis after bilateral stereotactic implantation of globus pallidus interna electrodes for treatment of dystonia.

    PubMed

    Jankowski, Pawel P; Lessig, Stephanie; Nguyen, Andrew D; Barba, David

    2013-01-01

    Deep brain stimulation (DBS) is being used to treat an increasing number of movement and psychiatric disorders. However, the risk of infection remains as a problem that can hinder the usefulness of this technology. We report a case of a patient with dystonia who underwent bilateral globus pallidus interna electrode and impulse generator (IPG) placement, developed an infection of his IPG, and later cerebritis. The patient was initially treated with antibiotics and partial hardware removal. Follow-up cranial imaging showed an area concerning for cerebritis around one of the intracranial electrodes. The patient was then treated with complete hardware removal followed by a course of intravenous antibiotics. Four-month follow-up imaging showed resolution of the infection. This case demonstrates the importance of following cranial imaging in DBS patients with delayed infection, continued vigilance for infection in implanted patients and that partial hardware removal may not be successful in the setting of methicillin-sensitive Staphylococcus aureus infections. PMID:23378545

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

    NASA Astrophysics Data System (ADS)

    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 × M electrode contacts requires only N + M interconnects to a stimulator when active switching elements are used instead of N × 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.

  6. 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.

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

    PubMed Central

    Hirshler, Yafit (Kuttner); Polat, Uri; Biegon, Anat

    2009-01-01

    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 one week or eight weeks post implantation and processed for in vitro autoradiography with [3H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and two and eight weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at one week as well as eight weeks post implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance two and eight 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. PMID:20026042

  8. 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.

  9. DBS - an rlogin multiplexor and output logger for DA systems

    SciTech Connect

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

    1994-12-31

    DART Bootstrap Services (dbs) is the first component of run-control for the DART Data Acquisition system - the DA for the 96{prime} 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) logfiles (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.

  10. Effects of Deep Brain Stimulation and Medication on Strength, Bradykinesia, and Electromyographic Patterns of the Ankle Joint in Parkinson’s 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 Parkinson’s disease (PD) after they received surgically implanted high-frequency stimulating electrodes in the subthalamic nucleus (STN). The experiment studied ankle strength, movement velocity, and the associated electromyographic patterns in PD patients, six of whom had tremor at the ankle. The patients were studied off treatment, ON STN deep brain stimulation (DBS), on medication, and on medication plus STN DBS. Twelve matched control subjects were also examined. Medication alone and STN DBS alone increased patients’ ankle strength, ankle velocity, agonist muscle burst amplitude, and agonist burst duration, while reducing the number of agonist bursts during movement. These findings were similar for PD patients with and without tremor. The combination of medication plus STN DBS normalized maximal strength at the ankle joint, but ankle movement velocity and electromyographic patterns were not normalized. The findings are the first to demonstrate that STN DBS and medication increase strength and movement velocity at the ankle joint. PMID:16124011

  11. 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

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

    PubMed Central

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

    2016-01-01

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

  13. Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl

    PubMed Central

    Lee, Woong-Woo; Ehm, Gwanhee; Yang, Hui-Jun; Song, In Ho; Lim, Yong Hoon; Kim, Mi-Ryoung; Kim, Young Eun; Hwang, Jae Ha; Park, Hye Ran; Lee, Jae Min; Kim, Jin Wook; Kim, Han-Joon; Kim, Cheolyoung; Kim, Hee Chan; Park, Eunkyoung; Kim, In Young; Kim, Dong Gyu

    2016-01-01

    Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson’s disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up. PMID:27018855

  14. Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl.

    PubMed

    Lee, Woong-Woo; Ehm, Gwanhee; Yang, Hui-Jun; Song, In Ho; Lim, Yong Hoon; Kim, Mi-Ryoung; Kim, Young Eun; Hwang, Jae Ha; Park, Hye Ran; Lee, Jae Min; Kim, Jin Wook; Kim, Han-Joon; Kim, Cheolyoung; Kim, Hee Chan; Park, Eunkyoung; Kim, In Young; Kim, Dong Gyu; Jeon, Beomseok; Paek, Sun Ha

    2016-01-01

    Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson's disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up. PMID:27018855

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

    PubMed

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

    2012-07-01

    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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Multiple-input single-output closed-loop isometric force control using asynchronous intrafascicular multi-electrode stimulation.

    PubMed

    Frankel, Mitchell A; Dowden, Brett R; Mathews, V John; Normann, Richard A; Clark, Gregory A; Meek, Sanford G

    2011-06-01

    Although asynchronous intrafascicular multi-electrode stimulation (IFMS) can evoke fatigue-resistant muscle force, a priori determination of the necessary stimulation parameters for precise force production is not possible. This paper presents a proportionally-modulated, multiple-input single-output (MISO) controller that was designed and experimentally validated for real-time, closed-loop force-feedback control of asynchronous IFMS. Experiments were conducted on anesthetized felines with a Utah Slanted Electrode Array implanted in the sciatic nerve, either acutely or chronically ( n = 1 for each). Isometric forces were evoked in plantar-flexor muscles, and target forces consisted of up to 7 min of step, sinusoidal, and more complex time-varying trajectories. The controller was successful in evoking steps in force with time-to-peak of less than 0.45 s, steady-state ripple of less than 7% of the mean steady-state force, and near-zero steady-state error even in the presence of muscle fatigue, but with transient overshoot of near 20%. The controller was also successful in evoking target sinusoidal and complex time-varying force trajectories with amplitude error of less than 0.5 N and time delay of approximately 300 ms. This MISO control strategy can potentially be used to develop closed-loop asynchronous IFMS controllers for a wide variety of multi-electrode stimulation applications to restore lost motor function. PMID:21385670

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

    PubMed

    Makeyev, Oleksandr; Luna-Munguía, 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

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

    PubMed

    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 (I(DC)) and dorsal root fiber thresholds (I(DR)) at various anodal current ratios. I(DC) and I(DR) 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. PMID:21248383

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

  5. Assessment of a method to determine deep brain stimulation targets using deterministic tractography in a navigation system.

    PubMed

    Avecillas-Chasin, Josué M; Alonso-Frech, Fernando; Parras, Olga; Del Prado, Nayade; Barcia, Juan A

    2015-10-01

    Recent advances in imaging permit radiologic identification of target structures for deep brain stimulation (DBS) for movement disorders. However, these methods cannot detect the internal subdivision and thus cannot determine the appropriate DBS target located within those subdivisions. The aim of this study is to provide a straightforward method to obtain an optimized target (OT) within DBS target nuclei using a widely available navigation system. We used T1- and T2-weighted images, fluid-attenuated inversion recovery (FLAIR) sequence, and diffusion tensor imaging (DTI) of nine patients operated for DBS in our center. Using the StealthViz® software, we segmented the targeted deep structures (subcortical targets) and the anatomically identifiable areas to which these target nuclei were connected (projection areas). We generated fiber tracts from the projection areas. By identifying their intersections with the subcortical targets, we obtained an OT within the DBS target nuclei. We computed the distances from the clinically effective electrode contacts (CEEC) to the OT obtained by our method and the targets provided by the atlas. These distances were compared using a Wilcoxon signed-rank test, with p < 0.05 considered statistically significant. We were able to identify OT coincident with the motor part of the subthalamic nucleus and the ventral intermediate nucleus. We clinically tested the results and found that the CEEC were significantly more closely related to the OT than with the targets obtained by the atlas. Our present results show that this novel method permits optimization of the stimulation site within the internal subdivisions of target nuclei for DBS. PMID:25962557

  6. A mnemonic for Parkinson disease patients considering DBS: a tool to improve perceived outcome of surgery.

    PubMed

    Okun, Michael S; Foote, Kelly D

    2004-09-01

    Patients considering deep brain stimulation (DBS) for Parkinson disease (PD) may be exposed to videotapes, media coverage, or literature which show dramatic improvements in PD symptoms after surgical intervention. Based on this information, patients may seek a medical center with expertise in DBS for an evaluation and assessment of their candidacy for surgery. If patients receive a device, they may be disappointed or despondent following surgery because of a failure to achieve a preconceived and unrealistic outcome. In order to address the important issue of patient misconception of potential outcome, we have introduced a simple mnemonic device. The device may be taught and then reviewed with patients and families both before and after surgery. Use of this mnemonic device may allow the patient and family the time necessary to alter the perception of perceived benefit. This education can help to ensure that outcome meets or exceeds expectation, and as a result they become a more satisfied and easy-to-manage DBS patient. PMID:15335446

  7. 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, 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

  8. A novel technique for increasing charge injection capacity of neural electrodes for efficacious and safe neural stimulation.

    PubMed

    Negi, Sandeep; Bhandari, Rajmohan; Solzbacher, Florian

    2012-01-01

    Neural prostheses require chronically implanted small area penetrating electrode arrays that can stimulate and record neural activity. The fundamental requirement of neural electrodes is to have low interface impedance and large charge injection capacity (CIC). To achieve this fundamental requirement, we developed a novel technique to modify the surface of the Utah Electrode Array (UEA) to increase the real surface area without changing the geometrical surface area. Pt was coated on modified and unmodified (control) UEAs and electrochemical characterization such as impedance and CIC was measured and compared. The surface modified electrode impedance and CIC was ∼188 Ohm and ∼24 mC/cm(2) respectively. Increasing the real surface area of electrodes decreases the impedance by 1000 times and increases the CIC by 80 times compared to the control samples. The CIC of modified UEA was significantly higher than of any material reported in the literature, higher than sputtered iridium oxide (4 mC/cm(2)) or PEDOT (15 mC/cm(2)). PMID:23367086

  9. 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

  10. 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, 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

  11. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-13

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  15. 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.

  16. Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation.

    PubMed

    Lu, Hsiang-Chin; Chang, Wei-Jen; Chang, Wei-Pang; Shyu, Bai-Chuang

    2016-01-01

    Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the stimulation parameters (e.g., orientation, field strength, and stimulation duration) need to be examined in mice brain slice preparations. Testing and arranging the orientation of the electrode relative to the position of the mice brain slice are feasible. The present method preserves the thalamocingulate pathway to evaluate the effect of DCS on anterior cingulate cortex seizure-like activities. The results of the multichannel array recordings indicated that cathodal DCS significantly decreased the amplitude of the stimulation-evoked responses and duration of 4-aminopyridine and bicuculline-induced seizure-like activity. This study also found that cathodal DCS applications at 15 min caused long-term depression in the thalamocingulate pathway. The present study investigates the effects of DCS on thalamocingulate synaptic plasticity and acute seizure-like activities. The current procedure can test the optimal stimulation parameters including orientation, field strength, and stimulation duration in an in vitro mouse model. Also, the method can evaluate the effects of DCS on cortical seizure-like activities at both the cellular and network levels. PMID:27341682

  17. Lessons Learned from Open-label Deep Brain Stimulation for Tourette Syndrome: Eight Cases over 7 Years

    PubMed Central

    Motlagh, Maria G.; Smith, Megan E.; Landeros-Weisenberger, Angeli; Kobets, Andrew J.; King, Robert A.; Miravite, Joan; de Lotbinière, Alain C. J.; Alterman, Ron L.; Mogilner, Alon Y.; Pourfar, Michael H.; Okun, Michael S.; Leckman, James F.

    2013-01-01

    Background Deep brain stimulation (DBS) remains an experimental but promising treatment for patients with severe refractory Gilles de la Tourette syndrome (TS). Controversial issues include the selection of patients (age and clinical presentation), the choice of brain targets to obtain optimal patient-specific outcomes, and the risk of surgery- and stimulation-related serious adverse events. Methods This report describes our open-label experience with eight patients with severe refractory malignant TS treated with DBS. The electrodes were placed in the midline thalamic nuclei or globus pallidus, pars internus, or both. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video Protocol and the Yale Global Tic Severity Scale (YGTSS). Results Although three patients had marked postoperative improvement in their tics (>50% improvement on the YGTSS), the majority did not reach this level of clinical improvement. Two patients had to have their DBS leads removed (one because of postoperative infection and another because of lack of benefit). Discussion Our clinical experience supports the urgent need for more data and refinements in interventions and outcome measurements for severe, malignant, and medication-refractory TS. Because TS is not an etiologically homogenous clinical entity, the inclusion criteria for DBS patients and the choice of brain targets will require more refinement. PMID:24255802

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

    PubMed

    Dupré, Derrick A; Tomycz, Nestor; Oh, Michael Y; Whiting, Donald

    2015-06-01

    The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation--caloric intake and energy expenditure. PMID:26030707

  19. Stimulation through electrodes implanted near the subthalamic nucleus activates projections to motor areas of cerebral cortex in patients with Parkinson's disease.

    PubMed

    MacKinnon, Colum D; Webb, Ruth M; Silberstein, Paul; Tisch, Steven; Asselman, Peter; Limousin, Patricia; Rothwell, John C

    2005-03-01

    High-frequency electrical stimulation through electrodes implanted in the subthalamic nucleus (STN) has been shown to reduce significantly the cardinal symptoms of Parkinson's disease (PD). Despite the success of this treatment, the mechanisms of action of stimulation are poorly understood. To elucidate further the mechanisms of action of deep brain stimulation and its effects on cortical activity, we recorded electroencephalographic potentials from 61 scalp-surface electrodes during low-frequency (5-10 Hz) bipolar stimulation in 11 patients with advanced PD (14 implanted electrodes were tested). In all electrodes tested, stimulation through at least one of the four contacts produced a medium-latency waveform with an average onset of 14 +/- 3 ms and peak at 23 +/- 4 ms. This potential typically increased in magnitude across contacts from ventral to dorsal. Within-subject comparisons of median nerve somatosensory evoked potentials demonstrated that the generator of the medium-latency potential was within the primary sensorimotor cortex or lateral premotor cortex ipsilateral to stimulation. The timing and topography of this potential were consistent with indirect activation of the cortex by excitation of pallido-thalamic axons that traverse the dorsal aspect of the STN. The potential evoked by stimulation through the contact used for optimal clinical effect was highly variable across electrodes and frequently different from the medium-latency potential described above, suggesting that the neuronal elements mediating the medium-latency potential were different from those that mediate the clinical effects. PMID:15813949

  20. 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

  1. 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; Jakšić, Milko; Genovese, Marco; Olivero, Paolo

    2015-01-01

    Focused MeV ion beams with micrometric resolution are suitable tools for the direct writing of conductive graphitic channels buried in an insulating diamond bulk, as already demonstrated for different device applications. In this work we apply this fabrication method to the electrical excitation of color centers in diamond, demonstrating the potential of electrical stimulation in diamond-based single-photon sources. Differently from optically-stimulated light emission from color centers in diamond, electroluminescence (EL) requires a high current flowing in the diamond subgap states between the electrodes. With this purpose, buried graphitic electrode pairs, 10 μm spaced, were fabricated in the bulk of a single-crystal diamond sample using a 6 MeV C microbeam. The electrical characterization of the structure showed a significant current injection above an effective voltage threshold of 150 V, which enabled the stimulation of a stable EL emission. The EL imaging allowed to identify the electroluminescent regions and the residual vacancy distribution associated with the fabrication technique. Measurements evidenced isolated electroluminescent spots where non-classical light emission in the 560-700 nm spectral range was observed. The spectral and auto-correlation features of the EL emission were investigated to qualify the non-classical properties of the color centers. PMID:26510889

  2. Stump nerve signals during transcranial magnetic motor cortex stimulation recorded in an amputee via longitudinal intrafascicular electrodes.

    PubMed

    Rossini, P M; Rigosa, Jacopo; Micera, Silvestro; Assenza, Giovanni; Rossini, Luca; Ferreri, Florinda

    2011-04-01

    Do central and peripheral motor pathways associated with an amputated limb retain at least some functions over periods of years? This problem could be addressed by evaluating the response patterns of nerve signals from peripheral motor fibers during transcranial magnetic stimulation (TMS) of corticospinal tracts. The aim of this study was to record for the first time TMS-related responses from the nerves of a left arm stump of an amputee via intrafascicular longitudinal flexible multi-electrodes (tfLIFE4) implanted for a prosthetic hand control. After tfLIFE4 implant in the stump median and ulnar nerves, TMS impulses of increasing intensity were delivered to the contralateral motor cortex while tfLIFE4 recordings were carried out. Combining TMS of increasing intensity and tfLIFE4 electrodes recordings, motor nerve activity possibly related to the missing limb motor control and selectively triggered by brain stimulation without significant electromyographic contamination was identified. These findings are entirely original and indicate that tfLIFE4 signals are clearly driven from M1 stimulation, therefore witnessing the presence in the stump nerves of viable motor signals from the CNS possibly useful for artificial prosthesis control. PMID:21390489

  3. 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.

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

    PubMed Central

    Forneris, Jacopo; Traina, Paolo; Monticone, Daniele Gatto; Amato, Giampiero; Boarino, Luca; Brida, Giorgio; Degiovanni, Ivo P.; Enrico, Emanuele; Moreva, Ekaterina; Grilj, Veljko; Skukan, Natko; Jakšić, Milko; Genovese, Marco; Olivero, Paolo

    2015-01-01

    Focused MeV ion beams with micrometric resolution are suitable tools for the direct writing of conductive graphitic channels buried in an insulating diamond bulk, as already demonstrated for different device applications. In this work we apply this fabrication method to the electrical excitation of color centers in diamond, demonstrating the potential of electrical stimulation in diamond-based single-photon sources. Differently from optically-stimulated light emission from color centers in diamond, electroluminescence (EL) requires a high current flowing in the diamond subgap states between the electrodes. With this purpose, buried graphitic electrode pairs, 10 μm spaced, were fabricated in the bulk of a single-crystal diamond sample using a 6 MeV C microbeam. The electrical characterization of the structure showed a significant current injection above an effective voltage threshold of 150 V, which enabled the stimulation of a stable EL emission. The EL imaging allowed to identify the electroluminescent regions and the residual vacancy distribution associated with the fabrication technique. Measurements evidenced isolated electroluminescent spots where non-classical light emission in the 560–700 nm spectral range was observed. The spectral and auto-correlation features of the EL emission were investigated to qualify the non-classical properties of the color centers. PMID:26510889

  5. Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

    The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation

  6. Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications

    PubMed Central

    Xiao, YiZi; Zitella, Laura M.; Duchin, Yuval; Teplitzky, Benjamin A.; Kastl, Daniel; Adriany, Gregor; Yacoub, Essa; Harel, Noam; Johnson, Matthew D.

    2016-01-01

    Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS. PMID:27375422

  7. 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.

  8. Mechanism of Deep Brain Stimulation: Inhibition, Excitation, or Disruption?

    PubMed

    Chiken, Satomi; Nambu, Atsushi

    2016-06-01

    Deep brain stimulation (DBS), applying high-frequency electrical stimulation to deep brain structures, has now provided an effective therapeutic option for treatment of various neurological and psychiatric disorders. DBS targeting the internal segment of the globus pallidus, subthalamic nucleus, and thalamus is used to treat symptoms of movement disorders, such as Parkinson's disease, dystonia, and tremor. However, the mechanism underlying the beneficial effects of DBS remains poorly understood and is still under debate: Does DBS inhibit or excite local neuronal elements? In this short review, we would like to introduce our recent work on the physiological mechanism of DBS and propose an alternative explanation: DBS dissociates input and output signals, resulting in the disruption of abnormal information flow through the stimulation site. PMID:25888630

  9. Hindlimb Movement in the Cat Induced by Amplitude-Modulated Stimulation Using Extra-Spinal Electrodes

    PubMed Central

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

    2010-01-01

    Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of 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. PMID:18369283

  10. 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.

  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. Performance of DBS-Radio using concatenated coding and equalization

    NASA Technical Reports Server (NTRS)

    Gevargiz, J.; Bell, D.; Truong, L.; Vaisnys, A.; Suwitra, K.; Henson, P.

    1995-01-01

    The Direct Broadcast Satellite-Radio (DBS-R) receiver is being developed for operation in a multipath Rayleigh channel. This receiver uses equalization and concatenated coding, in addition to open loop and closed loop architectures for carrier demodulation and symbol synchronization. Performance test results of this receiver are presented in both AWGN and multipath Rayleigh channels. Simulation results show that the performance of the receiver operating in a multipath Rayleigh channel is significantly improved by using equalization. These results show that fractional-symbol equalization offers a performance advantage over full symbol equalization. Also presented is the base-line performance of the DBS-R receiver using concatenated coding and interleaving.

  13. Application of software simulation to DBS transmission design and evaluation

    NASA Astrophysics Data System (ADS)

    White, Lawrence W.; Palmer, Larry C.; Chang, Peter Y.; Shenoy, Ajit

    The paper describes software simulation results in the following three areas related to DBS planning: multipath and overdeviation of the video signal, digital audio transmission, and phase-locked loop demodulation. The results obtained for multipath and overdeviation involved simulation to examine a dual-path phenomenon that can be encountered in DBS applications. Results are also presented on the insertion of high rate digital data directly into the horizontal blanking interval of the video scan line. The results of simulations with a phase-locked demodular determined the degree of threshold extension achieved for various test patterns, as compared to a conventional limiter/discriminator.

  14. A novel ring electrode setup for the recording of somatosensory evoked potentials during transcranial direct current stimulation (tDCS).

    PubMed

    Sehm, Bernhard; Hoff, Maike; Gundlach, Christopher; Taubert, Marco; Conde, Virginia; Villringer, Arno; Ragert, Patrick

    2013-01-30

    Transcranial direct current stimulation (tDCS) modulates cortical excitability thereby influencing behavior and learning. While previous studies focused on tDCS after-effects, limited information about "online" tDCS effects is available. This in turn is an important prerequisite to better characterize and/or optimize tDCS effects. Here, we aimed to explore the feasibility of recording low-artifact somatosensory evoked potentials (SEPs) during tDCS using a novel ring electrode setup. We recorded SEP before, during and after 10 min of anodal or sham tDCS using a full-band direct current (DC) EEG system in a total number of 3 subjects. SEPs were recorded in the bore of the tDCS ring electrode. Using this approach, no tDCS-induced artifacts could be observed after the application of a standard EEG filter. This new setup might help to better characterize how tDCS alters evoked brain responses thus providing novel insight into underlying physiological effects during stimulation. PMID:23103376

  15. Deep Brain Stimulation

    PubMed Central

    Perlmutter, Joel S.; Mink, Jonathan W.

    2015-01-01

    Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics. PMID:16776585

  16. Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression

    PubMed Central

    Malone, Donald A.; Dougherty, Darin D.; Rezai, Ali R.; Carpenter, Linda L.; Friehs, Gerhard M.; Eskandar, Emad N.; Rauch, Scott L.; Rasmussen, Steven A.; Machado, Andre G.; Kubu, Cynthia S.; Tyrka, Audrey R.; Price, Lawrence H.; Stypulkowski, Paul H.; Giftakis, Jonathon E.; Rise, Mark T.; Malloy, Paul F.; Salloway, Stephen P.; Greenberg, Benjamin D.

    2012-01-01

    Background We investigated the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) for treatment refractory depression. Methods Fifteen patients with chronic, severe, highly refractory depression received open-label DBS at three collaborating clinical sites. Electrodes were implanted bilaterally in the VC/VS region. Stimulation was titrated to therapeutic benefit and the absence of adverse effects. All patients received continuous stimulation and were followed for a minimum of 6 months to longer than 4 years. Outcome measures included the Hamilton Depression Rating Scale—24 item (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Global Assessment of Function Scale (GAF). Results Significant improvements in depressive symptoms were observed during DBS treatment. Mean HDRS scores declined from 33.1 at baseline to 17.5 at 6 months and 14.3 at last follow-up. Similar improvements were seen with the MADRS (34.8, 17.9, and 15.7, respectively) and the GAF (43.4, 55.5, and 61.8, respectively). Responder rates with the HDRS were 40% at 6 months and 53.3% at last follow-up (MADRS: 46.7% and 53.3%, respectively). Remission rates were 20% at 6 months and 40% at last follow-up with the HDRS (MADRS: 26.6% and 33.3%, respectively). The DBS was well-tolerated in this group. Conclusions Deep brain stimulation of the VC/VS offers promise for the treatment of refractory major depression. PMID:18842257

  17. 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

  18. 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.

  19. 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…

  20. 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.

  1. 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, 100μs duration, 10mA biphasic current waveforms for 700 hours at 67°C 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

  2. Endovascular Electrodes for Electrical Stimulation of Blood Vessels for Vasoconstriction - a Finite Element Simulation Study.

    PubMed

    Kezurer, Noa; Farah, Nairouz; Mandel, Yossi

    2016-01-01

    Hemorrhagic shock accounts for 30-40 percent of trauma mortality, as bleeding may sometimes be hard to control. Application of short electrical pulses on blood vessels was recently shown to elicit robust vasoconstriction and reduction of blood loss following vascular injury. In this study we present a novel approach for vasoconstriction based on endovascular application of electrical pulses for situations where access to the vessel is limited. In addition to ease of access, we hypothesize that this novel approach will result in a localized and efficient vasoconstriction. Using computer modeling (COMSOL Multiphysics, Electric Currents Module), we studied the effect of endovascular pulsed electrical treatment on abdominal aorta of pigs, and compared the efficiency of different electrodes configurations on the electric field amplitude, homogeneity and locality when applied on a blood vessel wall. Results reveal that the optimal configuration is the endovascular approach where four electrodes are used, spaced 13 mm apart. Furthermore, computer based temperature investigations (bio-heat model, COMSOL Multiphysics) show that the maximum expected temperature rise is of 1.2 degrees; highlighting the safety of the four endovascular electrodes configuration. These results can aid in planning the application of endovascular pulsed electrical treatment as an efficient and safe vasoconstriction approach. PMID:27534438

  3. Endovascular Electrodes for Electrical Stimulation of Blood Vessels for Vasoconstriction – a Finite Element Simulation Study

    PubMed Central

    Kezurer, Noa; Farah, Nairouz; Mandel, Yossi

    2016-01-01

    Hemorrhagic shock accounts for 30–40 percent of trauma mortality, as bleeding may sometimes be hard to control. Application of short electrical pulses on blood vessels was recently shown to elicit robust vasoconstriction and reduction of blood loss following vascular injury. In this study we present a novel approach for vasoconstriction based on endovascular application of electrical pulses for situations where access to the vessel is limited. In addition to ease of access, we hypothesize that this novel approach will result in a localized and efficient vasoconstriction. Using computer modeling (COMSOL Multiphysics, Electric Currents Module), we studied the effect of endovascular pulsed electrical treatment on abdominal aorta of pigs, and compared the efficiency of different electrodes configurations on the electric field amplitude, homogeneity and locality when applied on a blood vessel wall. Results reveal that the optimal configuration is the endovascular approach where four electrodes are used, spaced 13 mm apart. Furthermore, computer based temperature investigations (bio-heat model, COMSOL Multiphysics) show that the maximum expected temperature rise is of 1.2 degrees; highlighting the safety of the four endovascular electrodes configuration. These results can aid in planning the application of endovascular pulsed electrical treatment as an efficient and safe vasoconstriction approach. PMID:27534438

  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

  5. 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

  6. 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

  7. 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

  8. Did My Brain Implant Make Me Do It? Questions Raised by DBS Regarding Psychological Continuity, Responsibility for Action and Mental Competence.

    PubMed

    Klaming, Laura; Haselager, Pim

    2013-01-01

    Deep brain stimulation (DBS) is a well-accepted treatment for movement disorders and is currently explored as a treatment option for various neurological and psychiatric disorders. Several case studies suggest that DBS may, in some patients, influence mental states critical to personality to such an extent that it affects an individual's personal identity, i.e. the experience of psychological continuity, of persisting through time as the same person. Without questioning the usefulness of DBS as a treatment option for various serious and treatment refractory conditions, the potential of disruptions of psychological continuity raises a number of ethical and legal questions. An important question is that of legal responsibility if DBS induced changes in a patient's personality result in damage caused by undesirable or even deviant behavior. Disruptions in psychological continuity can in some cases also have an effect on an individual's mental competence. This capacity is necessary in order to obtain informed consent to start, continue or stop treatment, and it is therefore not only important from an ethical point of view but also has legal consequences. Taking the existing literature and the Dutch legal system as a starting point, the present paper discusses the implications of DBS induced disruptions in psychological continuity for a patient's responsibility for action and competence of decision and raises a number of questions that need further research. PMID:24273622

  9. Reaching to proprioceptively defined targets in Parkinson's disease: effects of deep brain stimulation therapy.

    PubMed

    Lee, D; Henriques, D Y; Snider, J; Song, D; Poizner, H

    2013-08-01

    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 ganglia-cortical circuits are thought to be excessively noisy in patients with Parkinson's disease (PD), based in part on the lack of specificity of proprioceptive signals in basal ganglia-thalamic-cortical 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Spinal Anesthesia and Minimal Invasive Laminotomy for Paddle Electrode Placement in Spinal Cord Stimulation: Technical Report and Clinical Results at Long-Term Followup

    PubMed Central

    Sarubbo, S.; Latini, F.; Tugnoli, V.; Quatrale, R.; Granieri, E.; Cavallo, M. A.

    2012-01-01

    Object. We arranged a mini-invasive surgical approach for implantation of paddle electrodes for SCS under spinal anesthesia obtaining the best paddle electrode placement and minimizing patients' discomfort. We describe our technique supported by neurophysiological intraoperative monitoring and clinical results. Methods. 16 patients, affected by neuropathic pain underwent the implantation of paddle electrodes for spinal cord stimulation in lateral decubitus under spinal anesthesia. The paddle was introduced after flavectomy and each patient confirmed the correct distribution of paresthesias induced by intraoperative test stimulation. VAS and patients' satisfaction rate were recorded during the followup and compared to preoperative values. Results. No patients reported discomfort during the procedure. In all cases, paresthesias coverage of the total painful region was achieved, allowing the best final electrode positioning. At the last followup (mean 36.7 months), 87.5% of the implanted patients had a good rate of satisfaction with a mean VAS score improvement of 70.5%. Conclusions. Spinal cord stimulation under spinal anesthesia allows an optimal positioning of the paddle electrodes without any discomfort for patients or neurosurgeons. The best intraoperative positioning allows a better postoperative control of pain, avoiding the risk of blind placements of the paddle or further surgery for their replacement. PMID:22566761

  17. [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

  18. Therapeutic stimulation versus ablation.

    PubMed

    Hariz, Marwan I; Hariz, Gun-Marie

    2013-01-01

    The renaissance of functional stereotactic neurosurgery was pioneered in the mid 1980s by Laitinen's introduction of Leksell's posteroventral pallidotomy for Parkinson´s disease (PD). This ablative procedure experienced a worldwide spread in the 1990s, owing to its excellent effect on dyskinesias and other symptoms of post-l-dopa PD. Modern deep brain stimulation (DBS), pioneered by Benabid and Pollak in 1987 for the treatment of tremor, first became popular when it was applied to the subthalamic nucleus (STN) in the mid 1990s, where it demonstrated a striking effect on all cardinal symptoms of advanced PD, and permitted reduced dosages of medication. DBS, as a nondestructive, adaptable, and reversible procedure that is proving safe in bilateral surgery on basal ganglia, has great appeal to clinicians and patients alike, despite the fact that it is expensive, laborious, and relies on very strict patient selection criteria, especially for STN DBS. Psychiatric surgery has experienced the same phenomenon, with DBS supplanting completely stereotactic ablative procedures. This chapter discusses the pros and cons of ablation versus stimulation and investigates the reasons why DBS has overshadowed proven efficient ablative procedures such as pallidotomy for PD, and capsulotomy and cingulotomy for obsessive-compulsive disorder and depression. PMID:24112885

  19. Facilitating effects of deep brain stimulation on feedback learning in Parkinson's disease.

    PubMed

    Meissner, Sarah Nadine; Südmeyer, Martin; Keitel, Ariane; Pollok, Bettina; Bellebaum, Christian

    2016-10-15

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides an effective treatment for Parkinson's disease (PD) motor symptoms. However, findings of effects on cognitive function such as feedback learning remain controversial and rare. The aim of the present study was to gain a better understanding of cognitive alterations associated with STN-DBS. Therefore, we investigated effects of STN-DBS on active and observational feedback learning in PD. 18 PD patients with STN-DBS and 18 matched healthy controls completed active and observational feedback learning tasks. Patients were investigated ON and OFF STN-DBS. Tasks consisted of learning (with feedback) and test phases (without feedback). STN-DBS improved active learning during feedback trials and PD patients ON (but not OFF) STN-DBS showed comparable performance patterns as healthy controls. No STN-DBS effect was found when assessing performance during active test trials without feedback. In this case, however, STN-DBS effects were found to depend on symptom severity. While more impaired patients benefited from STN-DBS, stimulation had no facilitating effect on patients with less severe symptoms. Along similar lines, the severity of motor symptoms tended to be significantly correlated with differences in active test performance due to STN-DBS. For observational feedback learning, there was a tendency for a positive STN-DBS effect with patients reaching the performance level of healthy controls only ON STN-DBS. The present data suggest that STN-DBS facilitates active feedback learning in PD patients. Furthermore, they provide first evidence that STN-DBS might not only affect learning from own but also from observed actions and outcomes. PMID:27374161

  20. Invasive stimulation therapies for the treatment of refractory pain.

    PubMed

    Nizard, Julien; Raoul, Sylvie; Nguyen, Jean-Paul; Lefaucheur, Jean-Pascal

    2012-10-01

    Invasive neurostimulation therapies may be proposed to patients with neuropathic pain refractory to conventional medical management, in order to improve pain relief, functional capacity, and quality of life. In this review, the respective mechanisms of action and efficacy of peripheral nerve stimulation (PNS), nerve root stimulation (NRS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and motor cortex stimulation (MCS) are discussed. PNS appears to be useful in various refractory neuropathic pain indications (as long as there is some preservation of sensation in the painful area), such as intractable chronic headache, pelvic and perineal pain, and low back pain, but evidence for its efficacy is not strongly conclusive, and large-scale randomized controlled studies are necessary to confirm the efficacy in the long term. Spinal cord stimulation (SCS) has been validated for the treatment of selected types of chronic pain syndromes, such as Failed Back Surgery Syndrome, and Complex Regional Pain Syndrome type I. When neuropathic pain is secondary to a brain lesion (especially following stroke) or a trigeminal lesion, stimulation of brain structures is required. Deep brain stimulation (DBS), which can be proposed with targets like the periventricular/periaqueductal gray matter or the sensory thalamus, is increasingly replaced by motor cortex stimulation (MCS), mainly because it is safer, more easily performed, and probably more effective in a wider range of indications (including central post-stroke pain). The respective places of DBS and MCS in some selected indications, such as peripheral neuropathic pain and phantom limb pain, have yet to be clearly delineated. Controlled trials, with the stimulator switched ON or OFF in a double-blind procedure, have demonstrated the efficacy of MCS in the treatment of peripheral and central neuropathic pain, although these trials included a limited number of patients and need to be confirmed by large, controlled

  1. The Use of Deep Brain Stimulation in Tourette Syndrome.

    PubMed

    Akbarian-Tefaghi, Ladan; Zrinzo, Ludvic; Foltynie, Thomas

    2016-01-01

    Tourette syndrome (TS) is a childhood neurobehavioural disorder, characterised by the presence of motor and vocal tics, typically starting in childhood but persisting in around 20% of patients into adulthood. In those patients who do not respond to pharmacological or behavioural therapy, deep brain stimulation (DBS) may be a suitable option for potential symptom improvement. This manuscript attempts to summarise the outcomes of DBS at different targets, explore the possible mechanisms of action of DBS in TS, as well as the potential of adaptive DBS. There will also be a focus on the future challenges faced in designing optimized trials. PMID:27548235

  2. 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

  3. Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Unipolar and Bipolar Depression

    PubMed Central

    Holtzheimer, Paul E.; Kelley, Mary E.; Gross, Robert E.; Filkowski, Megan M.; Garlow, Steven J.; Barrocas, Andrea; Wint, Dylan; Craighead, Margaret C.; Kozarsky, Julie; Chismar, Ronald; Moreines, Jared L.; Mewes, Klaus; Posse, Patricio Riva; Gutman, David A.; Mayberg, Helen S.

    2015-01-01

    Context Deep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited. Objective To assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar II disorder (BP). Design Open-label trial with a sham lead-in phase. Setting Academic medical center. Patients Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation. Main Outcome Measures Change in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation. Results A significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n=17), 5 (36%) and 5 (36%) after 1 year (n=14), and 7 (58%) and 11 (92%) after 2 years (n=12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase

  4. Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson's Disease.

    PubMed

    Nassery, Adam; Palmese, Christina A; Sarva, Harini; Groves, Mark; Miravite, Joan; Kopell, Brian Harris

    2016-10-01

    Deep brain stimulation (DBS) is effective for Parkinson's disease (PD), dystonia, and essential tremor (ET). While motor benefits are well documented, cognitive and psychiatric side effects from the subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS for PD are increasingly recognized. Underlying disease, medications, microlesions, and post-surgical stimulation likely all contribute to non-motor symptoms (NMS). PMID:27539167

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease.

    PubMed

    Tremblay, Christina; Macoir, Joël; Langlois, Mélanie; Cantin, Léo; Prud'homme, Michel; Monetta, Laura

    2015-02-01

    The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) on different language abilities are still controversial and its impact on high-level language abilities such as metaphor comprehension has been overlooked. The aim of this study was to determine the effects of STN electrical stimulation on metaphor comprehension and language abilities such as lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on metaphor comprehension, lexical decision, word association and verbal fluency tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN stimulation had a significant beneficial effect on motor symptoms in PD. However, this stimulation did not have any effect on metaphor comprehension or any other cognitive ability evaluated in this study. These outcomes suggest that STN stimulation may have dissociable effects on motor and language functions. PMID:25577507

  10. The adaptive deep brain stimulation challenge.

    PubMed

    Arlotti, Mattia; Rosa, Manuela; Marceglia, Sara; Barbieri, Sergio; Priori, Alberto

    2016-07-01

    Sub-optimal clinical outcomes of conventional deep brain stimulation (cDBS) in treating Parkinson's Disease (PD) have boosted the development of new solutions to improve DBS therapy. Adaptive DBS (aDBS), consisting of closed-loop, real-time changing of stimulation parameters according to the patient's clinical state, promises to achieve this goal and is attracting increasing interest in overcoming all of the challenges posed by its development and adoption. In the design, implementation, and application of aDBS, the choice of the control variable and of the control algorithm represents the core challenge. The proposed approaches, in fact, differ in the choice of the control variable and control policy, in the system design and its technological limits, in the patient's target symptom, and in the surgical procedure needed. Here, we review the current proposals for aDBS systems, focusing on the choice of the control variable and its advantages and drawbacks, thus providing a general overview of the possible pathways for the clinical translation of aDBS with its benefits, limitations and unsolved issues. PMID:27079257

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

    PubMed Central

    Kent, Alexander R; Grill, Warren M

    2013-01-01

    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 10 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

  12. 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

  13. Electrical engram: how deep brain stimulation affects memory.

    PubMed

    Lee, Hweeling; Fell, Jürgen; Axmacher, Nikolai

    2013-11-01

    Deep brain stimulation (DBS) is a surgical procedure involving implantation of a pacemaker that sends electric impulses to specific brain regions. DBS has been applied in patients with Parkinson's disease, depression, and obsessive-compulsive disorder (among others), and more recently in patients with Alzheimer's disease to improve memory functions. Current DBS approaches are based on the concept that high-frequency stimulation inhibits or excites specific brain regions. However, because DBS entails the application of repetitive electrical stimuli, it primarily exerts an effect on extracellular field-potential oscillations similar to those recorded with electroencephalography. Here, we suggest a new perspective on how DBS may ameliorate memory dysfunction: it may enhance normal electrophysiological patterns underlying long-term memory processes within the medial temporal lobe. PMID:24126128

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

    PubMed

    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

  15. 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

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

    PubMed Central

    Miranda, Maisa F.; Hamani, Clement; de Almeida, Antônio-Carlos G.; Amorim, Beatriz O.; Macedo, Carlos E.; Fernandes, Maria José S.; Nobrega, José N.; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Andersen, Monica L.; Tufik, Sergio; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine. PMID:25324724

  17. Temporary deep brain stimulation in Gilles de la Tourette syndrome: A feasible approach?

    PubMed Central

    Zekaj, Edvin; Saleh, Christian; Porta, Mauro; Servello, Domenico

    2015-01-01

    Background: Gilles de la Tourette Syndrome (GTS) is a complex neuropsychiatric disorder, characterized by chronic motor and vocal tics, associated in 50–90% of cases with psychiatric comorbidities. Patients with moderate and severe clinical picture are treated with psychotherapy and pharmacological therapy. Deep brain stimulation (DBS) is reserved for pharmacological refractory GTS patients. As GTS tends to improve with time and potentially resolves in the second decade of life, the major concern of DBS in GTS is the age at which the patient undergoes surgical procedure. Some authors suggest performing DBS after 18 years, others after 25 years of age. Case Description: We present a 25-year-old patient with GTS, who was aged 17 years and was treated with thalamic DBS. DBS resulted in progressive and sustained improvement of tics and co-morbidities. After 6 years of DBS treatment, it was noted that the clinical improvement was maintained also in OFF stimulation setting, so it was decided to keep it off. After 2 years in off-setting and stable clinical picture the entire DBS device was removed. Six months after DBS device removal the patient remained symptom-free. Conclusions: DBS is a therapeutic option reserved for severe and refractory GTS cases. In our opinion DBS might be considered as a temporary application in GTS. PMID:26290773

  18. High frequency stimulation abolishes thalamic network oscillations: an electrophysiological and computational analysis

    NASA Astrophysics Data System (ADS)

    Lee, Kendall H.; Hitti, Frederick L.; Chang, Su-Youne; Lee, Dongchul C.; Roberts, David W.; McIntyre, Cameron C.; Leiter, James C.

    2011-08-01

    Deep brain stimulation (DBS) of the thalamus has been demonstrated to be effective for the treatment of epilepsy. To investigate the mechanism of action of thalamic DBS, we examined the effects of high frequency stimulation (HFS) on spindle oscillations in thalamic brain slices from ferrets. We recorded intracellular and extracellular electrophysiological activity in the nucleus reticularis thalami (nRt) and in thalamocortical relay (TC) neurons in the lateral geniculate nucleus, stimulated the slice using a concentric bipolar electrode, and recorded the level of glutamate within the slice. HFS (100 Hz) of TC neurons generated excitatory post-synaptic potentials, increased the number of action potentials in both TC and nRt neurons, reduced the input resistance, increased the extracellular glutamate concentration, and abolished spindle wave oscillations. HFS of the nRt also suppressed spindle oscillations. In both locations, HFS was associated with significant and persistent elevation in extracellular glutamate levels and suppressed spindle oscillations for many seconds after the cessation of stimulation. We simulated HFS within a computational model of the thalamic network, and HFS also disrupted spindle wave activity, but the suppression of spindle activity was short-lived. Simulated HFS disrupted spindle activity for prolonged periods of time only after glutamate release and glutamate-mediated activation of a hyperpolarization-activated current (Ih) was incorporated into the model. Our results suggest that the mechanism of action of thalamic DBS as used in epilepsy may involve the prolonged release of glutamate, which in turn modulates specific ion channels such as Ih, decreases neuronal input resistance, and abolishes thalamic network oscillatory activity.

  19. 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.

  20. 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

  1. 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

  2. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    PubMed

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life. PMID:20885119

  3. 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

  4. 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

  5. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens.

    PubMed

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

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  6. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    PubMed Central

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

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  7. Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats.

    PubMed

    Sutton, Alexander C; O'Connor, Katherine A; Pilitsis, Julie G; Shin, Damian S

    2015-11-01

    Deep brain stimulation (DBS) is effective in managing motor symptoms of Parkinson's disease in well-selected individuals. Recently, research has shown that DBS in the basal ganglia (BG) can alter neural circuits beyond the traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance, functional imaging showed alterations in cerebellar activity with DBS in the subthalamic nucleus (STN). However, these imaging studies revealed very little about how cell-specific cerebellar activity responds to STN stimulation or if these changes contribute to its efficacy. In this study, we assess whether STN-DBS provides efficacy in managing motor symptoms in Parkinson's disease by recruiting cerebellar activity. We do this by applying STN-DBS in hemiparkinsonian rats and simultaneously recording neuronal activity from the STN, brainstem and cerebellum. We found that STN neurons decreased spiking activity by 55% during DBS (P = 0.038), which coincided with a decrease in most pedunculopontine tegmental nucleus and Purkinje neurons by 29% (P < 0.001) and 28% (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar nuclei increased 45% during DBS (P < 0.001), which was likely from reduced afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic current along with stimulation of the deep cerebellar nuclei and found similar improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests that STN-DBS can engage cerebellar activity to improve parkinsonian motor symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease alters cerebellar activity using electrophysiology in vivo and reveal a potential for stimulating the cerebellum to potentiate deep brain stimulation of the subthalamic nucleus. PMID:25124274

  8. 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

  9. Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study.

    PubMed

    Alonso, Fabiola; Latorre, Malcolm A; Göransson, Nathanael; Zsigmond, Peter; Wårdell, Karin

    2016-01-01

    New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a "virtual" ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode. PMID:27618109

  10. 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.

  11. 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

  12. 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.

  13. Ethical considerations in deep brain stimulation for psychiatric illness.

    PubMed

    Grant, Ryan A; Halpern, Casey H; Baltuch, Gordon H; O'Reardon, John P; Caplan, Arthur

    2014-01-01

    Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation. PMID:24055023

  14. Network Perspectives on the Mechanisms of Deep Brain Stimulation

    PubMed Central

    McIntyre, Cameron C.; Hahn, Philip J.

    2009-01-01

    Deep brain stimulation (DBS) is an established medical therapy for the treatment of movement disorders and shows great promise for several other neurological disorders. However, after decades of clinical utility the underlying therapeutic mechanisms remain undefined. Early attempts to explain the mechanisms of DBS focused on hypotheses that mimicked an ablative lesion to the stimulated brain region. More recent scientific efforts have explored the wide-spread changes in neural activity generated throughout the stimulated brain network. In turn, new theories on the mechanisms of DBS have taken a systems-level approach to begin to decipher the network activity. This review provides an introduction to some of the network based theories on the function and pathophysiology of the cortico-basal-ganglia-thalamo-cortical loops commonly targeted by DBS. We then analyze some recent results on the effects of DBS on these networks, with a focus on subthalamic DBS for the treatment of Parkinson's disease. Finally we attempt to summarize how DBS could be achieving its therapeutic effects by overriding pathological network activity. PMID:19804831

  15. Myoelectric stimulation on peroneal muscles with electrodes of the muscle belly size attached to the upper shank gives the best effect in resisting simulated ankle sprain motion.

    PubMed

    Fong, Daniel Tik-Pui; Wang, Dan; Chu, Vikki Wing-Shan; Chan, Kai-Ming

    2013-04-01

    Ankle sprain is a common sports related injury that may be caused by incorrect positioning of the foot prior to and at initial contact during landing from a jump or gait. Furthermore a delayed reaction of the peroneal muscle may also contribute to the injury mechanism. A recent study demonstrated that myoelectric stimulation of the peroneal muscles within 15 ms of a simulated inversion event would significantly resist an ankle spraining motion. This study further investigated its effect with three different electrode sizes and three different lateral shank attachment positions. Twelve male subjects with healthy ankles performed simulated ankle supination spraining motion on a pair of mechanical sprain simulators. A pair of electrodes of one of the three sizes (large, medium, small) was attached to one of the three positions (upper 1/4, middle, lower 1/4) along the lateral shank to deliver an electrical signal of 130 V for 0.5s when the sprain simulator started. Ankle kinematics data were collected by a tri-axial gyroscope motion sensor and the peak inward heel tilting velocity was obtained to represent the effect in resisting the simulated ankle spraining motion. Repeated measures one-way analysis of variance was performed and showed a significant drop from 273.3 (control, no stimulation) to 215.8 deg/s (21%) when small electrodes were attached to the upper 1/4 position. Decrease was found in all other conditions but the drops (11-18%) were not statistically significant. The small electrodes used in this study fitted the width of the peroneal muscle belly at the upper 1/4 position, so the electrical current may have well flowed to the motor points of the muscles to initiate quick contraction. PMID:23453396

  16. Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

    PubMed

    Heldmann, Marcus; Berding, Georg; Voges, Jürgen; Bogerts, Bernhard; Galazky, Imke; Müller, Ulf; Baillot, Gunther; Heinze, Hans-Jochen; Münte, Thomas F

    2012-01-01

    The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control. PMID:22629317

  17. Deep‐brain stimulation: long‐term analysis of complications caused by hardware and surgery—experiences from a single centre

    PubMed Central

    Voges, J; Waerzeggers, Y; Maarouf, M; Lehrke, R; Koulousakis, A; Lenartz, D; Sturm, V

    2006-01-01

    Objective To determine the surgery‐related and hardware‐related complications of deep‐brain stimulation (DBS) at a single centre. Methods 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long‐term complications (352 electrodes, mean follow‐up 36.3 (SD 20.8) months). Results The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long‐term observation period, hardware‐related problems were registered in 25 of 180 (13.9%) patients. Conclusions Stereotactic implantation of electrodes for DBS, if performed with multiplanar three‐dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients' prolonged hospital stay and repeated surgery were wound infections and hardware‐related complications. PMID:16574733

  18. Update on Deep Brain Stimulation for Dyskinesia and Dystonia: A Literature Review

    PubMed Central

    TODA, Hiroki; SAIKI, Hidemoto; NISHIDA, Namiko; IWASAKI, Koichi

    2016-01-01

    Deep brain stimulation (DBS) has been an established surgical treatment option for dyskinesia from Parkinson disease and for dystonia. The present article deals with the timing of surgical intervention, selecting an appropriate target, and minimizing adverse effects. We provide an overview of current evidences and issues for dyskinesia and dystonia as well as emerging DBS technology. PMID:27053331

  19. 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…

  20. Update on Deep Brain Stimulation for Dyskinesia and Dystonia: A Literature Review.

    PubMed

    Toda, Hiroki; Saiki, Hidemoto; Nishida, Namiko; Iwasaki, Koichi

    2016-05-15

    Deep brain stimulation (DBS) has been an established surgical treatment option for dyskinesia from Parkinson disease and for dystonia. The present article deals with the timing of surgical intervention, selecting an appropriate target, and minimizing adverse effects. We provide an overview of current evidences and issues for dyskinesia and dystonia as well as emerging DBS technology. PMID:27053331

  1. 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…

  2. The rationale for deep brain stimulation in Alzheimer's disease.

    PubMed

    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials. PMID:26443701

  3. DBS television systems under development in the United States of America

    NASA Astrophysics Data System (ADS)

    Clark, J. F.

    1985-01-01

    DBS system technology tradeoffs which were being considered as of October 1984 are reviewed. The economic goal is to provide acceptable image and programming quality at costs lower than those of CATV systems. Although receiver dish antenna costs are incurred by the DBS user, the satellite link avoids the capital intensive cable infrastructure. The DBS antennas may cause legal difficulties as DBS subscribers receive CATV regional unscrambled feeder signals. DBS service at 11 GHz has already begun in the NE U.S. with the Anik C2 satellite, which provides a 10 dB clear sky carrier/noise (C/N) ratio signal. Transponders on a Comsat DBS system (in advanced development) will employ vertically polarized signals to attain C/N ratios over 17 dB in concert with 75 cm home terminal antennas. The FCC has ruled that all DBS equipment shall have sufficient commonality at the receiving end so that a customer will need only to replace a baseband processor unit to change sources.

  4. Network effects of deep brain stimulation.

    PubMed

    Alhourani, Ahmad; McDowell, Michael M; Randazzo, Michael J; Wozny, Thomas A; Kondylis, Efstathios D; Lipski, Witold J; Beck, Sarah; Karp, Jordan F; Ghuman, Avniel S; Richardson, R Mark

    2015-10-01

    The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

  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. [MRI compatibility of deep brain stimulator].

    PubMed

    Zhang, Yujing

    2013-07-01

    Deep brain stimulation (DBS) therapy develops rapidly in clinical application. The structures of deep brain stimulator and magnetic resonance imaging (MRI) equipment are introduced, the interactions are analyzed, and the two compatible problems of radio frequency (RF) heating and imaging artifact are summarized in this paper. PMID:24195387

  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 study’s aim was to assess the safety and possible effects on affect and working memory of tDCS using two anodes for bifrontal stimulation. A group of healthy subjects participated in two bifrontal tDCS sessions on two different days, one for real and the other for sham stimulation. They performed a working memory task and reported their affect immediately before and after each tDCS session. Relative to sham, real bifrontal stimulation did not induce significant adverse effects, reduced decrement in vigor-activity during the study session, and did not improve working memory. These preliminary findings suggest that bifrontal anodal stimulation is feasible and safe and may reduce task-related fatigue in healthy participants. Its effects on neuropsychiatric patients deserve further study. PMID:26339204

  9. External trial deep brain stimulation device for the application of desynchronizing stimulation techniques

    NASA Astrophysics Data System (ADS)

    Hauptmann, C.; Roulet, J.-C.; Niederhauser, J. J.; Döll, W.; Kirlangic, M. E.; Lysyansky, B.; Krachkovskyi, V.; Bhatti, M. A.; Barnikol, U. B.; Sasse, L.; Bührle, C. P.; Speckmann, E.-J.; Götz, M.; Sturm, V.; Freund, H.-J.; Schnell, U.; Tass, P. A.

    2009-12-01

    In the past decade deep brain stimulation (DBS)—the application of electrical stimulation to specific target structures via implanted depth electrodes—has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

  10. Controlled on-chip stimulation of quantal catecholamine release from chromaffin cells using photolysis of caged Ca2+ on transparent indium-tin-oxide microchip electrodes.

    PubMed

    Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D

    2008-01-01

    Photorelease of caged Ca(2+) is a uniquely powerful tool to study the dynamics of Ca(2+)-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca(2+), together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm thick transparent indium-tin-oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (approximately 20 microm by 20 microm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca(2+) cage NP-EGTA and Ca(2+) indicator dye fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca(2+), a uniform rise of [Ca(2+)](i) within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca(2+)](i) and a "priming" effect of sub-stimulatory [Ca(2+)](i) on the response of cells to subsequent [Ca(2+)](i) elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca(2+) is a suitable stimulation technique for higher-throughput studies of Ca(2+)-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

  11. Controlled On-chip Stimulation of Quantal Catecholamine Release from Chromaffin Cells Using Photolysis of Caged Ca2+ on Transparent Indium-Tin-Oxide Microchip Electrodes

    PubMed Central

    Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D.

    2008-01-01

    Photorelease of caged Ca2+ is a uniquely powerful tool to study the dynamics of Ca2+-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca2+ together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm - thick transparent Indium-Tin-Oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (∼20 μm by 20 μm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca2+ cage NP-EGTA and Ca2+ indicator dye Fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca2+, a uniform rise of [Ca2+]i within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca2+]i and a “priming” effect of sub-stimulatory [Ca2+]i on the response of cells to subsequent [Ca2+]i elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca2+ is a suitable stimulation technique for higher-throughput studies of Ca2+-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

  12. No Impact of Deep Brain Stimulation on Fear-Potentiated Startle in Obsessive–Compulsive 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 obsessive–compulsive 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 obsessive–compulsive 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

  13. No impact of deep brain stimulation on fear-potentiated startle in obsessive-compulsive disorder.

    PubMed

    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 obsessive-compulsive 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 obsessive-compulsive 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

  14. 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

  15. Time and Frequency-Dependent Modulation of Local Field Potential Synchronization by Deep Brain Stimulation

    PubMed Central

    McCracken, Clinton B.; Kiss, Zelma H. T.

    2014-01-01

    High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS), is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP), the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson’s disease (PD). We performed simultaneous multi-site local field potential (LFP) recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective), low-frequency (LF, 15 Hz; ineffective) and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR), ventroanterior thalamus (VA), primary motor cortex (M1), and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic effects

  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

  17. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    PubMed Central

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G. P.; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J.; la Fleur, Susanne E.

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  18. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats.

    PubMed

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G P; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J; la Fleur, Susanne E

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  19. Neuropsychiatric deep brain stimulation for translational neuroimaging.

    PubMed

    Höflich, Anna; Savli, Markus; Comasco, Erika; Moser, Ulrike; Novak, Klaus; Kasper, Siegfried; Lanzenberger, Rupert

    2013-10-01

    From a neuroimaging point of view, deep brain stimulation (DBS) in psychiatric disorders represents a unique source of information to probe results gained in functional, structural and molecular neuroimaging studies in vivo. However, the implementation has, up to now, been restricted by the heterogeneity of the data reported in DBS studies. The aim of the present study was therefore to provide a comprehensive and standardized database of currently used DBS targets in selected psychiatric disorders (obsessive-compulsive disorder (OCD), treatment-resistant depression (TRD), Gilles de la Tourette syndrome (GTS)) to enable topological comparisons between neuroimaging results and stimulation areas. A systematic literature research was performed and all peer-reviewed publications until the year 2012 were included. Literature research yielded a total of 84 peer-reviewed studies including about 296 psychiatric patients. The individual stimulation data of 37 of these studies meeting the inclusion criteria which included a total of 202 patients (63 OCD, 89 TRD, 50 GTS) was translated into MNI stereotactic space with respect to AC origin in order to identify key targets. The created database can be used to compare DBS target areas in MNI stereotactic coordinates with: 1) activation patterns in functional brain imaging (fMRI, phfMRI, PET, MET, EEG); 2) brain connectivity data (e.g., MR-based DTI/tractography, functional and effective connectivity); 3) quantitative molecular distribution data (e.g., neuroreceptor PET, post-mortem neuroreceptor mapping); 4) structural data (e.g., VBM for neuroplastic changes). Vice versa, the structural, functional and molecular data may provide a rationale to define new DBS targets and adjust/fine-tune currently used targets in DBS based on this overview in stereotactic coordinates. Furthermore, the availability of DBS data in stereotactic space may facilitate the investigation and interpretation of treatment effects and side effect of DBS by

  20. Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

    PubMed

    Rossi, P Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J; Elias, W Jeff; Rossi, Marvin A; Butson, Christopher L; Fox, Michael D; McIntyre, Cameron C; Pouratian, Nader; Swann, Nicole C; de Hemptinne, Coralie; Gross, Robert E; Chizeck, Howard J; Tagliati, Michele; Lozano, Andres M; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L; Akbar, Umer; Gerhardt, Greg A; Grill, Warren M; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H; Lang, Anthony E; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y; Molina, Rene; Opri, Enrico; Otto, Kevin J; Oweiss, Karim G; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A; Shih, Ludy C; Steinke, G Karl; Tröster, Alexander I; Vanegas, Nora; Zaghloul, Kareem A; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D; Okun, Michael S

    2016-01-01

    The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies. PMID:27092042

  1. Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

    PubMed Central

    Rossi, P. Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J.; Elias, W. Jeff; Rossi, Marvin A.; Butson, Christopher L.; Fox, Michael D.; McIntyre, Cameron C.; Pouratian, Nader; Swann, Nicole C.; de Hemptinne, Coralie; Gross, Robert E.; Chizeck, Howard J.; Tagliati, Michele; Lozano, Andres M.; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L.; Akbar, Umer; Gerhardt, Greg A.; Grill, Warren M.; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H.; Lang, Anthony E.; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y.; Molina, Rene; Opri, Enrico; Otto, Kevin J.; Oweiss, Karim G.; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A.; Shih, Ludy C.; Steinke, G. Karl; Tröster, Alexander I.; Vanegas, Nora; Zaghloul, Kareem A.; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D.; Okun, Michael S.

    2016-01-01

    The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies. PMID:27092042

  2. Treatment of Wilson's disease motor complications with deep brain stimulation.

    PubMed

    Hedera, Peter

    2014-05-01

    A considerable proportion of patients with Wilson's disease (WD) experience neurologic symptoms that are functionally disabling. The most common neurologic problems in advanced WD include dystonia and tremor. Medically refractory idiopathic dystonia and essential tremor (ET) have been successfully treated with deep brain stimulation (DBS), functional surgical therapy targeting the globus pallidus pars interna (GPi), or the ventral intermediate (Vim) thalamic nucleus. Even though the pathophysiology of tremor is different in WD and ET, available experience supports DBS targeting the Vim for WD patients. Dystonia associated with WD is classified as secondary dystonia and GPi stimulation has yielded mixed results in these patients. The presence of structural changes in the basal ganglia may limit the therapeutic success of DBS for WD dystonia compared with idiopathic dystonia. In spite of these limitations, DBS in WD may be an effective approach to treat medically refractory residual neurologic symptoms in carefully selected patients. PMID:24547944

  3. Drowning hazard with deep brain stimulation: case report.

    PubMed

    Bangash, Omar K; Thorburn, Megan; Garcia-Vega, Jimena; Walters, Susan; Stell, Rick; Starkstein, Sergio E; Lind, Christopher R P

    2016-05-01

    The caudal zona incerta target within the posterior subthalamic area is an investigational site for deep brain stimulation (DBS) in Parkinson disease (PD) and tremor. The authors report on a patient with tremor-predominant PD who, despite excellent tremor control and an otherwise normal neurological examination, exhibited profound difficulty swimming during stimulation. Over the last 20 years, anecdotal reports have been received of 3 other patients with PD who underwent thalamic or pallidal lesioning or DBS surgery performed at the authors' center and subsequently drowned. It may be that DBS puts patients at risk for drowning by specifically impairing their ability to swim. Until this finding can be further examined in larger cohorts, patients should be warned to swim under close supervision soon after DBS surgery. PMID:26566200

  4. 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

  5. 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

  6. Brain Stimulation for Torsion Dystonia

    PubMed Central

    Fox, Michael D.; Alterman, Ron L.

    2016-01-01

    Dystonia is a heterogeneous neurological disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly utilized. Here we review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation. Strong (level B) evidence supports the use of deep brain stimulation (DBS) for the treatment of primary generalized or segmental dystonia, especially DYT-1, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer’s cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson’s disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques including epidural cortical stimulation and noninvasive brain stimulation have been investigated, but generally report smaller effect sizes in a more limited number of patients. Recent advances relevant to patient selection, surgical approach, DBS programming, and mechanism of action are discussed. PMID:25894231

  7. 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 Parkinson’s 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

  8. 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…

  9. Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease

    PubMed Central

    Wang, Xiao-Hong; Zhang, Lin; Sperry, Laura; Olichney, John; Farias, Sarah Tomaszewski; Shahlaie, Kiarash; Chang, Norika Malhado; Liu, Ying; Wang, Su-Ping; Wang, Cui

    2015-01-01

    Objective: This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD). Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus. Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients. PMID:26668154

  10. 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

  11. Validation of the Use of Dried Blood Spot (DBS) Method to Assess Vitamin A Status

    PubMed Central

    Fallah, Elham; Peighambardoust, Seyed Hadi

    2012-01-01

    Background: Vitamin A deficiency is an important dietary deficiency in the world. Thus, the ne¬cessity of screening for deficient populations is obvious. This paper introduces a fast, cheap and relatively reliable method called “dried blood spot” (DBS) method in screening the deficient populations. The validity of this method for retinol measurement was investigated. Method: The “precision” and “agreement” criteria of the DBS method were assessed. The preci¬sion was calculated and compared with those of plasma using F-test. The agreement was eva¬luated using Bland-Altman plot. Results: The imprecision of retinol measurements in dried spots was not significantly different from those of the control (plasma). A good correlation coefficient (r2=0.78) was obtained for dried spots’ retinol measurements versus plasma’s retinol analysis (P < 0.01). Paired t-test showed no significant difference between the DBS and retinol methods on a group level. Imprecision of DBS measurement was acceptable, compared to that of the plasma method. The difference be¬tween these two methods was not statistically significant on a group level. Conclusion: Application of DBS standard samples, in which a part of the plasma was replaced with the artificial plasma, was shown to be a reliable calibration mean for retinol measurements in DBS samples. Retinol in dried spots was stable for 90 days. Overall, the DBS method provided a precise measurement of retinol, showing results that were comparable with the measurement of retinol in plasma. PMID:24688932

  12. Deep Brain Stimulation for Obesity

    PubMed Central

    Sussman, Eric S; Zhang, Michael; Pendharkar, Arjun V; Azagury, Dan E; Bohon, Cara; Halpern, Casey H

    2015-01-01

    Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer’s disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain. PMID:26180683

  13. Intraoperative MRI for deep brain stimulation lead placement in Parkinson's disease: 1 year motor and neuropsychological outcomes.

    PubMed

    Sidiropoulos, Christos; Rammo, Richard; Merker, Brad; Mahajan, Abhimanyu; LeWitt, Peter; Kaminski, Patricia; Womble, Melissa; Zec, Adrianna; Taylor, Danette; Wall, Julia; Schwalb, Jason M

    2016-06-01

    Traditional deep brain stimulation requires intraoperative neurophysiological confirmation of electrode placement. Recently, purely image guided methods are being evaluated as to their clinical efficacy in comparison to surgery using microelectrode recordings. We used the ClearPoint(®) system to place electrodes in both the subthalamic nucleus and globus pallidus internus in patients with advanced Parkinson's disease. Off medication UPDRS scores were assessed before and 1 year after surgery as well as pre- and 1 year post-operative neuropsychological outcomes. Targeting precision was also assessed. Patients implanted in the subthalamic nucleus improved by 46.2 % in their UPDRS scores post-operatively (p = 0.03) whereas the globus pallidus group improved by 41 % (p = 0.06). There were no significant adverse neuropsychological outcomes in either group of patients. Mean radial error for the STN group was 1.2 ± 0.7 mm and for the GPi group 0.8 mm ± 0.3 mm. Image guided DBS using the ClearPoint(®)system has high targeting precision with robust clinical outcomes. Our data are in accord with recent studies using the same or similar technologies and provide a rationale for a large comparative study of image-guided versus microelectrode guided DBS. PMID:27126457

  14. 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

  15. 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

  16. 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

  17. 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 γ–aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8–10 rats/group), after which the animals were placed in operant chambers containing 2 levers—one used to administer water and the other to administer 15% EtOH—to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat’s left AcbSh. The animals then received 100 or 200 μA (3–4 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 μA 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

  18. A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

    PubMed Central

    Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

    2015-01-01

    Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS

  19. Supraspinal stimulation for treatment of refractory pain.

    PubMed

    Parmar, V K; Gee, L; Smith, H; Pilitsis, J G

    2014-08-01

    Refractory pain syndromes often have far reaching effects and are quite a challenge for primary care providers and specialists alike to treat. With the help of site-specific neuromodulation and appropriate patient selection these difficult to treat pain syndromes may be managed. In this article, we focus on supraspinal stimulation (SSS) for treatment of intractable pain and discuss off-label uses of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in context to emerging indications in neuromodulation. Consideration for neuromodulatory treatment begins with rigorous patient selection based on exhaustive conservative management, elimination of secondary gains, and a proper psychology evaluation. Trial stimulation prior to DBS is nearly always performed while trial stimulation prior to MCS surgery is symptom dependent. Overall, a review of the literature demonstrates that DBS should be considered for refractory conditions including nociceptive/neuropathic pain, phantom limb pain, and chronic cluster headache (CCH). MCS should be considered primarily for trigeminal neuropathic pain (TNP) and central pain. DBS outcome studies for post-stroke pain as well as MCS studies for complex regional pain syndrome (CRPS) show more modest results and are also discussed in detail. PMID:24956545

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

    PubMed

    Serranová, Tereza; Jech, Robert; Dušek, Petr; Sieger, Tomáš; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen

    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

  1. Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

    PubMed

    Jiménez-Sánchez, Laura; Linge, Raquel; Campa, Leticia; Valdizán, Elsa M; Pazos, Ángel; Díaz, Álvaro; Adell, Albert

    2016-09-01

    Deep brain stimulation (DBS) is a treatment that has shown some efficacy in treatment-resistant depression. In particular, DBS of the subcallosal cingulate gyrus (Brodmann's area 25, Cg25) has been successfully applied to treat refractory depression. In the rat, we have demonstrated that DBS applied to infralimbic (IL) cortex elevates the levels of glutamate and monoamines in the prefrontal cortex, and requires the stimulation of cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors for its antidepressant-like effects. However, the molecular targets of IL DBS are not fully known. To gain insight into these pathways, we have investigated whether IL DBS is able to reverse the behavioral, biochemical and molecular changes exhibited by the olfactory bulbectomized (OBX) rat. Our results revealed that 1 h IL DBS diminished hyperlocomotion, hyperemotionality and anhedonia, and increased social interaction shown by the OBX rats. Further, IL DBS increased prefrontal efflux of glutamate and serotonin in both sham-operated and OBX rats. With regard to molecular targets, IL DBS increases the synthesis of brain-derived neurotrophic factor (BDNF) and the GluA1 AMPA receptor subunit, and stimulates the Akt/mammalian target of rapamycin (mTOR) as well as the AMPA receptor/c-AMP response element binding (CREB) pathways. Temsirolimus, a known in vivo mTOR blocker, suppressed the antidepressant-like effect of IL DBS in naïve rats in the forced swim test, thus demonstrating for the first time that mTOR signaling is required for the antidepressant-like effects of IL DBS, which is in line with the antidepressant response of other rapid-acting antidepressant drugs. PMID:27108934

  2. Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series

    PubMed Central

    Lenartz, Doris; Kuhn, Jens; Sturm, Volker

    2016-01-01

    Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31–48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed “partial response” on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders. PMID:27504631

  3. Analysis of benzodiazepines and their metabolites using DBS cards and LC-MS/MS.

    PubMed

    Lee, Heesang; Park, Yujin; Jo, Jiyeong; In, Sangwhan; Park, Yonghoon; Kim, Eunmi; Pyo, Jaesung; Choe, Sanggil

    2015-10-01

    Dried Blood Spot (DBS) has been used a blood extraction method for inherited metabolic disorder screening since 1960s. With introduction of LC-MS/MS, not only DBS could be used to analysis drugs in small blood volume, but in various fields, such as toxicology, drug therapeutic monitoring, drug diagnostic screening, and illicit drugs. In toxicology field, many drugs (e.g. benzodiazepines, acetaminophen, small molecule drugs) have been tested with DBS. Compared with earlier blood extraction methods (SPE and LLE), DBS has lots of advantages; lower blood volume (less than 50μL), shorter analysis time caused by a more concise analysis procedure and lower cost. We optimized the DBS procedure and LC-MS/MS conditions for 18 benzodiazepines, seven benzodiazepine metabolites, and one z-drug (zolpidem) analysis in blood. 30μL of whole blood was spotted on FTA DMPK card C and dried for 2h in a desiccator. A 6-mm disk was punched and vortexed for 1min in a centrifuge tube with 300μL methanol/acetonitrile mixture (1:1, v/v). After evaporation, redissolved in 100μL mobile phase of LC-MS/MS and 5μL was injected. In the analysis for 26 target compounds in blood, all of the method validation parameters - LLOD, LLOQ, accuracy (intra- and inter-assay), and precision (intra- and inter-assay) - were satisfied with method validation criteria, within 15%. The results of matrix effect, recovery, and process efficiency were good. We developed a fast and reliable sample preparation method using DBS for 26 benzodiazepines, benzodiazepine metabolites, and z-drug (zolpidem). PMID:26255955

  4. 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

    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

  5. 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

  6. 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.

  7. Deep brain stimulation of the human reward system for major depression--rationale, outcomes and outlook.

    PubMed

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

    2014-05-01

    Deep brain stimulation (DBS) as a putative approach for treatment-resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studies--all in relatively small patient populations and different target regions-have 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 and--as a novelty--extrapolates 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

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

    PubMed

    Wagenbreth, Caroline; Zaehle, Tino; Galazky, Imke; Voges, Jürgen; Guitart-Masip, Marc; Heinze, Hans-Jochen; Düzel, 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

  9. Deep Brain Stimulation of the Human Reward System for Major Depression—Rationale, 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 studies—all in relatively small patient populations and different target regions—have 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 and—as a novelty—extrapolates 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

  10. Deep brain stimulation improves gait velocity in Parkinson's disease: a systematic review and meta-analysis.

    PubMed

    Roper, Jaimie A; Kang, Nyeonju; Ben, Juliana; Cauraugh, James H; Okun, Michael S; Hass, Chris J

    2016-06-01

    In Parkinson's disease (PD), slow gait speed is significantly related to clinical ratings of disease severity, impaired performance of daily activities, as well as increased overall disability. Conducting a meta-analysis on gait speed is an objective and quantitative technique to summarize the effectiveness of DBS and to determine the effect sizes for future studies. We conducted a systematic review and meta-analysis that analyzed the effects of deep brain stimulation (DBS) surgery on gait speed in patients with PD to gain fundamental insight into the nature of therapeutic effectiveness. A random effects model meta-analysis on 27 studies revealed a significant overall standardized mean difference medium effect size equal to 0.60 (SE = 0.06; p < 0.0001; Z = 10.58). Based on our synthesis of the 27 studies, we determined the following: (1) a significant and medium effect size indicating DBS improves gait speed; (2) DBS improved gait speed regardless of whether the patients were tested in the on or off medication state; (3) both bilateral and unilateral DBS led to gait speed improvement; (4) the effects of DBS on gait speed in the data collection sessions after surgery (DBS on vs. off) were comparable with data collection before surgery (before surgery vs. DBS after surgery); and (5) when evaluating the effects of DBS and medication on gait speed suprathreshold doses were comparable to normal dosages of medication and DBS. The current analysis provides objective evidence that both unilateral and bilateral DBS provide a therapeutic benefit on gait speed in persons with PD. PMID:27126451

  11. Flexible retinal electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.; Christenson, Todd R.

    2006-10-24

    An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

  12. Micromachined electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.

    2007-12-11

    An electrode array is disclosed which has applications for neural stimulation and sensing. The electrode array, in certain embodiments, can include a plurality of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. In other embodiments of the electrode array, the electrodes can be fixed to the substrate. The electrode array can be formed from a combination of bulk and surface micromachining, and can include electrode tips having an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis.

  13. 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…

  14. Deep-Brain Stimulation for Basal Ganglia Disorders

    PubMed Central

    Wichmann, Thomas; DeLong, Mahlon R.

    2011-01-01

    The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders. PMID:21804953

  15. Effects of thalamic deep brain stimulation on spontaneous language production.

    PubMed

    Ehlen, Felicitas; Vonberg, Isabelle; Kühn, Andrea A; Klostermann, Fabian

    2016-08-01

    The thalamus is thought to contribute to language-related processing, but specifications of this notion remain vague. An assessment of potential effects of thalamic deep brain stimulation (DBS) on spontaneous language may help to delineate respective functions. For this purpose, we analyzed spontaneous language samples from thirteen (six female / seven male) patients with essential tremor treated with DBS of the thalamic ventral intermediate nucleus (VIM) in their respective ON vs. OFF conditions. Samples were obtained from semi-structured interviews and examined on multidimensional linguistic levels. In the VIM-DBS ON condition, participants used a significantly higher proportion of paratactic as opposed to hypotactic sentence structures. This increase correlated negatively with the change in the more global cognitive score, which in itself did not change significantly. In conclusion, VIM-DBS appears to induce the use of a simplified syntactic structure. The findings are discussed in relation to concepts of thalamic roles in language-related cognitive behavior. PMID:27267813

  16. 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

  17. Restoration of segregated, physiological neuronal connectivity by desynchronizing stimulation

    NASA Astrophysics Data System (ADS)

    Hauptmann, Christian; Tass, Peter A.

    2010-10-01

    The loss of segregation of neuronal signal processing pathways is an important hypothesis for explaining the origin of functional deficits as associated with Parkinson's disease. Here we use a modeling approach which is utilized to study the influence of deep brain stimulation on the restoration of segregated activity in the target structures. Besides the spontaneous activity of the target network, the model considers a weak sensory input mimicking signal processing tasks, electrical deep brain stimulation delivered through a standard DBS electrode and synaptic plasticity. We demonstrate that the sensory input is capable of inducing a modification of the network structure which results in segregated microcircuits if the network is initialized in the healthy, desynchronized state. Depending on the strength and coverage, the sensory input is capable of restoring the functional sub-circuits even if the network is initialized in the synchronized, pathological state. Weak coordinated reset stimulation, applied to a network featuring a loss of segregation caused by global synchronization, is able to restore the segregated activity and to truncate the pathological, synchronized activity.

  18. Restoration of segregated, physiological neuronal connectivity by desynchronizing stimulation.

    PubMed

    Hauptmann, Christian; Tass, Peter A

    2010-10-01

    The loss of segregation of neuronal signal processing pathways is an important hypothesis for explaining the origin of functional deficits as associated with Parkinson's disease. Here we use a modeling approach which is utilized to study the influence of deep brain stimulation on the restoration of segregated activity in the target structures. Besides the spontaneous activity of the target network, the model considers a weak sensory input mimicking signal processing tasks, electrical deep brain stimulation delivered through a standard DBS electrode and synaptic plasticity. We demonstrate that the sensory input is capable of inducing a modification of the network structure which results in segregated microcircuits if the network is initialized in the healthy, desynchronized state. Depending on the strength and coverage, the sensory input is capable of restoring the functional sub-circuits even if the network is initialized in the synchronized, pathological state. Weak coordinated reset stimulation, applied to a network featuring a loss of segregation caused by global synchronization, is able to restore the segregated activity and to truncate the pathological, synchronized activity. PMID:20811089

  19. Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia.

    PubMed

    Bikovsky, Lior; Hadar, Ravit; Soto-Montenegro, María Luisa; Klein, Julia; Weiner, Ina; Desco, Manuel; Pascau, Javier; Winter, Christine; Hamani, Clement

    2016-09-01

    Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.e. sensorimotor gating, as reflected by disrupted prepulse inhibition (PPI), and attentional selectivity, as reflected by disrupted latent inhibition (LI). In addition, the neurocircuitry influenced by DBS was studied using FDG PET. We found that mPFC- and Nacc-DBS alleviated PPI and LI abnormalities in poly I:C offspring, whereas Nacc- but not mPFC-DBS disrupted PPI and LI in saline offspring. In saline offspring, mPFC-DBS increased metabolism in the parietal cortex, striatum, ventral hippocampus and Nacc, while reducing it in the brainstem, cerebellum, hypothalamus and periaqueductal gray. Nacc-DBS, on the other hand, increased activity in the ventral hippocampus and olfactory bulb and reduced it in the septal area, brainstem, periaqueductal gray and hypothalamus. In poly I:C offspring changes in metabolism following mPFC-DBS were similar to those recorded in saline offspring, except for a reduced activity in the brainstem and hypothalamus. In contrast, Nacc-DBS did not induce any statistical changes in brain metabolism in poly I:C offspring. Our study shows that mPFC- or Nacc-DBS delivered to the adult progeny of poly I:C treated dams improves deficits in PPI and LI. Despite common behavioral responses, stimulation in the two targets induced different metabolic effects. PMID:27302677

  20. Surgical Neuroanatomy and Programming in Deep Brain Stimulation for Obsessive Compulsive Disorder

    PubMed Central

    Morishita, Takashi; Fayad, Sarah M.; Goodman, Wayne K.; Foote, Kelly D.; Chen, Dennis; Peace, David A.; Rhoton, Albert L.; Okun, Michael S.

    2014-01-01

    Objectives Deep brain stimulation (DBS) has been established as a safe, effective therapy for movement disorders (Parkinson’s disease, essential tremor, etc.), and its application is expanding to the treatment of other intractable neuropsychiatric disorders including Depression and Obsessive-Compulsive Disorder (OCD). Several published studies have supported the efficacy of DBS for severely debilitating OCD. However, questions remain regarding the optimal anatomical target and the lack of a bedside programming paradigm for OCD DBS. Management of OCD DBS can be highly variable and is typically guided by each center’s individual expertise. In this paper, we review the various approaches to targeting and programming for OCD DBS. We also review the clinical experience for each proposed target, and discuss the relevant neuroanatomy. Methods A PubMed review was performed searching for literature on OCD DBS and included all articles published before March 2012. We included all available studies with a clear description of the anatomical targets, programming details, and the outcomes. Results Six different DBS approaches were identified. High frequency stimulation with high voltage was applied in most cases, and predictive factors for favorable outcomes were discussed in the literature. Conclusion DBS remains an experimental treatment for medication refractory OCD. Target selection and programming paradigms are not yet standardized, though, an improved understanding of the relationship between the DBS lead and the surrounding neuroanatomical structures will aid in the selection of targets and the approach to programming. We propose to form a registry to track OCD DBS cases for future clinical study design. PMID:24345303

  1. Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.

    PubMed

    King, Nathaniel O; Anderson, Collin J; Dorval, Alan D

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. PMID:26498277

  2. Pallidal stimulation for primary generalised dystonia: effect on cognition, mood and quality of life.

    PubMed

    Jahanshahi, Marjan; Torkamani, Mariam; Beigi, Mazda; Wilkinson, Leonora; Page, Donna; Madeley, Laura; Bhatia, Kailash; Hariz, Marwan; Zrinzo, Ludvic; Limousin, Patricia; Ruge, Diane; Tisch, Stephen

    2014-01-01

    We investigated the effect of pallidal deep brain stimulation (GPi-DBS) in dystonia on cognition, mood, and quality of life and also assessed if DYT1 gene status influenced cognitive outcome following GPi-DBS. Fourteen patients with primary generalized dystonia (PGD) were assessed, measuring their estimated premorbid and current IQ, memory for words and faces, and working memory, language, executive function, and sustained attention, one month before and one year or more after surgery. Changes in mood and behaviour and quality of life were also assessed. There was a significant improvement of dystonia with GPi-DBS (69 % improvement in Burke-Fahn-Marsden score, p < 0.0001). Performance on five cognitive tests either improved or declined at post-surgical follow-up. Calculation of a reliable change index suggested that deterioration in sustained attention on the PASAT was the only reliable change (worse after surgery) in cognition with GPi-DBS. DYT1 gene status did not influence cognitive outcome following GPi-DBS. Depression, anxiety and apathy were not significantly altered, and ratings of health status on the EQ5D remained unchanged. In our sample, GPi-DBS was only associated with an isolated deficit on a test of sustained attention, confirming that GPi-DBS in PGD is clinically effective and safe, without adverse effects on the main domains of cognitive function. The dissociation between GPi-DBS improving dystonia, but not having a significant positive impact on the patients' QoL, warrants further investigation. PMID:24178706

  3. Deep Brain Stimulation and Medication for Parkinsonian Tremor During Secondary Tasks

    PubMed Central

    Sturman, Molly M.; Vaillancourt, David E.; Metman, Leo Verhagen; Sierens, Diane K.; Bakay, Roy A.E.; Corcos, Daniel M.

    2008-01-01

    This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson’s disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS. PMID:17469210

  4. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    PubMed

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks. PMID:26956115

  5. [Ethical aspects of deep brain stimulation in the treatment of psychiatric disorders].

    PubMed

    Schmetz, M-K; Heinemann, T

    2010-05-01

    Deep brain stimulation (DBS) is currently being tested as a possible treatment for treatment-refractory psychiatric disorders. Besides the hope set on this new therapeutic approach of DBS, there are at the same time doubts concerning the ethical acceptability in the treatment of individuals suffering from mental disorders. Taking the therapeutic benefit of DBS into account, the manuscript analyses ethical aspects of DBS application in psychiatry. In particular, possible effects on the patient's personality and self-determination are scrutinized. It is shown that personality changes may either occur as unintended and potentially ethically troublesome side effects or may even be intended as legitimate therapy goals. The patient's self-determination may be both, endangered and supported by DBS. The ethical assessment of DBS considers therapeutic benefits, the method's minimal invasiveness and reversibility on the one hand, as well as surgery-related risks of DBS treatment, an insufficient data-base due to currently missing long-term studies and the possibility of as yet inestimable, potentially long-term effects on the patient's personality and self-determination on the other hand. The ethical balancing arrives at the conclusion that DBS may be considered as ultima ratio in the treatment of psychiatric disorders and should preferably be combined with psychosocial measures. Furthermore, a prospective scientific evaluation of the procedure should include a systematic investigation of personality changes. PMID:20422491

  6. Patients’ experiences of deep brain stimulation for Parkinson's disease: a qualitative systematic review and synthesis

    PubMed Central

    Mathers, J; Rick, C; Jenkinson, C; Garside, R; Pall, H; Mitchell, R; Bayliss, S

    2016-01-01

    Objective To review and synthesise qualitative research studies that have explored patients’ experience of deep brain stimulation (DBS) in advanced Parkinson's disease (PD). Design Systematic review and meta-synthesis of 7 original papers, using metaethnography. Setting Studies conducted in Denmark, France and Sweden. Participants 116 patients who had undergone DBS and 9 spouses of patients. Results Prior to surgery, the experience of advancing PD is one of considerable loss and a feeling of loss of control. There are significant hopes for what DBS can bring. Following surgery, a sense of euphoria is described by many, although this does not persist and there is a need for significant transitions following this. We suggest that normality as a concept is core to the experience of DBS and that a sense of control may be a key condition for normality. Experience of DBS for patients and spouses, and of the transitions that they must undertake, is influenced by their hopes of what surgery will enable them to achieve, or regain (ie, a new normality). Conclusions There is a need for further qualitative research to understand the nature of these transitions to inform how best patients and their spouses can be supported by healthcare professionals before, during and after DBS. In assessing the outcomes of DBS and other treatments in advanced PD, we should consider how to capture holistic concepts such as normality and control. Studies that examine the outcomes of DBS require longer term follow-up. PMID:27338883

  7. [The transition of deep brain stimulation from disease specific to symptom specific indications].

    PubMed

    Okun, Michael S

    2012-01-01

    The success of chronic deep brain stimulation (DBS) and electrical neuro-network modulation (ENM) to address neurological and neuropsychiatric disorders has led the Food and Drug Administration (FDA), and also other worldwide regulatory agencies to grant approval for the use of DBS in specific disorders. In the United States, DBS is FDA approved for the treatment of advanced Parkinson's disease (PD), essential tremor (ET), obsessive compulsive disorder (OCD), and for dystonia. OCD and dystonia have been approved under a mechanism referred to as a humanitarian device exemption (HDE). However, as the field of DBS and ENM evolve there has been a shift in practice patterns from targeting diseases to targeting specific and disabling symptoms. This shift has been driving interdisciplinary DBS boards to collect, and to address symptom profiles in all potential DBS candidates. Based on a specific symptom profile, a strategic and personalized medicine approach can be undertaken. The personalized approach will take into consideration the brain target, a unilateral versus a bilateral procedure, and the potential for use of more than one DBS lead per brain hemisphere. Additionally, a personalized approach to DBS will also facilitate improved pre-operative medication adjustments, as well as optimal post-operative medication, behavioral, and device management. PMID:23196455

  8. 47 CFR 73.756 - System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service. 73.756 Section 73.756 Telecommunication FEDERAL... Stations § 73.756 System specifications for double-sideband (DBS) modulated emissions in the...

  9. 47 CFR 73.756 - System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service. 73.756 Section 73.756 Telecommunication FEDERAL... Stations § 73.756 System specifications for double-sideband (DBS) modulated emissions in the...

  10. 47 CFR 73.756 - System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service. 73.756 Section 73.756 Telecommunication FEDERAL... Stations § 73.756 System specifications for double-sideband (DBS) modulated emissions in the...

  11. 47 CFR 73.756 - System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service. 73.756 Section 73.756 Telecommunication FEDERAL... Stations § 73.756 System specifications for double-sideband (DBS) modulated emissions in the...

  12. High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

    PubMed

    Chang, Andrew D; Berges, Victoria A; Chung, Sunho J; Fridman, Gene Y; Baraban, Jay M; Reti, Irving M

    2016-06-01

    Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques. PMID:26606849

  13. A Non-Invasive Imaging Approach to Understanding Speech Changes following Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Narayana, Shalini; Jacks, Adam; Robin, Donald A.; Poizner, Howard; Zhang, Wei; Franklin, Crystal; Liotti, Mario; Vogel, Deanie; Fox, Peter T.

    2009-01-01

    Purpose To explore the use of non-invasive functional imaging and “virtual” lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson’s disease. Here, we report the use of Positron Emission Tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson’s disease. Method Perceptual and acoustic speech measures as well as cerebral blood flow (CBF) during speech as measured by PET were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with that resulting from DBS on. Results Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. “Virtual” lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. Conclusions This case report provides evidence that impaired speech production accompanying STN-DBS may be resulting from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities. PMID:19029533

  14. 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...

  15. Complications of deep brain stimulation surgery.

    PubMed

    Beric, A; Kelly, P J; Rezai, A; Sterio, D; Mogilner, A; Zonenshayn, M; Kopell, B

    2001-01-01

    Although technological advances have reduced device-related complications, DBS surgery still carries a significant risk of transient and permanent complications. We report our experience in 86 patients and 149 DBS implants. Patients with Parkinson's disease, essential tremor and dystonia were treated. There were 8 perioperative, 8 postoperative, 9 hardware-related complications and 4 stimulation-induced side effects. Only 5 patients (6%) sustained some persistent neurological sequelae, however, 26 of the 86 patients undergoing 149 DBS implants in this series experienced some untoward event with the procedure. Although there were no fatalities or permanent severe disabilities encountered, it is important to extend the informed consent to include all potential complications. PMID:12378060

  16. Deep brain stimulation to reduce sexual drive

    PubMed Central

    Fuss, Johannes; Auer, Matthias K.; Biedermann, Sarah V.; Briken, Peer; Hacke, Werner

    2015-01-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  17. Novel applications of deep brain stimulation

    PubMed Central

    Sankar, Tejas; Tierney, Travis S.; Hamani, Clement

    2012-01-01

    The success of deep brain stimulation (DBS) surgery in treating medically refractory symptoms of some movement disorders has inspired further investigation into a wide variety of other treatment-resistant conditions. These range from disorders of gait, mood, and memory to problems as diverse as obesity, consciousness, and addiction. We review the emerging indications, rationale, and outcomes for some of the most promising new applications of DBS in the treatment of postural instability associated with Parkinson's disease, depression, obsessive–compulsive disorder, obesity, substance abuse, epilepsy, Alzheimer′s-type dementia, and traumatic brain injury. These studies reveal some of the excitement in a field at the edge of a rapidly expanding frontier. Much work still remains to be done on basic mechanism of DBS, optimal target and patient selection, and long-term durability of this technology in treating new indications. PMID:22826807

  18. Deep Brain Stimulation for Chronic Pain.

    PubMed

    Falowski, Steven M

    2015-07-01

    Deep brain stimulation (DBS) is a commonly performed procedure and has been used for the treatment of chronic pain since the early 1970s. A review of the literature was performed utilizing the PubMed database evaluating the use of DBS in the treatment of various pain syndromes. Literature over the last 30 years was included with a focus on those articles in the last 10 years dealing with pain conditions with the highest success as well as the targets utilized for treatment. DBS carries favorable results for the treatment of chronic pain, especially when other methods have not been successful such as medications, conservative measures, and extracranial procedures. Various chronic pain conditions reported in the literature respond to DBS including failed back surgery syndrome (FBSS), phantom limb pain, and peripheral neuropathic pain with a higher response rate for those with nociceptive pain compared to neuropathic pain. Cephaligias have promising results, with cluster headaches carrying the best success rates. DBS plays a role in the treatment of chronic pain conditions. Although considered investigational in the USA, it carries promising success rates in a recalcitrant patient population. PMID:26049773

  19. Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder.

    PubMed

    de Koning, P P; Figee, M; Endert, E; van den Munckhof, P; Schuurman, P R; Storosum, J G; Denys, D; Fliers, E

    2016-01-01

    Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus-pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS. PMID:26812043

  20. A modular 256-channel micro electrode array platform for in vitro and in vivo neural stimulation and recording: BioMEA.

    PubMed

    Charvet, G; Billoint, O; Gharbi, S; Heuschkel, M; Georges, C; Kauffmann, T; Pellissier, A; Yvert, B; Guillemaud, R

    2010-01-01

    In order to understand the dynamics of large neural networks, where information is widely distributed over thousands of cells, one of today's challenges is to successfully monitor the simultaneous activity of as many neurons as possible. This is made possible by using the Micro-Electrode Array (MEA) technology allowing neural cell culture and/or tissue slice experimentation in vitro. Thanks to development of microelectronics' technologies, a novel data acquisition system based on MEA technology has been developed, the BioMEA™. It combines the most advanced MEA biochips with integrated electronics, and a novel user-friendly software interface. To move from prototype (result of the RMNT research project NEUROCOM) to manufactured product, a number of changes have been made. Here, we present a 256-channel MEA data acquisition system with integrated electronics (BioMEA™) allowing simultaneous recording and stimulation of neural networks for in vitro and in vivo applications. This integration is a first step towards an implantable device for BCI (Brain Computer Interface) studies and neural prosthesis. PMID:21095937

  1. Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes.

    PubMed

    Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A

    2015-10-01

    Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. PMID:25491206

  2. Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes

    PubMed Central

    Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A.

    2015-01-01

    Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. PMID:25491206

  3. A study on the effect of electrical stimulation on living tissue: potential before, during and after galvanization with constant current of 20 microA through platinum electrodes.

    PubMed

    Kubota